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Sample records for non-mu opiate receptors

  1. Opiate receptors: an introduction.

    Science.gov (United States)

    Carmody, J J

    1987-02-01

    Current status of opiate receptors and their agonists is reviewed--basic aspects of receptor theory, the importance of stereospecificity in drug-receptor interactions and the role of 'second messengers' in drug action. The three classes of endogenous opioids, originating from three distinct genes, are discussed: pro-opiomelanocortin, giving rise to beta-endorphin, ACTH and various MSHs; pro-enkephalin, giving methionine enkephalin and leucine enkephalin; and prodynorphin; their anatomical distribution and the main classes of receptors with which they interact, the mu-receptor, with a high affinity for met-enkephalin and beta-endorphin (as well as morphine and dynorphin A); the delta-receptor for which the primary ligand is leu-enkephalin; and the kappa-receptor which is the main target for the dynorphins. Functional roles for endogenous opioids are considered. Essentially they are inhibitory to target neurones, depressing motor reflexes, baroreflexes and nociception. They also have roles in the response to physical and psychological stress.

  2. In vivo studies of opiate receptors

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    Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

    1984-01-01

    To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented.

  3. Imaging opiate receptors with positron emission tomography

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    Frost, J.J.; Dannals, R.F.; Ravert, H.T.; Wilson, A.A.; Wong, D.F.; Links, J.M.; Burns, H.D.; Kuhar, M.J.; Snyder, S.H.; Wagner, H.N. Jr.

    1984-01-01

    Opiate receptors exist in the mammalian brain and are thought to meditate the diverse pharmacological actions of the opiates, such as analgesia, euphoria, and sedation. The 4-carbomethoxyl derivatives of fentanyl, such as lofentanil and R31833 (4-carbomethoxyfentanyl) bind to the opiate receptor with high affinity. C-11 R31833 was synthesized by reacting C-11 methyl iodide with the appropriate carboxylate. Male ICR mice were injected intravenously with C-11 R31833 (5..mu..g/kg), killed 30 minutes later, and the brains rapidly dissected. The thalami, striata, and cerebral cortex are rich in opiate receptors, but the cerebellum contains a very low concentration of opiate receptors. The thalamus/cerebellum and striatum/cerebellum activity ratios, calculated per mg of wet tissue, were 4.1 and 5.2 respectively. Coinjection of 5mg/kg naloxone reduced the ratios to 1.1, which indicates that the preferential localization of C-11 R31833 in the thalami and striata is due to binding to opiate is due to binding to opiate receptors. A 22 kg anesthetized male baboon was imaged using the NeuroECAT after injection of 18.9 mCi of C-11 R13833 (0.50 ..mu..g/kg, specific activity 616 Ci/mmole at time of injection). From 15-70 minutes after injection preferential accumulation of activity could be seen in the thalami, caudate nuclei, and cerebral cortex and, conversely, low activity was demonstrated in the cerebellum. At one hour postinjection the maximum measured caudate/cerebellum activity ratio per pixel was 2.9. For the NeuroECAT the recovery coefficient for the baboon caudate is ca. 0.2-0.3, and therefore the actual caudate/cerebellum ratio is ca. 10-15.

  4. [Opiate receptors and endorphines (author's transl)].

    Science.gov (United States)

    Taube, H D

    1978-01-01

    Recent progress in narcotic drug research is briefly reviewed. Several investigators were able, independently to identify stereospecific opiate receptors, which mediate the specific effects of narcotic analgesics. A possible physiological importance of opiate receptors is likely, since endogenous ligands could be detected. Especially from brain and from pituitary glands of several species, quite a number of peptides with morphine-like effects could be isolated. The chemical structure of some of these endorphines could be analyzed. Endorphines are suggested to be involved in pain perception, electroanalgesia, acupuncture analgesia, psychiatric disorders, synthesis and release of pituitary hormones.

  5. Properties of Opiate-Receptor Binding in Rat Brain

    Science.gov (United States)

    Pert, Candace B.; Snyder, Solomon H.

    1973-01-01

    [3H]Naloxone, a potent opiate antagonist, binds stereospecifically to opiate-receptor sites in rat-brain tissue. The binding is time, temperature, and pH dependent and saturable with respect to [3H]naloxone and tissue concentration. The [3H]naloxone-receptor complex formation is bimolecular with a dissociation constant of 20 nM. 15 Opiate agonists and antagonists compete for the same receptors, whose density is 30 pmol/g. Potencies of opiates and their antagonists in displacing [3H]naloxone binding parallel their pharmacological potencies. PMID:4525427

  6. [Endorphines--the endogenous ligands of opiate receptors (author's transl)].

    Science.gov (United States)

    Teschemacher, H

    1978-01-01

    The demonstration of opiate receptors in the nervous tissue of vertebrates in 1973 was the starting point of an intensive search for the endogenous ligands of these receptors. During the following years, several of such "edogenous opiates", called "endorphines", were isolated from various tissues of the mammalian organism. These are peptides which are able to elicit the same effects as do opiates. Possibly, they play a role in the reaction of the organism to stress.

  7. Opiate receptor blockade on human granulosa cells inhibits VEGF release.

    Science.gov (United States)

    Lunger, Fabian; Vehmas, Anni P; Fürnrohr, Barbara G; Sopper, Sieghart; Wildt, Ludwig; Seeber, Beata

    2016-03-01

    The objectives of this study were to determine whether the main opioid receptor (OPRM1) is present on human granulosa cells and if exogenous opiates and their antagonists can influence granulosa cell vascular endothelial growth factor (VEGF) production via OPRM1. Granulosa cells were isolated from women undergoing oocyte retrieval for IVF. Complementary to the primary cells, experiments were conducted using COV434, a well-characterized human granulosa cell line. Identification and localization of opiate receptor subtypes was carried out using Western blot and flow cytometry. The effect of opiate antagonist on granulosa cell VEGF secretion was assessed by enzyme-linked immunosorbent assay. For the first time, the presence of OPRM1 on human granulosa cells is reported. Blocking of opiate signalling using naloxone, a specific OPRM1 antagonist, significantly reduced granulosa cell-derived VEGF levels in both COV434 and granulosa-luteal cells (P opiate receptors and opiate signalling in granulosa cells suggest a possible role in VEGF production. Targeting this signalling pathway could prove promising as a new clinical option in the prevention and treatment of ovarian hyperstimulation syndrome.

  8. Galanin negatively modulates opiate withdrawal via galanin receptor 1

    Science.gov (United States)

    Holmes, Fiona E.; Armenaki, Athena; Iismaa, Tiina P.; Einstein, Emily B.; Shine, John; Picciotto, Marina R.; Wynick, David; Zachariou, Venetia

    2012-01-01

    Rationale The neuropeptide galanin has been shown to modulate opiate dependence and withdrawal. These effects could be mediated via activation of one or more of three distinct G-protein coupled receptors, namely GalR1, GalR2 and GalR3. Objectives In this study, we used several transgenic mouse lines to further define the mechanisms underlying the role played by galanin and its receptors in the modulation of morphine dependence. Firstly, transgenic mice expressing β-galactosidase under the control of the galanin promoter were used to assess the regulation of galanin expression in response to chronic morphine administration and withdrawal. Next, the behavioural responses to chronic morphine administration and withdrawal were tested in mice that over-express galanin, lack the GalR1 gene or lack the GalR2 gene. Methods Transgenic and matched wild-type mice were given increasing doses of morphine followed by precipitation of withdrawal by naloxone and behavioral responses to withdrawal assessed. Results Both morphine administration and withdrawal increases galanin gene transcription in the locus coerulus (LC). Increasing galanin levels in the brain reduced signs of opiate withdrawal. Mice lacking GalR1 undergo more severe opiate withdrawal, whereas mice lacking GalR2 show no significant difference in withdrawal signs, compare to matched wild type controls. Conclusions Opiate administration and withdrawal increase galanin expression in the LC. Galanin opposes the actions of morphine which lead to opiate dependence and withdrawal, an effect that is mediated via GalR1. PMID:21969124

  9. Multiple opiate receptors in the brain of spontaneously hypertensive rats

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    Das, S.; Bhargava, H.N.

    1986-03-01

    The characteristics of ..mu.., delta and kappa -opiate receptors in the brain of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats were determined using the receptor binding assays. The ligands used were /sup 3/H-naltrexone (..mu..), /sup 3/H-ethylketocyclazocine (EKC, kappa) and /sup 3/H-Tyr-D-Ser-Gly-Phe-Leu-Thr (DSTLE, delta). Since EKC binds to ..mu.. and delta receptors in addition to kappa, the binding was done in the presence of 100 nM each of DAGO and DADLE to suppress ..mu.. and delta sites, respectively. All three ligands bound to brain membranes of WKY rats at a single high affinity site with the following B/sub max/ (fmol/mg protein) and K/sub d/ (nM) values: /sup 3/H-naltrexone (130.5; 0.43) /sup 3/H-EKC (19.8, 1.7) and /sup 3/H-DSTLE (139, 2.5). The binding of /sup 3/H-naltrexone and /sup 3/H-DSTLE in the brain of WKY and SH did not differ. A consistent increase (22%) in B/sub max/ of /sup 3/H-EKC was found in SHR compared to WKY rats. However, the K/sub d/ values did not differ. The increase in B/sub max/ was due to increases in hypothalamus and cortex. It is concluded that SH rats have higher density of kappa-opiate receptors, particularly in hypothalamus and cortex, compared to WKY rats, and that kappa-opiate receptors may be involved in the pathophysiology of hypertension.

  10. Endomorphins: novel endogenous mu-opiate receptor agonists in regions of high mu-opiate receptor density.

    Science.gov (United States)

    Zadina, J E; Martin-Schild, S; Gerall, A A; Kastin, A J; Hackler, L; Ge, L J; Zhang, X

    1999-01-01

    Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2, EM-1) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2, EM-2) are peptides recently isolated from brain that show the highest affinity and selectivity for the mu (morphine) opiate receptor of all the known endogenous opioids. The endomorphins have potent analgesic and gastrointestinal effects. At the cellular level, they activate G-proteins (35S-GTP gamma-S binding) and inhibit calcium currents. Support for their role as endogenous ligands for the mu-opiate receptor includes their localization by radioimmunoassay and immunocytochemistry in central nervous system regions of high mu receptor density. Intense EM-2 immunoreactivity is present in the terminal regions of primary afferent neurons in the dorsal horn of the spinal cord and in the medulla near high densities of mu receptors. Chemical (capsaicin) and surgical (rhizotomy) disruption of nociceptive primary afferent neurons depletes the immunoreactivity, implicating the primary afferents as the source of EM-2. Thus, EM-2 is well-positioned to serve as an endogenous modulator of pain in its earliest stages of perception. In contrast to EM-2, which is more prevalent in the spinal cord and lower brainstem, EM-1 is more widely and densely distributed throughout the brain than EM-2. The distribution is consistent with a role for the peptides in the modulation of diverse functions, including autonomic, neuroendocrine, and reward functions as well as modulation of responses to pain and stress.

  11. Alteration of dopamine receptor sensitivity by opiates and the subsequent effect of this alteration on opiate tolerance and dependence

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    Martin, J.R.

    1985-01-01

    The present study was undertaken to determine whether there is an alteration of dopamine receptor sensitivity following opiate administration, and whether this alteration has any influence on the development of opiate tolerance and dependence. Behavioral hypersensitivity to direct-acting dopamine agonists was observed in mice following acute or chronic morphine administration. Acute levorphanol administration also resulted in potentiation of dopamine agonist-induced behaviors. An increase in density of dopamine receptors, as measured by (/sup 3/H)butyrophenone binding accompanied the development of behavioral hypersensitivity. This increase was localized to the striatum, an area important in the mediation of dopamine-agonist induced behaviors. Naloxone or LiCl coadministered with the opiates prevented the development of hypersensitivity and the increase in density of dopamine receptors. Coadministration of lithium enhanced the development of acute and chronic tolerance. Lithium enhanced the development of dependence as determined by naloxone-induced hypothermia in chronically morphine-treated mice. Apomorphine enhanced naloxone-induced withdrawal in acutely dependent mice. This enhancement was blocked by coadministration of lithium with the opiates. These results suggest that dopamine receptor supersensitivity influences the degree of tolerance and dependence.

  12. CRF2 receptor-deficiency eliminates opiate withdrawal distress without impairing stress coping.

    Science.gov (United States)

    Ingallinesi, M; Rouibi, K; Le Moine, C; Papaleo, F; Contarino, A

    2012-12-01

    The opiate withdrawal syndrome is a severe stressor that powerfully triggers addictive drug intake. However, no treatment yet exists that effectively relieves opiate withdrawal distress and spares stress-coping abilities. The corticotropin-releasing factor (CRF) system mediates the stress response, but its role in opiate withdrawal distress and bodily strategies aimed to cope with is unknown. CRF-like signaling is transmitted by two receptor pathways, termed CRF(1) and CRF(2). Here, we report that CRF(2) receptor-deficient (CRF(2)(-/-)) mice lack the dysphoria-like and the anhedonia-like states of opiate withdrawal. Moreover, in CRF(2)(-/-) mice opiate withdrawal does not increase the activity of brain dynorphin, CRF and periaqueductal gray circuitry, which are major substrates of opiate withdrawal distress. Nevertheless, CRF(2) receptor-deficiency does not impair brain, neuroendocrine and autonomic stress-coping responses to opiate withdrawal. The present findings point to the CRF(2) receptor pathway as a unique target to relieve opiate withdrawal distress without impairing stress-coping abilities.

  13. Opiates modulate thermosensation by internalizing cold receptor TRPM8.

    Science.gov (United States)

    Shapovalov, George; Gkika, Dimitra; Devilliers, Maily; Kondratskyi, Artem; Gordienko, Dmitri; Busserolles, Jerome; Bokhobza, Alexandre; Eschalier, Alain; Skryma, Roman; Prevarskaya, Natalia

    2013-08-15

    Stimulation of μ-opioid receptors (OPRMs) brings powerful pain relief, but it also leads to the development of tolerance and addiction. Ensuing withdrawal in abstinent patients manifests itself with severe symptoms, including cold hyperalgesia, often preventing addicted patients from successfully completing the rehabilitation. Unsurprisingly, OPRMs have been a central point of many studies. Nonetheless, a satisfactory understanding of the pathways leading to distorted sensory responses during opiate administration and abstinence is far from complete. Here, we present a mechanism that leads to modulation by OPRMs of one of the sensory responses, thermosensation. Activation of OPRM1 leads to internalization of a cold-sensor TRPM8, which can be reversed by a follow-up treatment with the inverse OPRM agonist naloxone. Knockout of TRPM8 protein leads to a decrease in morphine-induced cold analgesia. The proposed pathway represents a universal mechanism that is probably shared by regulatory pathways modulating general pain sensation in response to opioid treatment.

  14. [Opiate receptors and endorphins at the central nervous system level].

    Science.gov (United States)

    Simon, E J

    1978-01-01

    Four years ago, sterospecific sites for the bending of opiates were discovered within the brain of animals and the human being. All of the properties of these sites are in conformity with the proposition that they are pharmacological receptors which have long been postulated for these drugs. The binding of morphine or of one of its derivatives to these sites should result in chemical or physical reactions leading to well known pharmacological responses. These reactions following the binding of drugs to the receptors are not yet known, but there is some evidence that cyclical nucleotides play a role. The affinity of a whole series of morphine derivatives, agonists and atagonists, is well correlated with their pharmacological effectiveness. In the presence of sodium salts, antagonists become more strongly bound and agonists less strongly than in the absence of sodium. The evidence is presented. This is explained by an equilibrium between two formations of the receptor: one characteristic of the absence of sodium and one of its presence. Receptors are found in the nervous system of all vertebrates and their distribution has been studied in the human brain. The regions with the highest concentration of receptors are those of the limbic system. A high level exists also in the "substantia gelatinosa" of the spinal cord, which is involved in the passage of painful messages. Study of the function of morphine receptors has led to the isolation, in animal brain, of a number of peptides with morphine properties named endorphines. The first two endorphines isolated were pentapeptides named encephalins. The properties of endorphines from the subject of several lecture in this course.

  15. Opiates Modulate Thermosensation by Internalizing Cold Receptor TRPM8

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    George Shapovalov

    2013-08-01

    Full Text Available Stimulation of μ-opioid receptors (OPRMs brings powerful pain relief, but it also leads to the development of tolerance and addiction. Ensuing withdrawal in abstinent patients manifests itself with severe symptoms, including cold hyperalgesia, often preventing addicted patients from successfully completing the rehabilitation. Unsurprisingly, OPRMs have been a central point of many studies. Nonetheless, a satisfactory understanding of the pathways leading to distorted sensory responses during opiate administration and abstinence is far from complete. Here, we present a mechanism that leads to modulation by OPRMs of one of the sensory responses, thermosensation. Activation of OPRM1 leads to internalization of a cold-sensor TRPM8, which can be reversed by a follow-up treatment with the inverse OPRM agonist naloxone. Knockout of TRPM8 protein leads to a decrease in morphine-induced cold analgesia. The proposed pathway represents a universal mechanism that is probably shared by regulatory pathways modulating general pain sensation in response to opioid treatment.

  16. Involvement of neuropeptide FF receptors in neuroadaptive responses to acute and chronic opiate treatments.

    Science.gov (United States)

    Elhabazi, K; Trigo, J M; Mollereau, C; Moulédous, L; Zajac, J-M; Bihel, F; Schmitt, M; Bourguignon, J J; Meziane, H; Petit-demoulière, B; Bockel, F; Maldonado, R; Simonin, F

    2012-01-01

    BACKGROUND AND PURPOSE Opiates remain the most effective compounds for alleviating severe pain across a wide range of conditions. However, their use is associated with significant side effects. Neuropeptide FF (NPFF) receptors have been implicated in several opiate-induced neuroadaptive changes including the development of tolerance. In this study, we investigated the consequences of NPFF receptor blockade on acute and chronic stimulation of opioid receptors in mice by using RF9, a potent and selective antagonist of NPFF receptors that can be administered systemically. EXPERIMENTAL APPROACH The effects of RF9 were investigated on opioid pharmacological responses including locomotor activity, antinociception, opioid-induced hyperalgesia, rewarding properties and physical dependence. KEY RESULTS RF9 had no effect on morphine-induced horizontal hyperlocomotion and slightly attenuated the decrease induced in vertical activity. Furthermore, RF9 dose-dependently blocked the long-lasting hyperalgesia produced by either acute fentanyl or chronic morphine administration. RF9 also potentiated opiate early analgesic effects and prevented the development of morphine tolerance. Finally, RF9 increased morphine-induced conditioned place preference without producing any rewarding effect by itself and decreased naltrexone-precipitated withdrawal syndrome following chronic morphine treatment. CONCLUSION AND IMPLICATIONS The NPFF system is involved in the development of two major undesirable effects: tolerance and dependence, which are clinically associated with prolonged exposure to opiates. Our findings suggest that NPFF receptors are interesting therapeutic targets to improve the analgesic efficacy of opiates by limiting the development of tolerance, and for the treatment of opioid dependence.

  17. Dopamine D2 receptor availability in opiate addicts at baseline and during naloxone precipitated withdrawal

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    Wang, G.J.; Volkow, N.D.; Logan, J. [Brookhaven National Lab., Upton, NY (United States)]|[SUNY, Stony Brook, NY (United States)]|[Psychiatry Services VAMC Northport, NY (United States)] [and others

    1996-05-01

    To determine if changes in dopamine activity contribute to the clinical presentation of opiate withdrawal we assessed dopamine (DA) D2 receptor availability in opiate-dependent subjects at baseline and during naloxone-precipitated withdrawal. DA D2 receptor availability was evaluated in eleven male heroine and methadone users using positron emission tomography (PET) and [11-C]raclopride and compared to eleven age matched male control subjects. Nine of the opiate-dependent subjects and two of the control were tested twice after placebo and naloxone (0.02 mg/kg) iv injection 7-10 min. prior to [11-C]raclopride. DA D2 receptor availability was measured using the ratio of the distribution volume in the region of interest (caudate, putamen and ventral striatum) to that in the cerebellum which is a function of B{sub max}/K{sub d}. DA D2 receptor availability in putamen was significantly lower in opiate-dependent subjects (3.44 {plus_minus} 0.4) than that in controls (3.97 {plus_minus} 0.45, p {ge} 0.009). Naloxone induced a short lasting withdrawal in all of the opiate-dependent subjects (79 {plus_minus} 17% of maximum withdrawal), but not in controls, with significant increase in pulse (p {le} 0.006), blood pressure (p {le} 0.0001), lacrimation (p {le} 0.01), muscle twitches (p {le} 0.01), annoyance (p {le} 0.005), anxiety (p {le} 0.0006), restlessness (p {le} 0.0005) and unhappiness (p {le} 0.001). DA D2 receptor availability in basal ganglia after naloxone administration was not different from that of baseline. These results document abnormalities in DA D2 receptors in opiate-dependent subjects. However, DA D2 availability did not change with naloxone-precipitated withdrawal.

  18. Effect of thyrotrophin releasing hormone on opiate receptors of the rat brain

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    Balashov, A.M.; Shchurin, M.R.

    1987-01-01

    It has recently been shown that the hypothalamic thyrotropin releasing hormone (TRH) has the properties of a morphine antagonist, blocking its inhibitory action on respiration and, to a lesser degree, its analgesic action. This suggests that the antagonistic effects of TRH are mediated through its interaction with opiate receptors. The aim of this paper is to study this hypothesis experimentally. Tritium-labelled enkephalins in conjunction with scintillation spectroscopy were used to assess the receptor binding behavior. The results indicate the existence of interconnections between the opiate systems and TRH. Although it is too early to reach definite conclusions on the mechanisms of this mutual influence and its physiological significance it can be tentatively suggested that TRH abolishes the pharmacological effects of morphine by modulating the functional state of opiate reception.

  19. The effect of hyperthyroidism on opiate receptor binding and pain sensitivity

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    Edmondson, E.A. (Baylor College of Medicine, Houston, TX (USA)); Bonnet, K.A.; Friedhoff, A.J. (New York Univ. School of Medicine, NY (USA))

    1990-01-01

    This study was conducted to determine the effect of thyroid hormone on opiate receptor ligand-binding and pain sensitivity. Specific opiate receptor-binding was performed on brain homogenates of Swiss-Webster mice. There was a significant increase in {sup 3}H-naloxone-binding in thyroxine-fed subjects (hyperthyroid). Scatchard analysis revealed that the number of opiate receptors was increased in hyperthyroid mice (Bmax = 0.238 nM for hyperthyroid samples vs. 0.174 nM for controls). Binding affinity was unaffected (Kd = 1.54 nM for hyperthyroid and 1.58 nM for control samples). When mice were subjected to hotplate stimulation, the hyperthyroid mice were noted to be more sensitive as judged by pain aversion response latencies which were half that of control animals. After morphine administration, the hyperthyroid animals demonstrated a shorter duration of analgesia. These findings demonstrate that thyroxine increases opiate receptor number and native pain sensitivity but decreases the duration of analgesia from morphine.

  20. Exposure to opiates in female adolescents alters mu opiate receptor expression and increases the rewarding effects of morphine in future offspring.

    Science.gov (United States)

    Vassoler, Fair M; Wright, Siobhan J; Byrnes, Elizabeth M

    2016-04-01

    Prescription opiate use and abuse has increased dramatically over the past two decades, including increased use in adolescent populations. Recently, it has been proposed that use during this critical period may affect future offspring even when use is discontinued prior to conception. Here, we utilize a rodent model to examine the effects of adolescent morphine exposure on the reward functioning of the offspring. Female Sprague Dawley rats were administered morphine for 10 days during early adolescence (post-natal day 30-39) using an escalating dosing regimen. Animals then remained drug free until adulthood at which point they were mated with naïve males. Adult offspring (F1 animals) were tested for their response to morphine-induced (0, 1, 2.5, 5, and 10 mg/kg, s.c.) conditioned place preference (CPP) and context-independent morphine-induced sensitization. Naïve littermates were used to examine mu opiate receptor expression in the nucleus accumbens and ventral tegmental area. Results indicate that F1 females whose mothers were exposed to morphine during adolescence (Mor-F1) demonstrate significantly enhanced CPP to the lowest doses of morphine compared with Sal-F1 females. There were no differences in context-independent sensitization between maternal treatment groups. Protein expression analysis showed significantly increased levels of accumbal mu opiate receptor in Mor-F1 offspring and decreased levels in the VTA. Taken together, these findings demonstrate a shift in the dose response curve with regard to the rewarding effects of morphine in Mor-F1 females which may in part be due to altered mu opiate receptor expression in the nucleus accumbens and VTA.

  1. Targeted expression of μ-opioid receptors in a subset of striatal direct-pathway neurons restores opiate reward.

    Science.gov (United States)

    Cui, Yijun; Ostlund, Sean B; James, Alex S; Park, Chang Sin; Ge, Weihong; Roberts, Kristofer W; Mittal, Nitish; Murphy, Niall P; Cepeda, Carlos; Kieffer, Brigitte L; Levine, Michael S; Jentsch, James David; Walwyn, Wendy M; Sun, Yi E; Evans, Christopher J; Maidment, Nigel T; Yang, X William

    2014-02-01

    μ-opioid receptors (MORs) are necessary for the analgesic and addictive effects of opioids such as morphine, but the MOR-expressing neuronal populations that mediate the distinct opiate effects remain elusive. Here we devised a new conditional bacterial artificial chromosome rescue strategy to show, in mice, that targeted MOR expression in a subpopulation of striatal direct-pathway neurons enriched in the striosome and nucleus accumbens, in an otherwise MOR-null background, restores opiate reward and opiate-induced striatal dopamine release and partially restores motivation to self administer an opiate. However, these mice lack opiate analgesia or withdrawal. We used Cre-mediated deletion of the rescued MOR transgene to establish that expression of the MOR transgene in the striatum, rather than in extrastriatal sites, is needed for the restoration of opiate reward. Our study demonstrates that a subpopulation of striatal direct-pathway neurons is sufficient to support opiate reward-driven behaviors and provides a new intersectional genetic approach to dissecting neurocircuit-specific gene function in vivo.

  2. Changes of epidermal mu-opiate receptor expression and nerve endings in chronic atopic dermatitis.

    Science.gov (United States)

    Bigliardi-Qi, M; Lipp, B; Sumanovski, L T; Buechner, S A; Bigliardi, P L

    2005-01-01

    There is increasing evidence that neuropeptides such as a substance P, neurotrophins or beta-endorphin, an endogenous agonist for mu-opioid receptor, are involved in the pathogenesis of atopic dermatitis in which mental stress and scratching deteriorate the disease. mu-Opioid receptor, a G-protein-coupled receptor, can be downregulated and internalized by agonists and other factors in vitro. In this study, we investigated the regulation of mu-opioid receptor and nerve endings in atopic dermatitis patients. Skin biopsies from atopic dermatitis patients revealed a significant downregulation of mu-opiate receptor expression in epidermis of atopic dermatitis. Permeabilization of the skin showed that the receptor in keratinocytes from atopic dermatitis is internalized. The mRNA expression pattern of the mu-opiate receptor is different in epidermis taken from patients with chronic atopic dermatitis compared to normal skin. In atopic dermatitis, the mRNA is concentrated in the subcorneal layers of the epidermis and in normal skin in the suprabasal layers. Staining of the nerve endings using protein gene product 9.5 shows a different pattern of epidermal nerve endings in normal skin compared to atopic dermatitis. In normal skin, the epidermal nerve endings are rather thick. However, in atopic dermatitis, the epidermal nerve endings are thin and run straight through the epidermis. Based on these observations and combining the 'intensity' and 'pattern' hypothesis, we propose a new theory especially for histamine-unrelated, peripheral induction of chronic pruritus. We suggest that 'itch' is elicited in the epidermal unmyelinated nerve C-fibers and 'pain' in the dermal unmyelinated nerve fibers. The downregulation of the opioid receptor in the epidermis contributes to the chronic itching. We call this new hypothesis the 'layer hypothesis'.

  3. 3-(/sup 18/F)Acetylcyclofoxy: a useful probe for the visualization of opiate receptors in living animals

    Energy Technology Data Exchange (ETDEWEB)

    Pert, C.B.; Danks, J.A. (National Inst. of Mental Health, Bethesda, MD (USA)); Channing, M.A.; Eckelman, W.C.; Larson, S.M.; Bennett, J.M. (National Institutes of Health, Bethesda, MD (USA)); Burke, T.R. Jr.; Rice, K.C. (National Inst. of Arthritis, Metabolism, and Digestive Diseases, Bethesda, MD (USA))

    1984-11-19

    A fluoro-analogue of the potent narcotic antagonist, naltrexone, was synthesized and shown to bind with high affinity to opiate receptors in vitro. 3-(/sup 18/F)acetylcyclofoxy was prepared via a one-step triflate displacement reaction with the positron emitting /sup 18/F ion from tetraethylammonium(/sup 18/F)fluoride. 3-(/sup 18/F)acetylcyclofoxy accumulation in opiate receptor rich brain regions of both rat and baboon is shown to be completely displaced by the active enantiomer of naloxone ((-)-naloxone) while the identical dose of the pharmacologically inert (+)-naloxone has no detectable effect. Moreover, both rat and baboon brain showed the well documented, typical opiate receptor distribution so that basal ganglia and thalamus are clearly visible in the living baboon brain up to 95 min after intravenous injection of 3-(/sup 18/F)acetylcyclofoxy.

  4. [Influence of Opiate Abuse on Expression of Toll-like Receptor 9 in Peripheral Blood Mononuclear Cells of HIV-1-Infected Individuals].

    Science.gov (United States)

    Pan, Peijiang; Wei, Fumei; Jiang, Junjun; Liang, Bingyu; Huang, Jiegang; Liao, Yanyan; Su, Jinming; Li, Yu; Yang, Xiaoyi; Chen, Hui; Ye, Li; Liang, Hao

    2015-03-01

    The aim of this study was to investigate the influence of opiate abuse on the expression of Toll-like receptor 9 (TLR9) in the peripheral blood mononuclear cells (PBMCs) of HIV-1-infected patients and to elucidate possible mechanisms involved in the enhancement of HIV-1 replication by opiate abuse. A total of 200 participants were enrolled in the study by random selection from methadone treatment centers and voluntary HIV counseling and testing centers in the cities of Nanning, Liuzhou, and Qinzhou. These participants included 50 HIV-positive opiate abusers (Opiates HIV(+) group), 50 HIV-negative opiate abusers (Opiates HIV(-) group), 50 HIV-positive subjects who were not opiate abusers (Non-opiates HIV (+) group), and 50 HIV-negative subjects who were not opiate abusers (Control group). PBMCs were isolated from the peripheral blood samples from the subjects and the expression levels of TLR9 mRNA and protein were determined by q-PCR and western blot respectively. There was no significant difference among the four groups in age, gender, nationality, domicile, marital status, educational background or duration of drug abuse (P > 0.05). The median viral loads of the Opiates HIV(+) were significantly higher than those of the Non-Opiates HIV(+) groups (4.450 x 10(3) and 3.977 x 10(3) copies/mL respectively, P Opiates HIV(+), Non-Opiates HIV(+), Opiates HIV(-) and Control groups were (2.13 +/- 1.59) x 10(-3), (3.66 +/- 2.22) x 10(-3), (1.96 +/- 1.42) x 10(-3) and (7.66 +/- 4.87) x 10(-3), respectively. The expression of TLR9 mRNA was significantly lower in both HIV-1-infected and -uninfected groups of opiate abusers compared with groups of non-abusers (P Opiates HIV(+) group and the Opiates HIV(-) group (P > 0.05). However, in the non-opiate groups, the expression levels of TLR9 mRNA in the HIV(+) group were significantly lower than that of the control group (POpiates HIV(+), Non-Opiates HIV(+), and Opiates HIV(-) groups compared to the control group. These results

  5. Mu-opiate receptor and Beta-endorphin expression in nerve endings and keratinocytes in human skin.

    Science.gov (United States)

    Bigliardi-Qi, M; Sumanovski, L T; Büchner, S; Rufli, T; Bigliardi, P L

    2004-01-01

    We have previously shown that human epidermal keratinocytes express a functionally active micro-opiate receptor, which adds a new dimension to the recently developed research in neuroimmunodermatology and neurogenic inflammation in skin diseases. Human keratinocytes specifically bind and also produce beta-endorphin, the endogenous micro-opiate receptor ligand. Using confocal imaging microscopy, we could now demonstrate that micro-opiate receptors are not only expressed in keratinocytes, but also on unmyelinated peripheral nerve fibers in the dermis and epidermis. Some of the peripheral nerve fibers also express the ligand beta-endorphin. The keratinocytes positive for beta-endorphin staining are clustered around the terminal ends of the unmyelinated nerve fibers. Therefore the opiate receptor system seems to be crucial in the direct communication between nerves and skin. The keratinocytes can influence the unmyelinated nerve fibers in the epidermis directly via secreting beta-endorphin. On the other hand, nerve fibers can also secrete beta-endorphin and influence the migration, differentiation and probably also the cytokine production pattern of keratinocytes.

  6. Synthesis and evaluation of fluorinated derivatives of fentanyl as candidates for opiate receptor studies using positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Dahren Hwang; Feliu, A.L.; Wolf, A.P.; MacGregor, R.R.; Fowler, J.S.; Arnett, C.D.

    1986-03-01

    Three fluorinated derivatives of fentanyl, fluorofentanyl (3), keto-fluorofentanyl (5), and fluorofentanol (6), were synthesized and their abilities to compete with /sup 3/diprenorphine for binding sites in guinea pig brain membranes were determined. The relative potencies were fentanyl > 3 approx.= 6 >> 5. On the basis of its apparent affinity for opiate receptors and its relative ease of synthesis, 6 was selected for further study. Fentanyl was slightly better than 6 in its ability to compete with (/sup 3/H)naltrexone for binding sites in rat brain membranes. Both fentayl and 6 exhibited a similar high ''sodium ratio'' (quotient of the IC/sub 50/'s against (/sup 3/H)naltrexone in the presence and absence of sodium chloride) generally characteristic of opiate agonists. The analgesic potencies of fentanyl and 6 were determined in rats by measuring suppression of locomotion and vocalization responses to footshock. 6 appeared slightly less potent than fentanyl, but produced a similar analgesia and catalepsy which was entirely blocked by pretreatment of rats with naloxone, an opiate antagonist. A rapid synthesis of (/sup 18/F)-6 was developed and the tissue distribution of (/sup 18/F)-6 in mice was determined 5, 60, and 120 minutes after intravenous injection. The use of this general route to /sup 18/F-labeled derivatives of fentanyl for studies of the opiate receptor using positron emission tomography is planned.

  7. Mu opioid receptor (OPRM1 as a predictor of treatment outcome in opiate-dependent individuals of Arab descent

    Directory of Open Access Journals (Sweden)

    Tay GK

    2012-09-01

    Full Text Available Laith N AL-Eitan,1 Saied A Jaradat,2 Steve YS Su,3 Guan K Tay,1 Gary K Hulse4,51Centre for Forensic Science, 2Princess Haya Biotechnology Center, Jordan University of Science and Technology, Irbid, Jordan; 3School of Mathematics and Statistics, 4School of Psychiatry and Clinical Neurosciences, 5Unit for Research and Education in Alcohol and Drugs, Queen Elizabeth II Medical Centre, The University of Western Australia, Crawley, WA, AustraliaBackground: A number of research studies on the genetics of opiate dependence have focused on the µ-opioid receptor (OPRM1, which is a primary target for opiates. This study aims to identify genetic polymorphisms within the OPRM1 gene involved in response to the biopsychosocial treatment in opiate-dependent individuals of Arab descent.Methods: Unrelated Jordanian Nationals of Arab descent (N = 183 with opiate dependence were selected for this study. These individuals, all males, met the DSM-IV criteria for opiate dependence and were undergoing a voluntary 8-week treatment program at a Jordanian Drug Rehabilitation Centre. All individuals were genotyped for 22 single nucleotide polymorphisms (SNPs within the OPRM1 gene using the Sequenom MassARRAY® system (iPLEX GOLD. Statistical analyses were carried out using the R package.Results: Patients receiving biopsychosocial treatment showed that there was a significant difference in their OPRM1 SNPs’ genotyping distribution between good, moderate, and poor responders to the treatment at two sites (rs6912029 [G-172T], and rs12205732 [G-1510A], P < 0.05, Fisher’s exact test.Conclusion: This study is the first report of an association between the OPRM1 G-172T and G-1510A polymorphisms and treatment response for opiate dependence. Specifically, this study demonstrated that the OPRM1 GG-172 and GG-1510 genotypes were more frequent among patients who were nonresponders to the biopsychosocial treatment. However, further pharmacogenetic studies in a larger cohort of

  8. Opiate-induced constipation related to activation of small intestine opioid μ2-receptors

    Institute of Scientific and Technical Information of China (English)

    Wency Chen; Hsien-Hui Chung; Juei-Tang Cheng

    2012-01-01

    AIM:To investigate the role of opioid μ-receptor subtype in opiate-induced constipation (OIC).METHODS:The effect of loperamide on intestinal transit was investigated in mice.Ileum strips were isolated from 12-wk-old male BALB/c mice for identification of isometric tension.The ileum strips were precontracted with 1 μmol/L acetylcholine (ACh).Then,decrease in muscle tone (relaxation) was characterized after cumulative administration of 0.1-10 μmol/k loperamide into the organ bath,for a concentration-dependent study.Specific blockers or antagonists were used for pretreatment to compare the changes in loperamide-induced relaxation.RESULTS:In addition to the delay in intestinal transit,loperamide produced a marked relaxation in isolated ileum precontracted with ACh,in a dose-dependent manner.This relaxation was abolished by cyprodime,a selective opioid μ-receptor antagonist,but not modified by naloxonazine at a dose sufficient to block opioid μ-1 receptors.Also,treatment with opioid μ-1 receptor agonist failed to modify the muscle tone.Moreover,the relaxation by loperamide was attenuated by glibenclamide at a dose sufficient to block ATP-sensitive K+ (KATP) channels,and by protein kinase A (PKA) inhibitor,but was enhanced by an inhibitor of phosphodiesterase for cyclic adenosine monophosphate (cAMP).CONCLUSION:Loperamide induces intestinal relaxation by activation of opioid μ-2 receptors via the cAMPPKA pathway to open KATP channels,relates to OIC.

  9. Cholecystokinin-8 suppressed /sup 3/H-etorphine binding to rat brain opiate receptors

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X.J.; Fan, S.G.; Ren, M.F.; Han, J.S.

    1989-01-01

    Radioreceptor assay (RRA) was adopted to analyze the influence of CCK-8 on /sup 3/H-etorphine binding to opiate receptors in rat brain synaptosomal membranes (P2). In the competition experiment CCK-8 suppressed the binding of /sup 3/H-etorphine. This effect was completely reversed by proglumide at 1/mu/M. Rosenthal analysis for saturation revealed two populations of /sup 3/H-etorphine binding sites. CCK-8 inhibited /sup 3/H-etorphine binding to the high affinity sites by an increase in Kd and decrease in Bmax without significant changes in the Kd and Bmax of the low affinity sites. This effect of CCK-8 was also completely reversed by proglumide at 1/mu/M. Unsulfated CCK-8 produced only a slight increase in Kd of the high affinity sites without affecting Bmax. The results suggest that CCK-8 might be capable of suppressing the high affinity opioid binding sites via the activation of CCK receptor.

  10. Dopamine receptor D1 and postsynaptic density gene variants associate with opiate abuse and striatal expression levels.

    Science.gov (United States)

    Jacobs, M M; Ökvist, A; Horvath, M; Keller, E; Bannon, M J; Morgello, S; Hurd, Y L

    2013-11-01

    Opioid drugs are highly addictive and their abuse has a strong genetic load. Dopamine-glutamate interactions are hypothesized to be important for regulating neural systems central for addiction vulnerability. Balanced dopamine-glutamate interaction is mediated through several functional associations, including a physical link between discs, large homolog 4 (Drosophila) (DLG4, PSD-95) and dopamine receptor 1 (DRD1) within the postsynaptic density to regulate DRD1 trafficking. To address whether genetic associations with heroin abuse exist in relation to dopamine and glutamate and their potential interactions, we evaluated single-nucleotide polymorphisms of key genes within these systems in three populations of opiate abusers and controls, totaling 489 individuals from Europe and the United States. Despite significant differences in racial makeup of the separate samples, polymorphisms of DRD1 and DLG4 were found to be associated with opiate abuse. In addition, a strong gene-gene interaction between homer 1 homolog (Drosophila) (HOMER1) and DRD1 was predicted to occur in Caucasian subjects. This interaction was further analyzed by evaluating DRD1 genotype in relation to HOMER1b/c protein expression in postmortem tissue from a subset of Caucasian subjects. DRD1 rs265973 genotype correlated with HOMER1b/c levels in the striatum, but not cortex or amygdala; the correlation was inversed in opiate abusers as compared with controls. Cumulatively, these results support the hypothesis that there may be significant, genetically influenced interactions between glutamatergic and dopaminergic pathways in opiate abusers.

  11. Using [(11)C]Ro15 4513 PET to characterise GABA-benzodiazepine receptors in opiate addiction: Similarities and differences with alcoholism.

    Science.gov (United States)

    Lingford-Hughes, Anne; Myers, James; Watson, Ben; Reid, Alastair G; Kalk, Nicola; Feeney, Adrian; Hammers, Alexander; Riaño-Barros, Daniela A; McGinnity, Colm J; Taylor, Lindsay G; Rosso, Lula; Brooks, David J; Turkheimer, Federico; Nutt, David J

    2016-05-15

    The importance of the GABA-benzodiazepine receptor complex and its subtypes are increasingly recognised in addiction. Using the α1/α5 benzodiazepine receptor PET radioligand [(11)C]Ro15 4513, we previously showed reduced binding in the nucleus accumbens and hippocampus in abstinent alcohol dependence. We proposed that reduced [(11)C]Ro15 4513 binding in the nucleus accumbens was a marker of addiction whilst the reduction in hippocampus and positive relationship with memory was a consequence of chronic alcohol abuse. To examine this further we assessed [(11)C]Ro15 4513 binding in another addiction, opiate dependence, and used spectral analysis to estimate contributions of α1 and α5 subtypes to [(11)C]Ro15 4513 binding in opiate and previously acquired alcohol-dependent groups. Opiate substitute maintained opiate-dependent men (n=12) underwent an [(11)C]Ro15 4513 PET scan and compared with matched healthy controls (n=13). We found a significant reduction in [(11)C]Ro15 4513 binding in the nucleus accumbens in the opiate-dependent compared with the healthy control group. There was no relationship between [(11)C]Ro15 4513 binding in the hippocampus with memory. We found that reduced [(11)C]Ro15 4513 binding was associated with reduced α5 but not α1 subtypes in the opiate-dependent group. This was also seen in an alcohol-dependent group where an association between memory performance and [(11)C]Ro15 4513 binding was primarily driven by α5 and not α1 subtype. We suggest that reduced α5 levels in the nucleus accumbens are associated with addiction since we have now shown this in dependence to two pharmacologically different substances, alcohol and opiates.

  12. Extinction of conditioned opiate withdrawal in rats is blocked by intracerebroventricular infusion of an NMDA receptor antagonist.

    Science.gov (United States)

    Coleman, Brian R; Carlezon, William A; Myers, Karyn M

    2013-04-29

    Maladaptive conditioned responses (CRs) contribute to psychiatric disorders including anxiety disorders and addiction. Methods of reducing these CRs have been considered as possible therapeutic approaches. One such method is extinction, which involves exposure to CR-eliciting cues in the absence of the event they once predicted. In animal models, extinction reduces both fear and addiction-related CRs, and in humans, extinction-based cue exposure therapy (CET) reduces fear CRs. However, CET is less effective in drug addicts, for reasons that are not clear. Increased understanding of the neurobiology of extinction of drug-related CRs as compared to fear CRs may help illuminate this issue. Here, we examine the N-methyl-d-aspartate (NMDA) receptor-dependence of extinction of conditioned opiate withdrawal in rats. Using a place conditioning paradigm, we trained morphine-dependent rats to associate an environment with naloxone-precipitated withdrawal. We then extinguished that association by returning the rats repeatedly to the environment in the absence of acute withdrawal. In some rats we administered the NMDA receptor antagonist d,l-2-amino-5-phosphovaleric acid (AP5) intracerebroventricularly immediately prior to extinction training. In a subsequent test session, these rats avoided the formerly naloxone-paired environment, similar to rats that had not undergone extinction training. By contrast, rats that received vehicle prior to extinction training did not avoid the formerly naloxone-paired environment. This finding indicates that extinction of a drug-related CR (conditioned opiate withdrawal) is dependent on NMDA receptors, similar to extinction of conditioned fear. The locus of the critical NMDA receptors is unclear but may include basolateral amygdala and/or medial prefrontal cortex.

  13. Mu opioid receptors on primary afferent nav1.8 neurons contribute to opiate-induced analgesia: insight from conditional knockout mice.

    Science.gov (United States)

    Weibel, Raphaël; Reiss, David; Karchewski, Laurie; Gardon, Olivier; Matifas, Audrey; Filliol, Dominique; Becker, Jérôme A J; Wood, John N; Kieffer, Brigitte L; Gaveriaux-Ruff, Claire

    2013-01-01

    Opiates are powerful drugs to treat severe pain, and act via mu opioid receptors distributed throughout the nervous system. Their clinical use is hampered by centrally-mediated adverse effects, including nausea or respiratory depression. Here we used a genetic approach to investigate the potential of peripheral mu opioid receptors as targets for pain treatment. We generated conditional knockout (cKO) mice in which mu opioid receptors are deleted specifically in primary afferent Nav1.8-positive neurons. Mutant animals were compared to controls for acute nociception, inflammatory pain, opiate-induced analgesia and constipation. There was a 76% decrease of mu receptor-positive neurons and a 60% reduction of mu-receptor mRNA in dorsal root ganglia of cKO mice. Mutant mice showed normal responses to heat, mechanical, visceral and chemical stimuli, as well as unchanged morphine antinociception and tolerance to antinociception in models of acute pain. Inflammatory pain developed similarly in cKO and controls mice after Complete Freund's Adjuvant. In the inflammation model, however, opiate-induced (morphine, fentanyl and loperamide) analgesia was reduced in mutant mice as compared to controls, and abolished at low doses. Morphine-induced constipation remained intact in cKO mice. We therefore genetically demonstrate for the first time that mu opioid receptors partly mediate opiate analgesia at the level of Nav1.8-positive sensory neurons. In our study, this mechanism operates under conditions of inflammatory pain, but not nociception. Previous pharmacology suggests that peripheral opiates may be clinically useful, and our data further demonstrate that Nav1.8 neuron-associated mu opioid receptors are feasible targets to alleviate some forms of persistent pain.

  14. Mu opioid receptors on primary afferent nav1.8 neurons contribute to opiate-induced analgesia: insight from conditional knockout mice.

    Directory of Open Access Journals (Sweden)

    Raphaël Weibel

    Full Text Available Opiates are powerful drugs to treat severe pain, and act via mu opioid receptors distributed throughout the nervous system. Their clinical use is hampered by centrally-mediated adverse effects, including nausea or respiratory depression. Here we used a genetic approach to investigate the potential of peripheral mu opioid receptors as targets for pain treatment. We generated conditional knockout (cKO mice in which mu opioid receptors are deleted specifically in primary afferent Nav1.8-positive neurons. Mutant animals were compared to controls for acute nociception, inflammatory pain, opiate-induced analgesia and constipation. There was a 76% decrease of mu receptor-positive neurons and a 60% reduction of mu-receptor mRNA in dorsal root ganglia of cKO mice. Mutant mice showed normal responses to heat, mechanical, visceral and chemical stimuli, as well as unchanged morphine antinociception and tolerance to antinociception in models of acute pain. Inflammatory pain developed similarly in cKO and controls mice after Complete Freund's Adjuvant. In the inflammation model, however, opiate-induced (morphine, fentanyl and loperamide analgesia was reduced in mutant mice as compared to controls, and abolished at low doses. Morphine-induced constipation remained intact in cKO mice. We therefore genetically demonstrate for the first time that mu opioid receptors partly mediate opiate analgesia at the level of Nav1.8-positive sensory neurons. In our study, this mechanism operates under conditions of inflammatory pain, but not nociception. Previous pharmacology suggests that peripheral opiates may be clinically useful, and our data further demonstrate that Nav1.8 neuron-associated mu opioid receptors are feasible targets to alleviate some forms of persistent pain.

  15. Preparation of (/sup 11/C)buprenorphine - a potential radioligand for the study of the opiate receptor system in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Luthra, S.K.; Pike, V.W.; Brady, F.; Horlock, P.L.; Prenant, C.; Crouzel, C.

    1987-01-01

    A method is described for the preparation of (/sup 11/C)buprenorphine in high specific activity, based on the reaction of N-(de-cyclopropylmethyl)buprenorphine with ''no carrier added'' (1-/sup 11/C)cyclopropanecarbonyl chloride followed by reduction with lithium aluminium hydride. The (1-/sup 11/C)cyclopropanecarbonyl chloride is itself prepared from cyclotron-produced (/sup 11/C)carbon dioxide. The overall preparation time is 57 min from the end of radionuclide production, and the radiochemical yield is ca 20%, (decay-corrected from (/sup 11/C)-carbon dioxide). (/sup 11/C)Buprenophine has potential as a radio-ligand for the study of the opiate receptor system in vivo by means of position emission tomography.

  16. GABA(B) receptor activation in the ventral tegmental area inhibits the acquisition and expression of opiate-induced motor sensitization.

    Science.gov (United States)

    Leite-Morris, Kimberly A; Fukudome, Eugene Y; Shoeb, Marwa H; Kaplan, Gary B

    2004-02-01

    Opiate-induced motor sensitization refers to the progressive and enduring motor response that develops after intermittent drug administration, and results from neuroadaptive changes in ventral tegmental area (VTA) and nucleus accumbens (NAc) neurons. Repeated activation of mu-opioid receptors localized on gamma-aminobutyric acid (GABA) neurons in the VTA enhances dopaminergic cell activity and stimulates dopamine release in the nucleus accumbens. We hypothesize that GABA(B) receptor agonist treatment in the VTA blocks morphine-induced motor stimulation, motor sensitization, and accumbal Fos immunoreactivity by inhibiting the activation of dopaminergic neurons. First, C57BL/6 mice were coadministered a single subcutaneous injection of morphine with intra-VTA baclofen, a GABA(B) receptor agonist. Baclofen produced a dose-dependent inhibition of opiate-induced motor stimulation that was attenuated by 2-hydroxysaclofen, a GABA(B) receptor antagonist. Next, morphine was administered on days 1, 3, 5, and 9 and mice demonstrated sensitization to its motor stimulant effects and concomitant induction of Fos immunoreactivity in the NAc shell (NAcS) but not NAc core. Intra-VTA baclofen administered during morphine pretreatment blocked the acquisition of morphine-induced motor sensitization and Fos activation in the NAcS. Intra-VTA baclofen administered only on day 9 blocked the expression of morphine-induced motor sensitization and Fos activation in the NAcS. A linear relationship was found between morphine-induced motor activity and accumbal Fos in single- and repeated-dose treatment groups. In conclusion, GABA(B) receptor stimulation in the VTA blocked opiate-induced motor stimulation and motor sensitization by inhibiting the activation of NAcS neurons. GABA(B) receptor agonists may be useful pharmacological treatments in altering the behavioral effects of opiates.

  17. Different expression of mu-opiate receptor in chronic and acute wounds and the effect of beta-endorphin on transforming growth factor beta type II receptor and cytokeratin 16 expression.

    Science.gov (United States)

    Bigliardi, P L; Sumanovski, L T; Büchner, S; Rufli, T; Bigliardi-Qi, M

    2003-01-01

    There is evidence that neuropeptides, especially the opiate receptor agonists, are involved in wound healing. We have previously observed that beta-endorphin, the endogenous ligand for the mu-opiate receptor, stimulates the expression of cytokeratin 16 in a dose-dependent manner in human skin organ cultures. Cytokeratin 16 is expressed in hyperproliferative epidermis such as psoriasis and wound healing. Therefore we were interested to study whether epidermal mu-opiate receptor expression is changed at the wound margins in acute and chronic wounds. Using classical and confocal microscopy, we were able to compare the expression level of mu-opiate receptors and the influence of beta-endorphin on transforming growth factor beta type II receptor in organ culture. Our results show indeed a significantly decreased expression of mu-opiate receptors on keratinocytes close to the wound margin of chronic wounds compared to acute wounds. Additionally beta-endorphin upregulates the expression of transforming growth factor beta type II receptor in human skin organ cultures. These results suggest a crucial role of opioid peptides not only in pain control but also in wound healing. Opioid peptides have already been used in animal models in treatment of wounds; they induce fibroblast proliferation and growth of capillaries, and accelerate the maturation of granulation tissue and the epithelization of the defect. Furthermore opioid peptides may fine-tune pain and the inflammatory response while healing takes place. This new knowledge could potentially be used to design new locally applied drugs to improve the healing of painful chronic wounds.

  18. Endogenous opiates and behavior: 2014.

    Science.gov (United States)

    Bodnar, Richard J

    2016-01-01

    This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (endogenous opioids and receptors), and the roles of these opioid peptides and receptors in pain and analgesia (pain and analgesia); stress and social status (human studies); tolerance and dependence (opioid mediation of other analgesic responses); learning and memory (stress and social status); eating and drinking (stress-induced analgesia); alcohol and drugs of abuse (emotional responses in opioid-mediated behaviors); sexual activity and hormones, pregnancy, development and endocrinology (opioid involvement in stress response regulation); mental illness and mood (tolerance and dependence); seizures and neurologic disorders (learning and memory); electrical-related activity and neurophysiology (opiates and conditioned place preferences (CPP)); general activity and locomotion (eating and drinking); gastrointestinal, renal and hepatic functions (alcohol and drugs of abuse); cardiovascular responses (opiates and ethanol); respiration and thermoregulation (opiates and THC); and immunological responses (opiates and stimulants). This paper is the thirty-seventh consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2014 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular

  19. Presynaptic. cap alpha. -adrenoceptors and opiate receptors: inhibition of (/sup 3/H)noradrenaline release from rat cerebral cortex slices by different mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Schoffelmeer, A.N.M.; Mulder, A.H. (Vrije Univ., Amsterdam (Netherlands))

    1982-04-23

    The inhibitory effects of morphine and Cd/sup 2 +/ on electrically evoked (/sup 3/H)noradrenaline release from superfused brain slices were unaffected when release was enhanced by increasing the pulse duration, while the inhibitory effect of noradrenaline and the enhancing effect of phentolamine were diminished. A similar enhancement of (/sup 3/H)noradrenaline release by 4-aminopyridine reduced the modulatory effects of all drugs examined. Therefore there seem to be different mechanisms for the effect of presynaptic ..cap alpha..-adrenoceptors and opiate receptors on the availability of Ca/sup 2 +/ for the stimulus-secretion coupling process in noradrenergic nerve terminals.

  20. Intracerebroventricular injection of mu- and delta-opiate receptor antagonists block 60 Hz magnetic field-induced decreases in cholinergic activity in the frontal cortex and hippocampus of the rat.

    Science.gov (United States)

    Lai, H; Carino, M

    1998-01-01

    In previous research, we have found that acute exposure to a 60 Hz magnetic field decreased cholinergic activity in the frontal cortex and hippocampus of the rat as measured by sodium-dependent high-affinity choline uptake activity. We concluded that the effect was mediated by endogenous opioids inside the brain because it could be blocked by pretreatment of rats before magnetic field exposure with the opiate antagonist naltrexone, but not by the peripheral antagonist naloxone methiodide. In the present study, the involvement of opiate receptor subtypes was investigated. Rats were pretreated by intracerebroventricular injection of the mu-opiate receptor antagonist, beta-funaltrexamine, or the delta-opiate receptor antagonist, naltrindole, before exposure to a 60 Hz magnetic field (2 mT, 1 hour). It was found that the effects of magnetic field on high-affinity choline uptake in the frontal cortex and hippocampus were blocked by the drug treatments. These data indicate that both mu- and delta-opiate receptors in the brain are involved in the magnetic field-induced decreases in cholinergic activity in the frontal cortex and hippocampus of the rat.

  1. The neurobiology of opiate motivation.

    Science.gov (United States)

    Ting-A-Kee, Ryan; van der Kooy, Derek

    2012-10-01

    Opiates are a highly addictive class of drugs that have been reported to possess both dopamine-dependent and dopamine-independent rewarding properties. The search for how, if at all, these distinct mechanisms of motivation are related is of great interest in drug addiction research. Recent electrophysiological, molecular, and behavioral work has greatly improved our understanding of this process. In particular, the signaling properties of GABA(A) receptors located on GABA neurons in the ventral tegmental area (VTA) appear to be crucial to understanding the interplay between dopamine-dependent and dopamine-independent mechanisms of opiate motivation.

  2. Radiosynthesis of an opiate receptor-binding radiotracer for positron emission tomography: (C-11 methyl)-methyl-4-(N-(1-oxopropyl)-N-phenylamino)-4-piperidine carboxylate (C-11 4-carbomethoxyfentanyl)

    Energy Technology Data Exchange (ETDEWEB)

    Dannals, R.F.; Ravert, H.T.; Frost, J.J.; Wilson, A.A.; Burns, H.D.; Wagner, H.N. Jr.

    1984-01-01

    The development of high affinity, high specific activity tritium-labeled neurotransmitter receptor ligands has made it possible to determine the spatial distribution and relative regional concentration of several neuroreceptors by means of in vivo receptor labeling techniques in animals. This development made possible the biochemical identification of opiate receptors by autoradiographic visualization in experimental animals. The quantitation and localization of opiate receptors in man using non-invasive methods, such as positron emission tomography, could provide a means of obtaining information about a variety of receptor-linked neuropsychiatric diseases as well as normal brain mechanisms regulating pain and emotions. As part of a continuing program to identify and radiolabel high affinity, highly specific ligands for the opiate receptor, the authors have selected two derivatives of fentanyl, a well-known analgesic, as candidates for radiolabeling: R-31,833 (4-carbomethoxy-fentanyl) and R-34,995 (lofentanil). Carbon-11 labeled R-31,833 was synthesized by the methylation of the appropriate carboxylate with C-11 methyl iodide in dimethylformamide at room temperature and purified by high performance liquid chromatography. The average synthesis time from end-of-bombardment (E.O.B.) was 30 minutes. The average specific activity was determined by ultraviolet spectroscopy to be 890 mCi/..mu..mole end-of-synthesis (approx. 2500 mCi/..mu..mole E.O.B.).

  3. Buprenorphine in the treatment of opiate dependence: its pharmacology and social context of use in the U.S.

    Science.gov (United States)

    Wesson, Donald R

    2004-05-01

    Buprenorphine's physiological effects are produced when it attaches to specific opiate receptors that are designated mu, kappa, or delta. Buprenorphine, a partial agonist at the mu receptor and an antagonist at the kappa receptor, produces typical morphine-like effects at low doses. At higher doses, it produces opiate effects that are less than those of full opiate agonists. Knowledge of the physiological effects of opiate receptors and the way they interact with opiate agonists, partial opiate agonists, and opiate antagonists is fundamental to understanding the safety and efficacy of buprenorphine in treatment of pain and opiate addiction. Knowledge of the historical and social context of opiate agonist treatment of opiate dependence is fundamental to understanding how nonpharmacological factors may limit the clinical adoption and utility of a safe and effective medication in treatment of opiate dependence. This article reviews the pharmacology of sublingual buprenorphine and the historical context of opiate agonist therapy; delineates classes of opiate receptors and their interaction with opiate agonists, partial agonists, and antagonists; and describes the commercially available pharmaceutical formulations of buprenorphine. It focuses on sublingual buprenorphine tablets, Subutex and Suboxone, the FDA-approved formulations of buprenorphine for treatment of opiate dependence. Sublingual buprenorphine, and the combination of sublingual buprenorphine/naloxone, have unique pharmacological properties that make them a logical first-line intervention in the treatment of opioid dependence.

  4. Synthesis and evaluation of aryl-naloxamide opiate analgesics targeting truncated exon 11-associated μ opioid receptor (MOR-1) splice variants.

    Science.gov (United States)

    Majumdar, Susruta; Subrath, Joan; Le Rouzic, Valerie; Polikar, Lisa; Burgman, Maxim; Nagakura, Kuni; Ocampo, Julie; Haselton, Nathan; Pasternak, Anna R; Grinnell, Steven; Pan, Ying-Xian; Pasternak, Gavril W

    2012-07-26

    3-Iodobenzoylnaltrexamide 1 (IBNtxA) is a potent analgesic acting through a novel receptor target that lack many side-effects of traditional opiates composed, in part, of exon 11-associated truncated six transmembrane domain MOR-1 (6TM/E11) splice variants. To better understand the SAR of this drug target, a number of 4,5-epoxymorphinan analogues were synthesized. Results show the importance of a free 3-phenolic group, a phenyl ring at the 6 position, an iodine at the 3'or 4' position of the phenyl ring, and an N-allyl or c-propylmethyl group to maintain high 6TM/E11 affinity and activity. 3-Iodobenzoylnaloxamide 15 (IBNalA) with a N-allyl group displayed lower δ opioid receptor affinity than its naltrexamine analogue, was 10-fold more potent an analgesic than morphine, elicited no respiratory depression or physical dependence, and only limited inhibition of gastrointestinal transit. Thus, the aryl-naloxamide scaffold can generate a potent analgesic acting through the 6TM/E11 sites with advantageous side-effect profile and greater selectivity.

  5. Preoperative ultra-rapid opiate detoxification for the treatment of post-operative surgical pain.

    Science.gov (United States)

    Blum, James M; Biel, Sarang S; Hilliard, Paul E; Jutkiewicz, Emily M

    2015-06-01

    Over the past two decades, the prescription of high dose opiate therapy has continued to accelerate in an attempt to treat patients with chronic pain. This presents a substantial challenge when patients on high dose opiate therapy require surgery, as opiate pain relief is a cornerstone of postoperative pain management. These patients have exceptionally challenging pain to control. This is likely due to downregulation of existing opiate receptors and the reluctance of clinicians to increase doses of opiates to exceptionally high levels to facilitate pain relief. We hypothesize that using the method of ultra-rapid opiate detoxification (UROD), it would be possible to rapidly increase the number of opiate receptors and return patients to a more naive state, which would be susceptible to exogenous opiate administration. Validation of this hypothesis is supported by two mechanisms, the first of which are reports of patients that underwent UROD for opiate addition that subsequently suffer respiratory arrests when beginning to rapidly abuse opiates shortly after treatment. Additionally there are data demonstrating the tapering of opiate therapy prior to elective surgery results in better pain control. In conclusion, we hypothesize that patients on chronic high dose opiates could obtain substantially better pain relief if they underwent UROD prior to surgery. This technique could be administered shortly before surgery and may dramatically improve the patients' recoveries.

  6. Opiate drug use and the pathophysiology of neuroAIDS.

    Science.gov (United States)

    Hauser, Kurt F; Fitting, Sylvia; Dever, Seth M; Podhaizer, Elizabeth M; Knapp, Pamela E

    2012-07-01

    Opiate abuse and HIV-1 have been described as interrelated epidemics, and even in the advent of combined anti-retroviral therapy, the additional abuse of opiates appears to result in greater neurologic and cognitive deficits. The central nervous system (CNS) is particularly vulnerable to interactive opiate-HIV-1 effects, in part because of the unique responses of microglia and astroglia. Although neurons are principally responsible for behavior and cognition, HIV-1 infection and replication in the brain is largely limited to microglia, while astroglia and perhaps glial progenitors can be latently infected. Thus, neuronal dysfunction and injury result from cellular and viral toxins originating from HIV-1 infected/exposed glia. Importantly, subsets of glial cells including oligodendrocytes, as well as neurons, express µ-opioid receptors and therefore can be direct targets for heroin and morphine (the major metabolite of heroin in the CNS), which preferentially activate µ-opioid receptors. This review highlights findings that neuroAIDS is a glially driven disease, and that opiate abuse may act at multiple glial-cell types to further compromise neuron function and survival. The ongoing, reactive cross-talk between opiate drug and HIV-1 co-exposed microglia and astroglia appears to exacerbate critical proinflammatory and excitotoxic events leading to neuron dysfunction, injury, and potentially death. Opiates enhance synaptodendritic damage and a loss of synaptic connectivity, which is viewed as the substrate of cognitive deficits. We especially emphasize that opioid signaling and interactions with HIV-1 are contextual, differing among cell types, and even within subsets of the same cell type. For example, astroglia even within a single brain region are heterogeneous in their expression of µ-, δ-, and κ-opioid receptors, as well as CXCR4 and CCR5, and Toll-like receptors. Thus, defining the distinct targets engaged by opiates in each cell type, and among brain

  7. Distribution of opiate alkaloids in brain tissue of experimental animals.

    Science.gov (United States)

    Djurendic-Brenesel, Maja; Pilija, Vladimir; Mimica-Dukic, Neda; Budakov, Branislav; Cvjeticanin, Stanko

    2012-12-01

    The present study examined regional distribution of opiate alkaloids from seized heroin in brain regions of experimental animals in order to select parts with the highest content of opiates. Their analysis should contribute to resolve causes of death due to heroin intake. The tests were performed at different time periods (5, 15, 45 and 120 min) after male and female Wistar rats were treated with seized heroin. Opiate alkaloids (codeine, morphine, acetylcodeine, 6-acetylmorphine and 3,6-diacetylmorphine) were quantitatively determined in brain regions known for their high concentration of µ-opiate receptors: cortex, brainstem, amygdala and basal ganglia, by using gas chromatography-mass spectrometry (GC-MS). The highest content of opiate alkaloids in the brain tissue of female animals was found 15 min and in male animals 45 min after treatment. The highest content of opiates was determined in the basal ganglia of the animals of both genders, indicating that this part of brain tissue presents a reliable sample for identifying and assessing contents of opiates after heroin intake.

  8. A thalamic input to the nucleus accumbens mediates opiate dependence.

    Science.gov (United States)

    Zhu, Yingjie; Wienecke, Carl F R; Nachtrab, Gregory; Chen, Xiaoke

    2016-02-11

    Chronic opiate use induces opiate dependence, which is characterized by extremely unpleasant physical and emotional feelings after drug use is terminated. Both the rewarding effects of a drug and the desire to avoid withdrawal symptoms motivate continued drug use, and the nucleus accumbens is important for orchestrating both processes. While multiple inputs to the nucleus accumbens regulate reward, little is known about the nucleus accumbens circuitry underlying withdrawal. Here we identify the paraventricular nucleus of the thalamus as a prominent input to the nucleus accumbens mediating the expression of opiate-withdrawal-induced physical signs and aversive memory. Activity in the paraventricular nucleus of the thalamus to nucleus accumbens pathway is necessary and sufficient to mediate behavioural aversion. Selectively silencing this pathway abolishes aversive symptoms in two different mouse models of opiate withdrawal. Chronic morphine exposure selectively potentiates excitatory transmission between the paraventricular nucleus of the thalamus and D2-receptor-expressing medium spiny neurons via synaptic insertion of GluA2-lacking AMPA receptors. Notably, in vivo optogenetic depotentiation restores normal transmission at these synapses and robustly suppresses morphine withdrawal symptoms. This links morphine-evoked pathway- and cell-type-specific plasticity in the paraventricular nucleus of the thalamus to nucleus accumbens circuit to opiate dependence, and suggests that reprogramming this circuit holds promise for treating opiate addiction.

  9. Opiate addiction - current trends and treatment options

    Directory of Open Access Journals (Sweden)

    Achal Bhatt

    2016-07-01

    Full Text Available Opioids are widely used drugs for treatment of pain and related disorders. Opiate addiction is a major public health concern in the United States causing significant increase in healthcare expenditure. They produce euphoria and sense of well-being which makes them addictive to some people. Used in higher doses they can lead to cardiac or respiratory compromise. They also impair cognition leading to impaired decision making. Opioids exert their effects by acting on three different types of receptors mu, delta, and kappa located on neuronal cell membranes causing inhibition of neurotransmitter release. Prolonged use of these drugs can lead to physical dependence causing withdrawal symptoms if a person stops using them. Commonly used medications to treat opiate addiction are methadone, LAAM (longer acting derivative of methadone, buprenorphine, and naltrexone. [Int J Res Med Sci 2016; 4(7.000: 2503-2507

  10. Genetics of opiate addiction.

    Science.gov (United States)

    Reed, Brian; Butelman, Eduardo R; Yuferov, Vadim; Randesi, Matthew; Kreek, Mary Jeanne

    2014-11-01

    Addiction to MOP-r agonists such as heroin (and also addiction to prescription opioids) has reemerged as an epidemic in the twenty first century, causing massive morbidity. Understanding the genetics contributing to susceptibility to this disease is crucial for the identification of novel therapeutic targets, and also for discovery of genetic markers which would indicate relative protection or vulnerability from addiction, and relative responsiveness to pharmacotherapy. This information could thus eventually inform clinical practice. In this review, we focus primarily on association studies of heroin and opiate addiction, and further describe the studies which have been replicated in this field, and are thus more likely to be useful for translational efforts.

  11. Personality dimensions of opiate addicts.

    Science.gov (United States)

    Vukov, M; Baba-Milkic, N; Lecic, D; Mijalkovic, S; Marinkovic, J

    1995-02-01

    A survey of 80 opiate addicts included in a detoxification program was conducted at the Institute on Addictions in Belgrade. In addition to a dependence diagnosis and mental disorders based on DSM-III-R, we applied a Tridimensional Personality Questionnaire (TPQ) that measures the 3 major personality dimensions: novelty-seeking (NS), harm avoidance (HA) and reward dependence (RD). When compared with a control group (a sample of Yugoslav undergraduate students), the opiate addicts demonstrate significantly high NS dimension as well as significant divergences of HA and RD subscales. The surveyed opiate addicts demonstrate a high percentage of personality disorders specifically in cluster B. The personality dimensions of opiate addicts showed certain temperament traits, such as: impulsiveness, shyness with strangers, fear of uncertainty and dependence. NS, HA and RD determined by temperament specifics may be an etiological factor in forming of a personality disorder, an affective disorder as well as of a drug choice.

  12. Effects of opiates and HIV proteins on neurons: the role of ferritin heavy chain and a potential for synergism.

    Science.gov (United States)

    Festa, Lindsay; Meucci, Olimpia

    2012-07-01

    Human immunodeficiency virus 1 (HIV-1) and its associated proteins can have a profound impact on the central nervous system. Co-morbid abuse of opiates, such as morphine and heroin, is often associated with rapid disease progression and greater neurological dysfunction. The mechanisms by which HIV proteins and opiates cause neuronal damage on their own and together are unclear. The emergence of ferritin heavy chain (FHC) as a negative regulator of the chemokine receptor CXCR4, a co-receptor for HIV, may prove to be important in elucidating the interaction between HIV proteins and opiates. This review summarizes our current knowledge of central nervous system damage inflicted by HIV and opiates, as well as the regulation of CXCR4 by opiate-induced changes in FHC protein levels. We propose that HIV proteins and opiates exhibit an additive or synergistic effect on FHC/CXCR4, thereby decreasing neuronal signaling and function.

  13. Neuroscience of opiates for addiction medicine: From stress-responsive systems to behavior.

    Science.gov (United States)

    Zhou, Yan; Leri, Francesco

    2016-01-01

    Opiate addiction, similarly to addiction to other psychoactive drugs, is chronic relapsing brain disease caused by drug-induced short-term and long-term neuroadaptations at the molecular, cellular, and behavioral levels. Preclinical research in laboratory animals has found important interactions between opiate exposure and stress-responsive systems. In this review, we will discuss the dysregulation of several stress-responsive systems in opiate addiction: vasopressin and its receptor system, endogenous opioid systems (including proopiomelanocortin/mu opioid receptor and dynorphin/kappa opioid receptor), orexin and its receptor system, and the hypothalamic-pituitary-adrenal axis. A more complete understanding of how opiates alter these stress systems, through further laboratory-based studies, is required to identify novel and effective pharmacological targets for the long-term treatment of heroin addiction.

  14. [Ultra-fast opiate detoxification under general anesthesia: preliminary results of the Liege protocol].

    Science.gov (United States)

    Pinto, E; Reggers, J; Delhez, M; Fuchs, S; Venneman, I; Lamy, M; Ansseau, M

    2001-08-01

    Many studies support the hypothesis of a substantial benefit in inducing an Opiate Receptor Blockade through a Rapid Opiate Detoxification under general Anaesthesia (RODA) in opiate dependent patients. However, prospective studies and long term evaluation of the technique are lacking. In order to evaluate long-term abstinence rates after a RODA among a sample of opiate addicts, a study was started in March 1999 at the University of Liège. To date, 45 patients were evaluated (mean age: 29 +/- 5 years) with a mean opiate dependence duration of 8 +/- 4 years. Most of them were both heroin and methadone dependent; 42.2% of them were included while 31.1% did not complete the whole inclusion procedure and 26.7% were excluded. None experienced severe withdrawal symptoms. At six months, abstinence rate was 67% and 46% at one year. These preliminary results suggest the interest of the procedure in carefully selected patients.

  15. [Social cognition in opiate addicts].

    Science.gov (United States)

    Martin-Contero, M C; Secades-Villa, R; Tirapu-Ustarroz, J

    2012-12-16

    INTRODUCTION. Research on the emotional and social disorders associated with drug addiction has been very limited. AIM. To assess different components of social cognition: perception of emotional expressions, emotional-social intelligence, and empathy, in a sample of opiate addicts in a methadone maintenance program (MMP). SUBJECTS AND METHODS. Eighteen opiate addicts MMP and eighteen healthy controls participated. The test of emotional facial expression recognition, the TMMS-24, the EQ-i Bar-On, and Greene moral dilemmas were applied to each subject. RESULTS. The utilitarian response rate in impersonal moral dilemmas was significantly higher in the group of opiate dependents than in the control group. In the general and factorial social-emotional intelligence, opiate dependent group had significantly lower scores than the control group. However, they had worse facial expression recognition, nor worse scores on all three dimensions of emotional intelligence as measured by the TMMS-24. CONCLUSIONS. The opiate addicts not show a generalized deficit of social cognition, however obtain lower emotional-social intelligence quotient, and differ in empathy measured by moral judgments.

  16. Effects of Opiates and HIV Proteins on Neurons: The Role of Ferritin Heavy Chain and a Potential for Synergism

    OpenAIRE

    Festa, Lindsay; Meucci, Olimpia

    2012-01-01

    Human immunodeficiency virus 1 (HIV-1) and its associated proteins can have a profound impact on the central nervous system. Co-morbid abuse of opiates, such as morphine and heroin, is often associated with rapid disease progression and greater neurological dysfunction. The mechanisms by which HIV proteins and opiates cause neuronal damage on their own and together are unclear. The emergence of ferritin heavy chain (FHC) as a negative regulator of the chemokine receptor CXCR4, a co-receptor f...

  17. [{sup 11}C]-GR89696, a potent kappa opiate receptor radioligand; in vivo binding of the R and S enantiomers

    Energy Technology Data Exchange (ETDEWEB)

    Ravert, Hayden T. E-mail: htr@jhu.edu; Scheffel, Ursula; Mathews, William B.; Musachio, John L.; Dannals, Robert F

    2002-01-01

    The R and S enantiomers of [{sup 11}C]GR89696, [{sup 11}C]-methyl 4-[(3,4-dichlorophenyl)acetyl]-3-[(1-pyrrolidinyl)methyl] -1-piperazinecarboxylate, were synthesized from their appropriate chiral precursors and [{sup 11}C]methyl chloroformate. The [{sup 11}C]-labeled R enantiomer of GR89696, also known as GR103545, demonstrated high affinity in mouse brain with region to cerebellar ratios at 90 minutes of 11.4 and 8.7 for the hypothalamus and olfactory tubercle, respectively. The [{sup 11}C]-labeled S enantiomer showed low affinity and region to cerebellar ratios of 1 for all brain regions. The [{sup 11}C]-labeled GR103545 exhibited a selective and saturable binding for the kappa opioid receptor.

  18. Effect of Pharmacological Modulation of the Endocannabinoid System on Opiate Withdrawal: A Review of the Preclinical Animal Literature.

    Science.gov (United States)

    Wills, Kiri L; Parker, Linda A

    2016-01-01

    Over the years, animal studies have revealed a role for the endocannabinoid system in the regulation of multiple aspects of opiate addiction. The current review provides an overview of this literature in regards to opiate withdrawal. The opiate withdrawal syndrome, hypothesized to act as a negative reinforcer in mediating continued drug use, can be characterized by the emergence of spontaneous or precipitated aversive somatic and affective states following the termination of drug use. The behaviors measured to quantify somatic opiate withdrawal and the paradigms employed to assess affective opiate withdrawal (e.g., conditioned place aversion) in both acutely and chronically dependent animals are discussed in relation to the ability of the endocannabinoid system to modulate these behaviors. Additionally, the brain regions mediating somatic and affective opiate withdrawal are elucidated with respect to their modulation by the endocannabinoid system. Ultimately, a review of these findings reveals dissociations between the brain regions mediating somatic and affective opiate withdrawal, and the ability of cannabinoid type 1 (CB1) receptor agonism/antagonism to interfere with opiate withdrawal within different brain sub regions.

  19. Opiate and Cocaine Exposed Newborns: Growth Outcomes.

    Science.gov (United States)

    Butz, Arlene M.; Kaufmann, Walter E.; Royall, Richard; Kolodner, Ken; Pulsifer, Margaret B.; Lears, Mary Kathleen; Henderson, Robin; Belcher, Harolyn; Sellers, Sherri; Wilson, Modena

    1999-01-01

    Examines growth parameters at birth in 204 infants born to mothers who used cocaine and/or opiates during pregnancy. Outcome measures included birth weight, length, and head circumference. Study provides support that in utero cocaine exposure may confer more risk for somatic growth retardation at birth than opiate exposure. (Author/GCP)

  20. 阿片受体PET显像剂11C-卡芬太尼的制备及其生物学分布%Synthesis of opiate receptor radioligand 11C-carfentanil and its biodistribution in rats

    Institute of Scientific and Technical Information of China (English)

    王慧春; 管一晖; 张政伟; 刘平; 薛方平; 谭海波; 左传涛; 华逢春; 黄喆慜; 赵军

    2011-01-01

    Objective To establish an automatic synthesis method for 11C-carfentanil (CFN) as an novel opiate receptor radioligand and study its biodistribution in rats. Methods 11C-Triflate-CH3 was bubbled into 0.5 mg precursor desmethyl-CFN (which was dissolved in 0.15 ml DMSO) to generate 11C-CFN in a V-tube at room temperature. Sep-Pak C2 column was used for purification of 11C-CFN, which was eluted by 3ml binary system aqueous solution, 10 ml water thrice, and then I ml ethanol. The biodistribution (% ID/g) of 11C-CFN in SD rats was studied. SPSS 13.0 was used for statistical analysis. Non-normal distribution data were analyzed using nonparametric test. Results The synthesis time for 11C-CFN was 20 min (end of bombardment, EOB). The synthesis yield was (35.5 ± 2.2) % on average (n = 12, uncorrected)with the radiochemical purity over 98%. Biodistribution study in rats showed that the tracer had a high brain uptake, rapid blood clearance, and a metabolic pathway via liver and kidney. The highest tracer uptake was in thalamus (4.26 ± 0.89) % ID/g and striatum (4.05 ± 1.08) % ID/g at 5 min after injection, followed by cerebral cortex (2.63±0.89) %ID/g, pons (2.26 ±0.57) % ID/g, hippocampus (2. 17 ±0.55) %ID/g and cerebellum (2. 15 ±0.39) %ID/g. Conclusions The automatic synthesis of 11C-CFN is fast and reliable, and this radioligand can be used for opiate receptor imaging.%目的 建立应用国产11C模块自动化制备阿片受体PET显像剂11C-卡芬太尼(CFN)的方法,研究其在大鼠体内的生物学分布.方法 11C-碘代甲烷(CH3I)在线转化为11C-三氟甲基磺酰甲烷(Triflate-CH3),后者通入装有0.5 mg前体去甲基卡芬太尼(溶解于0.15 ml二甲基亚砜溶液)的Ⅴ型瓶内,在常温下对前体进行甲基化反应并完成11C标记,使用Sep-Pak C2柱纯化产物.正常SD大鼠尾静脉注入11C-CFN后5,15,30,45 min处死,研究其体内生物学分布,以%ID/g表示.采用SPSS 13.0软件,非正态分布资料各组间均数比

  1. Opiate modification of intracranial self-stimulation in the rat.

    Science.gov (United States)

    Weibel, S L; Wolf, H H

    1979-01-01

    Studies were conducted to confirm the involvement of central opiate receptors in the expression of opiate modulation of intracranial self-stimulation (ICSS). Biphasic, dose-related changes in ICSS responding are described following IP administration of morphine sulfate (1-25 mg/kg) and levorphanol tartrate (LEV, 0.5-5 mg/kg). Similar patterns of response modification are reported following intraventricular (IVt) administration of LEV (0.01-0.2 muMoles) LEV's enantiomorph, dextrorphan, was not found to elicit comparable effects after either IP or IVt administration. Both the facilitatory and the depressant phases of LEV's action were antagonized by naltrexone (10 microgram, IVt), which had no apparent effect on ICSS by itself. Complete tolerance developed to the suppression of responding by 2.5 mg/kg LEV (IP) but not to the facilitatory effect of 0.5 mg/kg (IP), during a 5-day course of administration. The implications of these results for opiate reinforcement theory are discussed and possible mechanisms are advanced.

  2. Contribution of opiates in sudden asthma deaths.

    Science.gov (United States)

    Hlavaty, Leigh; Hansma, Patrick; Sung, LokMan

    2015-03-01

    Asthma is a common disease in the United States and is frequently encountered during medicolegal autopsies. Patients are often young and have a witnessed collapse or are found dead. Opiate abuse is also pervasive and is repeatedly seen in death investigations. All cases over a 7-year period involving asthma investigated at the Wayne County Medical Examiner's Office were reviewed for demographics, circumstances, autopsy toxicology findings, and cause and manner of death. Ninety-four cases met these criteria. Ten cases (10.5%) were positive for opiates, 8 listed drugs as the cause of death, and 2 listed asthma. Of cases with established asthma opiate positivity, 8 (80%) were found dead, and only one had a witnessed collapse. Compared with those without opiate abuse, asthmatic patients abusing opiates had a higher mean age, no reported respiratory symptoms immediately preceding death, and higher frequency of being found dead. A discernable difference exists between deaths in asthmatic patients in the presence of opiates and those without. These findings indicate that it may be possible to predict the presence of opiates given history investigation information, thereby focusing toxicology panels to promote cost-effective practices when ordering supportive tests.

  3. Quantitative EEG and Low-Resolution Electromagnetic Tomography (LORETA) Imaging of Patients Undergoing Methadone Treatment for Opiate Addiction.

    Science.gov (United States)

    Wang, Grace Y; Kydd, Robert R; Russell, Bruce R

    2016-07-01

    Methadone maintenance treatment (MMT) has been used as a treatment for opiate dependence since the mid-1960s. Evidence suggests that methadone binds to mu opiate receptors as do other opiates and induces changes in neurophysiological function. However, little is known, about how neural activity within the higher frequency gamma band (>30 Hz) while at rest changes in those stabilized on MMT despite its association with the excitation-inhibition balance within pyramidal-interneuron networks. Our study investigated differences in resting gamma power (37-41 Hz) between patients undergoing MMT for opiate dependence, illicit opiate users, and healthy controls subjects. Electroencephalographic data were recorded from 26 sites according to the international 10-20 system. Compared with the healthy controls subjects, people either undergoing MMT (mean difference [MD] = 0.32, 95% CI = 0.09-0.55, P opiates (MD = 0.31, 95% CI = 0.06-0.56, P = .01) exhibited significant increased gamma power. The sLORETA (standardized low-resolution electromagnetic tomography) between-group comparison revealed dysfunctional neuronal activity in the occipital, parietal, and frontal lobes in the patients undergoing MMT. A more severe profile of dysfunction was observed in those using illicit opiates. Our findings suggest that long-term exposure to opioids is associated with disrupted resting state network, which may be reduced after MMT.

  4. [Antihypoxic properties of opiates and substance P].

    Science.gov (United States)

    Vlasova, I G; Torshin, V I

    2001-01-01

    Using survival slices of the rat cerebellum, we studied the influence of opiates (alpha- and beta-endorphines, met-enkephalines) as well as substance P (SP) on the impulse activity (IA) of neurons. Low doses of the studied substances (10(-8)-10(-10) M) for the most part increased the IA of the neurons, while high doses (10(6)-10(-5) M) produced biphasic reaction (inhibition-excitation). It is supposed that opiates and SP act as transmitters in the cerebellum. Under increasing hypoxia, opiates and SP manifested antixypoxic properties both in low O22 concentration and under reoxygenation. Opiates and SP proved to be natural antihypoxants involved not only in nociception mechanisms but also in brain adaptation to oxygen deficiency.

  5. Differentiation of personality types among opiate addicts.

    Science.gov (United States)

    Blatt, S J; Berman, W H

    1990-01-01

    A wide range of studies indicate that although sociopathic characteristics are predominant in opiate addiction, depressive and psychotic features are also frequently observed. To test the hypothesis that there are really three types of individuals who become addicted to opiates (rather than a single, predominant personality style), fifty-three opiate addicts were given the Loevinger Sentence Completion Test, the Bellak Ego Functions Interview, and the Rorschach. Variables derived from these three procedures were submitted to cluster and discriminant function analyses. Three groups of addicts were identified--those primarily with impaired interpersonal relationships and affective lability (42%), those primarily characterized by thought disorder and impaired ego functioning (30%), and a group with diminished ideational and verbal activity (28%). Comparison of the assessment of these three groups with independently defined normal, neurotic, and schizophrenic samples provided support for three opiate-addicted personality types, each respectively characterized as character disordered, borderline psychotic, and depressed. Although there seems to be a predominance of character-disordered individuals who become addicted to opiates, the data indicate several additional types of opiate addicts with different types of psychopathology who may require different approaches to management and treatment.

  6. 'Lingering' opiate deaths? Concentration of opiates in medulla and femoral blood.

    Science.gov (United States)

    Naso-Kaspar, Claire K; Herndon, Grant W; Wyman, John F; Felo, Joseph A; Lavins, Eric S; Gilson, Thomas P

    2013-10-01

    'Lingering death' cases occur when the circumstances of death indicate an opiate overdose, but measured opiate blood levels are only in the therapeutic range; death results from cardiac and respiratory depression. This study examined the relative concentration of opiates in femoral blood and in the medulla oblongata (sites for cardiac and respiratory control) from 41 cases to determine whether a difference in opiate concentration might explain lingering deaths. Opiates from blood and medulla were analyzed using GC-EI-MS in selective ion monitoring mode. Results were correlated with gross and microscopic findings of the lungs and with cause and manner of death. Opiate concentrations for morphine, codeine and 6-acetylmorphine (6-AM) were higher in the medulla than in blood. The brain: blood ratio for the analytes demonstrated an increasing ratio from morphine, to codeine, to 6-AM (1.42, 2.48 and 4.86), which corresponds to the relative lipophilicity of these analytes. The average right and left lung weights were 762 and 668 g, respectively. Histologic examination showed edema, and/or polarizable microemboli, acute bronchopneumonia and acute bronchitis. The preferential distribution of opiates to medulla suggests that lingering opiate deaths may be explained, at least in part, because of higher relative concentrations of drug in brain, compared with femoral blood.

  7. Inhibitory effect of opiates on LPS mediated release of TNF and IL-8.

    Science.gov (United States)

    Bastami, Salumeh; Norling, Cecilia; Trinks, Cecilia; Holmlund, Birgitta; Walz, Thomas M; Ahlner, Johan; Uppugunduri, Srinivas

    2013-06-01

    Most patients with advanced cancer experience severe pain and are often treated with opiates. Cancer patients are especially susceptible to opportunistic infections due to treatment with immunosuppressive and cytostatic drugs. Since opiates have been demonstrated to have immunomodulatory effects, it is of clinical importance to evaluate potential differences between commonly used opiates with regard to their effect on the immune system. The aim of this study was to evaluate the effect of morphine, tramadol, fentanyl and ketobemidone on the functioning of the immune system with special reference to TNF and IL-8 release. Method. U-937 cells were preincubated with different concentrations of opioids followed by stimulation with LPS 100 μg/ml for three hours. The effect of opioids on the levels of cytokine mRNA was studied using RT-PCR. Erk and Akt phosphorylation was also measured by Western blot. Results. All opioids with the exception of fentanyl were capable of inhibiting TNF release from U-937 cells. Morphine had no effect on IL-8 release but the effect of other opiates was almost the same as the effect on TNF. All opioids with the exception of fentanyl were capable of inhibiting production of mRNA for TNF and IL-8. The observed effects of opiates were not always reversible by naloxone, suggesting that the effects might be mediated by other receptors or through a non-receptor mediated direct effect. Although preliminary evidence suggests the involvement of Erk and Akt pathways, further studies are needed to unravel the intracellular pathways involved in mediating the effects of opiates. Our data suggests that the order of potency with regard to inhibition of cytokine release is as follows: tramadol > ketobemidone > morphine > fentanyl. Conclusion. Further studies are needed to understand the clinical implications of the observed immunosuppressive effects of tramadol and ketobemidone and to improve opioid treatment strategies in patients with cancer.

  8. [Impact of opiates on dopaminergic neurons].

    Science.gov (United States)

    Kaufling, Jennifer; Freund-Mercier, Marie-José; Barrot, Michel

    2016-01-01

    Since the work of Johnson and North, it is known that opiates increase the activity of dopaminergic neurons by a GABA neuron-mediated desinhibition. This model should however be updated based on recent advances. Thus, the neuroanatomical location of the GABA neurons responsible for this desinhibition has been recently detailed: they belong to a brain structure in continuity with the posterior part of the ventral tegmental area and discovered this past decade. Other data also highlighted the critical role played by glutamatergic transmission in the opioid regulation of dopaminergic neuron activity. During protracted opiate withdrawal, the inhibitory/excitatory balance exerted on dopaminergic neurons is altered. These results are now leading to propose an original hypothesis for explaining the impact of protracted opiate withdrawal on mood.

  9. Opioid Antagonists May Reverse Endogenous Opiate “Dependence” in the Treatment of Self-Injurious Behavior

    Directory of Open Access Journals (Sweden)

    Curt A. Sandman

    2011-01-01

    Full Text Available Self-injurious behavior (SIB is a primary reason that individuals with neurodevelopmental disabilities (NDD are either retained in restrictive environments or are administered psychotropic medication. There are no known causes and no universally accepted treatments for this complex behavior among individuals with NDD. There is developing evidence, however, that individuals exhibiting SIB have a disturbance of the opiate-mediated pain and pleasure system. One hypothesis is that SIB reflects insensitivity to pain and general sensory depression (hypoalgesia, perhaps related to chronic elevation of endogenous opiates. For instance, many self-injurious individuals do not exhibit the usual signs of pain after their “injurious” behavior. Moreover, for some individuals the addictive properties of elevated endogenous opiates (euphoria may be responsible for maintaining their SIB. In this perspective, SIB may be viewed as an addiction because it supplies the "fix" for tolerant, down-regulated opiate receptors. Reports that levels of endogenous opiates at rest and after SIB episodes predict positive responses to opiate blockers (e.g., naltrexone provide further support for opiate-mediated SIB and form the basis for a rational treatment strategy. Although the long term effects of opiate blockers on SIB are unknown, reduction in SIB following acute treatment provides support that a specific biological system may be dysregulated in a subgroup of patients. It is concluded that naltrexone produces a clinically significant reduction in the serious and life-threatening behavior of self injury for individuals who have not been responsive to any other type of treatment. Several suggestions and cautions are provided for regimens of naltrexone treatment of SIB.

  10. Reciprocal Evolution of Opiate Science from Medical and Cultural Perspectives.

    Science.gov (United States)

    Stefano, George B; Pilonis, Nastazja; Ptacek, Radek; Kream, Richard M

    2017-06-13

    Over the course of human history, it has been common to use plants for medicinal purposes, such as for providing relief from particular maladies and self-medication. Opium represents one longstanding remedy that has been used to address a range of medical conditions, alleviating discomfort often in ways that have proven pleasurable. Opium is a combination of compounds obtained from the mature fruit of opium poppy, papaver somniferum. Morphine and its biosynthetic precursors thebaine and codeine constitute the main bioactive opiate alkaloids contained in opium. Opium usage in ancient cultures is well documented, as is its major extract morphine. The presence of endogenous opiate alkaloids and opioid peptides in animals owe their discovery to their consistent actions at particular concentrations via stereo select receptors. In vitro expression of morphine within a microbiological industrial setting underscores the role it plays as a multi-purpose pharmacological agent, as well as reinforcing why it can also lead to long-term social dependence. Furthermore, it clearly establishes a reciprocal effect of human intelligence on modifying evolutionary processes in papaver somniferum and related plant species.

  11. Attributions and Relapse in Opiate Addicts.

    Science.gov (United States)

    Bradley, Brendan P.; And Others

    1992-01-01

    Investigated whether attributions of opiate addicts would predict abstinence and reactions to abstinence violations. Found that addicts who at admission attributed to themselves greater responsibility for negative outcomes and who attributed relapse episodes to more personally controllable factors were subsequently more likely either to be…

  12. Opiates and elderly: Use and side effects

    Directory of Open Access Journals (Sweden)

    Diane L Chau

    2008-06-01

    Full Text Available Diane L Chau1, Vanessa Walker2, Latha Pai3, Lwin M Cho4University of Nevada School of Medicine, Reno, NV, USA 1Division Geriatric Medicine, 2Internal Medicine, 3Psychiatry, 4Geriatric Medicine, Sierra Nevada Healthcare System, Veterans Affairs Medical Center, Reno, NV, USAAbstract: The evaluation of pain and the subsequent issue of pain control is a clinical challenge that all healthcare providers face. Pain in the elderly population is especially difficult given the myriad of physiological, pharmacological, and psychological aspects of caring for the geriatric patient. Opiates are the mainstay of pain treatment throughout all age groups but special attention must be paid to the efficacy and side effects of these powerful drugs when prescribing to a population with impaired metabolism, excretion and physical reserve. In a random chart review of 300 US veterans, 44% of those receiving an analgesic also received opioids. The increasing use of opiates for pain management by healthcare practitioners requires that those prescribing opioids be aware of the special considerations for treating the elderly. This article will address the precautions one must take when using opiates in the geriatric population, as well as the side effects and ways to minimize them.Keywords: opiates, pain, elderly, side effects

  13. Behavioral measures of anxiety during opiate withdrawal.

    Science.gov (United States)

    Grasing, K; Wang, A; Schlussman, S

    1996-10-01

    Heightened anxiety is a major component of the withdrawal syndromes associated with ethanol and sedative hypnotic medications. Because of similarities between the opiate and sedative-hypnotic withdrawal syndromes as well as data implicating heightened noradrenergic tone with opiate withdrawal, we investigated changes in anxiety measures identified by plus-maze and social interaction testing during opiate withdrawal. Because Sprague Dawley rats had very low levels of entry into plus-maze open arms, further studies were conducted using the Long-Evans strain. Long-Evans rats received continuous infusions of morphine sulfate at 44 mg/kg per day delivered by osmotic pump over 7 days while control animals received inert implants. During the first 3 days of withdrawal, the number and time of entries into open and closed arms of a plus-maze was recorded. Both social and aggressive behaviors were scored durings pairings of groups of two socially naive animals. Body weight was significantly reduced in morphine-treated animals prior to and during withdrawal. Both the number of entries into open plus-maze arms and the time spent in open areas increased over the 3 days of testing. However, no difference in plus-maze activity was detected between morphine-treated and control subjects. On the third day of withdrawal, social interaction time was greater in pairs of withdrawn and control subjects compared to pairs of two control subjects. In conclusion, behavioral measures of anxiety are not increased during opiate withdrawal.

  14. Drug Craving Terminology among Opiate Dependents

    Directory of Open Access Journals (Sweden)

    Masoomeh Maarefvand

    2013-06-01

    Full Text Available Objective:Drug craving is defined as an urge to continue substance abuse. Drug dependents use different terms to express their subjective feeling of craving. This study was an attempt to generate an understanding of craving terminology among different groups of Persian speaking Iranian opiate dependents.Method:Terms used for the meaning of drug craving were listed by 36 ex-opiate dependents in focus group discussion meetings in the first phase of the study. These terms were composed from Craving Terms Questionnaire. In the second phase, 120 subjects in 3 groups of opiate dependents and a group of Current Opiate Abusers rated usage frequency of each term in the questionnaire under a Twelve-Step Program, Methadone Maintenance, and Other Abstinence-based Programs.Results:Eighty nine terms were categorized in stimulation and triggering, attention bias and obsession, decision making difficulty, information processing impairment, withdrawal induction, drug euphoric experience, mental urge, motor control problem, negative valancing and stigmatizing. Terms for the three categories of mental urge, attention bias and obsession and motor control problem were used more than others. Patients in Methadone Maintenance Treatment (MMT group used different categories of craving terms in comparison to other groups. Abstinent cases reported higher total score for craving terms in comparison to other groups in Twelve-Step Program and other abstinence-based programs.Conclusion:Each craving-related term is associated with some aspects of the multidimensional concept of craving. A drug-craving thesaurus could provide a better understanding of craving nature from a drug dependent point of view. There are differences among abstinence vs. maintenance based treated opiate dependents in using craving terms. Addiction therapists will benefit from accessing drug dependents’ lexicon to assess and create therapeutic alliance with their clients.

  15. 阻断阿片受体可改变吗啡成瘾大鼠下边缘皮质脑电功率谱成分%Antagonism of opiate receptor by naloxone could change the infralimbic cortical EEG power spectrum components in morphine addicted rats

    Institute of Scientific and Technical Information of China (English)

    和晓明; 王晓琴; 王功伍

    2015-01-01

    旨在探讨纳洛酮阻断阿片受体后吗啡成瘾大鼠前额叶下边缘皮质脑电功率谱的变化。成年雄性Wistar大鼠接受每48 h固定剂量吗啡(10 mg/kg)或生理盐水交替注射连续8 d,经戒断实验和条件性位置偏爱( conditioned place preference, CPP)实验确认建立吗啡成瘾模型;然后记录CPP大鼠麻醉状态前额叶下边缘皮质EEG,分析注射阿片受体拮抗剂纳洛酮前后的EEG功率谱成分。结果发现纳洛酮可使吗啡成瘾大鼠EEG功率谱theta频段功率(P <0.01)和占总功率的比例(P <0.05)显著升高,gamma频段功率也显著升高(P <0.05)。结果表明纳洛酮阻断阿片受体可改变吗啡成瘾大鼠前额叶下边缘皮质EEG功率谱成分。%The purpose of present study is to investigate the effect of antagonism of opiate receptor by naloxone on the prefrontal infral-imbic cortical EEG power in morphine addicted rat.Forty adult male Wistar rats were treated with morphine (10 mg/kg, sc.) every 48 h for consecutive 8 d to establish addicted rat model.The model had been confirmed by withdrawal test and conditioned place prefer-ence ( CPP) test.Then the EEG signals were recorded from the infralimbic cortex ( ILC) ( one subarea of the prefrontal cortex) in an-esthetized CPP rats.Results showed that 30 min after naloxone injection, the EEG powers of theta band (4-7 Hz) and 2 gamma bands (30-49 Hz and 51-100 Hz) and the percentage of theta band in morphine rats increased significantly (All P <0.05).In conclusion, present study indicated that antagonism of opiate receptor by naloxone could enhance the ILC EEG power of theta band and gamma band in morphine addicted rats, and the EEG power changing would be an electrophysiological index of ILC cognitive function and ad-dictive behaviors.

  16. Endogenous Opiates and Behavior: 2006

    OpenAIRE

    Bodnar, Richard J.

    2007-01-01

    This paper is the twenty-ninth consecutive installment of the annual review of research concerning the endogenous opioid system, now spanning thirty years of research. It summarizes papers published during 2006 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localiz...

  17. Positron-emissionstomografisk kortlaegning af den levende menneskehjernes receptorer

    DEFF Research Database (Denmark)

    Gjedde, A

    2001-01-01

    tracers are used in diseases of the basal ganglia, whereas serotonin, benzodiazepine, and opiate tracers are used in lesions of the cerebral cortex. PET has revealed loss of dopaminergic terminals and dopamine synthetic capacity in Parkinson's disease, MPTP intoxication, and Lesch-Nyhan's syndrome...... receptors in Alzheimer's disease, and benzodiazepine and opiate receptors in stroke, epilepsy, and Huntington's chorea; altered opiate receptors in chronic pain and drug abuse; and release of opiates in analgesia; but changes in serotonin synthesis, transport, and binding in affective or psychotic disorders...

  18. Leg edema from intrathecal opiate infusions.

    Science.gov (United States)

    Aldrete, J A; Couto da Silva JM

    2000-01-01

    Despite the increasing popularity of intrathecal infusions to treat patients with long-term non-cancer-related pain, this therapy is not without serious side-effects. Five out of 23 patients who had intrathecal infusions of opiates for longer than 24 months developed leg and feet edema. As predisposing factors, cardiovascular disease, deep venous thrombosis, peripheral vascular disease, and venous stasis of the lower extremities were considered. Every patient who developed pedal and leg edema after the implantation of an infusion pump was also found to have leg edema and venous stasis prior to the time when the pump was inserted. This complication was severe enough to limit their physical activity, and to produce lymphedema, ulcerations and hyperpigmentation of the skin. Reduction of the edema occurred when the dose of the opiate was decreased, and in two cases in which the infusion was discontinued, there was almost complete resolution of the syndrome. It appears that the pre-existence of pedal edema and of venous stasis is a relative contraindication to the long-term intrathecal infusion of opiates in patients with chronic non-cancer pain. Copyright 2000 European Federation of Chapters of the International Association for the Study of Pain.

  19. Opiate withdrawal complicated by tetany and cardiac arrest.

    Science.gov (United States)

    Kugasia, Irfanali R; Shabarek, Nehad

    2014-01-01

    Patients with symptoms of opiate withdrawal, after the administration of opiate antagonist by paramedics, are a common presentation in the emergency department of hospitals. Though most of opiate withdrawal symptoms are benign, rarely they can become life threatening. This case highlights how a benign opiate withdrawal symptom of hyperventilation led to severe respiratory alkalosis that degenerated into tetany and cardiac arrest. Though this patient was successfully resuscitated, it is imperative that severe withdrawal symptoms are timely identified and immediate steps are taken to prevent catastrophes. An easier way to reverse the severe opiate withdrawal symptom would be with either low dose methadone or partial opiate agonists like buprenorphine. However, if severe acid-base disorder is identified, it would be safer to electively intubate these patients for better control of their respiratory and acid-base status.

  20. Opiate Withdrawal Complicated by Tetany and Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Irfanali R. Kugasia

    2014-01-01

    Full Text Available Patients with symptoms of opiate withdrawal, after the administration of opiate antagonist by paramedics, are a common presentation in the emergency department of hospitals. Though most of opiate withdrawal symptoms are benign, rarely they can become life threatening. This case highlights how a benign opiate withdrawal symptom of hyperventilation led to severe respiratory alkalosis that degenerated into tetany and cardiac arrest. Though this patient was successfully resuscitated, it is imperative that severe withdrawal symptoms are timely identified and immediate steps are taken to prevent catastrophes. An easier way to reverse the severe opiate withdrawal symptom would be with either low dose methadone or partial opiate agonists like buprenorphine. However, if severe acid-base disorder is identified, it would be safer to electively intubate these patients for better control of their respiratory and acid-base status.

  1. Impact of opiate addiction on neuroinflammation in HIV.

    Science.gov (United States)

    Byrd, Desiree; Murray, Jacinta; Safdieh, Gabriella; Morgello, Susan

    2012-10-01

    To investigate the independent and interactive effects of opiate addiction and HIV on neuroinflammation, we measured microglial/macrophage activation and astrogliosis in multiple regions of human brain. Samples of thalamus, frontal gray matter, and frontal white matter were obtained from 46 individuals categorized as: HIV negatives, HIV-negative opiate addicts, HIV positives, HIV-positive opiate addicts, HIV encephalitis (HIVE), and HIVE opiate addicts. Activated brain microglia/macrophages and astrocytosis were quantified by morphometric analysis of immunohistochemical stains for CD68, HLA-D, CD163, and GFAP. The effects of HIV grouping, opiate addiction, and their interaction on expression of the markers were examined in a series of two-way ANOVAs. In opiate addicts, there was generally higher baseline expression of CD68 and HLA-D in HIV negatives, and lower expression in HIV and HIVE, compared to individuals without opiate abuse. Thus, for these markers, and for GFAP in frontal gray, opiates were associated with attenuated HIV effect. In contrast, for CD163, opiates did not significantly alter responses to HIV, and HIV effects were variably absent in individuals without opiate abuse. The divergent impact that opiate addiction displays on these markers may suggest a generally immunosuppressive role in the CNS, with decreased HIV-associated activation of markers CD68 and HLA-D that potentially reflect neurotoxic pathways, and preservation of CD163, thought to be an indicator of neuroprotective scavenger systems. These results suggest a complex impact of opiates on neuroinflammation in baseline and virally stimulated states.

  2. Tianeptine prevents respiratory depression without affecting analgesic effect of opiates in conscious rats.

    Science.gov (United States)

    Cavalla, David; Chianelli, Fabio; Korsak, Alla; Hosford, Patrick S; Gourine, Alexander V; Marina, Nephtali

    2015-08-15

    Respiratory depression remains an important clinical problem that limits the use of opiate analgesia. Activation of AMPA glutamate receptors has been shown to reverse fentanyl-induced respiratory changes. Here, we explored whether tianeptine, a drug known for its ability to phosphorylate AMPA receptors, can be used to prevent opiate-induced respiratory depression. A model of respiratory depression in conscious rats was produced by administration of morphine (10mg/kg, i.p.). Rats were pre-treated with test compounds or control solutions 5min prior to administration of morphine. Respiratory activity was measured using whole-body plethysmography. In conscious animals, tianeptine (2 and 10mg/kg, ip) and DP-201 (2-(4-((3-chloro-6-methyl-5,5-dioxido-6,11-dihydrodibenzo[c,f][1,2] thiazepin-11-yl)amino)butoxy)acetic acid; tianeptine analogue; 2mg/kg, ip) triggered significant (~30%) increases in baseline respiratory activity and prevented morphine-induced respiratory depression. These effects were similar to those produced by an ampakine CX-546 (15mg/kg, ip). The antinociceptive effect of morphine (hot plate test) was unaffected by tianeptine pre-treatment. In conclusion, the results of the experiments conducted in conscious rats demonstrate that systemic administration of tianeptine increases respiratory output and prevents morphine-induced respiratory depression without interfering with the antinociceptive effect of opiates.

  3. Opiate addicts in and outside of treatment; Different populations?

    NARCIS (Netherlands)

    M.A. Goossensen (Anne)

    1997-01-01

    textabstractThe core of this study is related to the insight that the population of opiate addicls is quite an invisible group. Some paris of this group can be identified at treatment institutions and in prisons. However, a large pari of the opiate addicls is hard to detect. This is because

  4. Neurocognitive impairments at various stages of clinical opiate addiction

    Directory of Open Access Journals (Sweden)

    Faniya Shigakova

    2012-05-01

    Full Text Available In opiate addicts with various duration of drug use neurocognitive impairments as well as a number of typical physical changes occurring in the brain were registered. The opiate addicts’ cerebral hemodynamics and higher brain functions were examined by drug use duration and patient’s age.

  5. Opiates May Have Neuroprotective Properties against Neurodegeneration and Premature Death

    OpenAIRE

    Alen J Salerian

    2015-01-01

    Endorphins and endorphin agonists play a crucial role in the neuromodulation of mood, anxiety, pain and addiction. Review of clinical studies seem to elucidate possible protective role of opiates against neurodegeneration and premature death. The historical, biological, experimental, clinical and neuroimaging data strongly support the potential properties of opiates as neuro protectors.

  6. Opiate addicts in and outside of treatment; Different populations?

    NARCIS (Netherlands)

    M.A. Goossensen (Anne)

    1997-01-01

    textabstractThe core of this study is related to the insight that the population of opiate addicls is quite an invisible group. Some paris of this group can be identified at treatment institutions and in prisons. However, a large pari of the opiate addicls is hard to detect. This is because their il

  7. Opiate-induced respiratory depression in young pediatric burn patients.

    Science.gov (United States)

    Gibbons, J; Honari, S R; Sharar, S R; Patterson, D R; Dimick, P L; Heimbach, D M

    1998-01-01

    Three children younger than 5 with minor burns (< 5% total body surface area) experienced opiate-induced respiratory depression early in hospitalization. This prompted a decrease in the recommended opiate analgesic-dose ranges on our pediatric worksheet. In reviewing 57 admissions, 31 pre- and 26 post-dose change, the amount of opioid equivalents/kg received on admission day did not differ significantly. However, the incidence of respiratory depressive events decreased. Lower opiate-dose guidelines might improve the safe administration of these medications to young children. Other factors- such as concomitant sedative medications, previously administered opiate analgesics, and underlying medical conditions-also must be considered when giving initial doses of opiate analgesics in the burn center.

  8. Burden and nutritional deficiencies in opiate addiction- systematic review article.

    Science.gov (United States)

    Nabipour, Sepideh; Ayu Said, Mas; Hussain Habil, Mohd

    2014-08-01

    Addiction to the illicit and prescribed use of opiate is an alarming public health issue. Studies on addictive disorders have demonstrated severe nutritional deficiencies in opiate abusers with behavioral, physiological and cognitive symptoms. Opiate addiction is also link with a significant number of diseases including Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV) and other blood borne diseases generally stem from the use of needles to inject heroin. The use of medication assisted treatment for opioid addicts in combination with behavioural therapies has been considered as a highly effective treatment. Methadone is a long-lasting μ-opioid agonist and a pharmacological tool which attenuates withdrawal symptoms effectively replacement therapies. This review article aims to explain opiate addiction mechanisms, epidemiology and disease burden with emphasis on dietary and nutritional status of opiate dependent patients in methadone maintenance therapy.

  9. Burden and nutritional deficiencies in opiate addiction- systematic review article.

    Directory of Open Access Journals (Sweden)

    Sepideh Nabipour

    2014-08-01

    Full Text Available Addiction to the illicit and prescribed use of opiate is an alarming public health issue. Studies on addictive disorders have demonstrated severe nutritional deficiencies in opiate abusers with behavioral, physiological and cognitive symptoms. Opiate addiction is also link with a significant number of diseases including Human Immunodeficiency Virus (HIV, Hepatitis C Virus (HCV and other blood borne diseases generally stem from the use of needles to inject heroin. The use of medication assisted treatment for opioid addicts in combination with behavioural therapies has been considered as a highly effective treatment. Methadone is a long-lasting μ-opioid agonist and a pharmacological tool which attenuates withdrawal symptoms effectively replacement therapies. This review article aims to explain opiate addiction mechanisms, epidemiology and disease burden with emphasis on dietary and nutritional status of opiate dependent patients in methadone maintenance therapy.

  10. [{sup 11}C]-methyl 4-[(3,4-dichlorophenyl)acetyl]-3-[(1-pyrrolidinyl)methyl] -1-piperazinecarboxylate ([{sup 11}C]GR89696): synthesis and in vivo binding to kappa opiate receptors

    Energy Technology Data Exchange (ETDEWEB)

    Ravert, Hayden T.; Mathews, William B.; Musachio, John L.; Scheffel, Ursula; Finley, Paige; Dannals, Robert F

    1999-10-01

    GR89696, racemic methyl 4-[(3,4-dichlorophenyl)acetyl]-3-[(1-pyrrolidinyl) methyl] -1-piperazinecarboxylate, a kappa opioid receptor ligand, was labeled with [{sup 11}C]methyl chloroformate. The radiochemical yield was 20% with an observed specific radioactivity of 75.5 GBq/{mu}mol at end of synthesis (2,040 mCi/{mu}mol). Five minutes after intravenous administration, 5.4% of the injected dose accumulated in mouse whole brain. Brain region to cerebellar ratios increased over time with ratios at 90 min of 7.8, 5.6, and 4.5 for the hypothalamus, olfactory tubercle, and striatum, respectively. The uptake of [{sup 11}C]GR89696 correlated with known kappa opioid receptor densities and was inhibited by kappa opioid selective drugs.

  11. Impaired periamygdaloid-cortex prodynorphin is characteristic of opiate addiction and depression.

    Science.gov (United States)

    Anderson, Sarah Ann R; Michaelides, Michael; Zarnegar, Parisa; Ren, Yanhua; Fagergren, Pernilla; Thanos, Panayotis K; Wang, Gene-Jack; Bannon, Michael; Neumaier, John F; Keller, Eva; Volkow, Nora D; Hurd, Yasmin L

    2013-12-01

    Negative affect is critical for conferring vulnerability to opiate addiction as reflected by the high comorbidity of opiate abuse with major depressive disorder (MDD). Rodent models implicate amygdala prodynorphin (Pdyn) as a mediator of negative affect; however, evidence of PDYN involvement in human negative affect is limited. Here, we found reduced PDYN mRNA expression in the postmortem human amygdala nucleus of the periamygdaloid cortex (PAC) in both heroin abusers and MDD subjects. Similar to humans, rats that chronically self-administered heroin had reduced Pdyn mRNA expression in the PAC at a time point associated with a negative affective state. Using the in vivo functional imaging technology DREAMM (DREADD-assisted metabolic mapping, where DREADD indicates designer receptors exclusively activated by designer drugs), we found that selective inhibition of Pdyn-expressing neurons in the rat PAC increased metabolic activity in the extended amygdala, which is a key substrate of the extrahypothalamic brain stress system. In parallel, PAC-specific Pdyn inhibition provoked negative affect-related physiological and behavioral changes. Altogether, our translational study supports a functional role for impaired Pdyn in the PAC in opiate abuse through activation of the stress and negative affect neurocircuitry implicated in addiction vulnerability.

  12. The enhancement of astrocytic-derived monocyte chemoattractant protein-1 induced by the interaction of opiate and HIV tat in HIV-associated dementia

    Institute of Scientific and Technical Information of China (English)

    Xiao Han

    2009-01-01

    HIV-assodated dementia (HAD) is a public health problem and is particularly prevalent in drug abusers. The neuropathogenesis of human immunodeficiency virus (HIV) infection involves a complex cascade of inflammatory events, including monocyte/macrophage infiltration in the brain, glial immune activation and release of neurotoxic substances. In these events, astrocytic-derived monocyte chemoattractant protein-1 (MCP-1) plays an important role, whose release is elevated by HIV transactivator of transcription (HIV tat) and could be further elevated by opiates. This review will also consider some critical factors and events in MCP-1 enhancement induced by the interactions of opiate and HIV tat, including the mediating role of mu opioid receptor (MOR) and CCR2 as well as the possible signal transduction pathways within the cells. Finally, it will make some future perspectives on the exact pathways, new receptors and target cells, and the vulnerability to neurodegeneration with HIV and opiates.

  13. Is the cutaneous silent period an opiate-sensitive nociceptive reflex?

    Science.gov (United States)

    Inghilleri, Maurizio; Conte, Antonella; Frasca, Vittorio; Berardelli, Alfredo; Manfredi, Mario; Cruccu, Giorgio

    2002-05-01

    In humans, high-intensity electrical stimuli delivered to the fingers induce an inhibitory effect on C7-T1 motoneurons. This inhibitory reflex, called the cutaneous silent period (CSP) is considered a defense response specific for the human upper limbs. It is not clear whether the CSP-like other defense responses such as the corneal reflex and the R III reflex-is an opiate-sensitive nociceptive reflex. Because opiates suppress some, but not all, nociceptive reflexes, we studied the effect of the narcotic-analgesic drug fentanyl on the CSP and the R III reflex. The CSP was recorded from the first dorsal interosseous (FDI) muscle in seven normal subjects during voluntary contraction, before and 10 and 20 min after fentanyl injection. To assess possible fentanyl-induced changes, we also tested the effect of finger stimulation on motor evoked potentials (MEPs) elicited in the FDI muscle by transcranial magnetic stimulation before and after fentanyl injection. Fentanyl-induced changes were also studied on the R III reflex recorded from the biceps femoris muscle. Fentanyl, as expected, suppressed the R III reflex but failed to change the inhibitory effect of finger stimulation on FDI motoneurons. Finger stimulation reduced the size of MEPs in the FDI, and fentanyl injection left this inhibitory effect unchanged. The differential fentanyl-induced modulation of the CSP and R III reflex provides evidence that the CSP circuit is devoid of mu-opiate receptors and is therefore an opiate-insensitive nociceptive reflex, which may be useful in the assessment of central-acting, non-opioid drugs.

  14. [NON-ONCOLOGIC CHRONIC PAIN TREATMENT WITH OPIATES].

    Science.gov (United States)

    Molas Ferrer, Glòria; Castellà Kastner, Montse; Lombraña Mencia, María

    2014-09-01

    Non-oncologic chronic pain is a very common symptom. It causes great impact on daily activities of people who suffer it. The incidence of this type of pain is rising due to the increase in life expectancy. The most affected population is geriatric population. Back pain, osteoarthritic pain and neuropathic pain are the most prevalent types of non-oncologic chronic pain. Opiates, among other analgesic drugs, are used to alleviate this type of pain. Opiates are divided into minor opiates (tramadol, codeine) and major opiates (morphine, fentanyl, oxycodone, methadone). Opiates are very effective to treat pain, but they also have important adverse effects that we must know and try to prevent. One of these adverse effects is the opiates ability to cause dependence, tolerance, addiction and other aberrant behaviors. Terminology of these concepts is sometimes confusing. It is necessary to be careful and control the patient periodically in order to avoid these aberrant behaviors. However, if health professionals take precautions to prevent these behaviors, the risk is considerably reduced. Controlling patients on opiate treatment is essential to achieve a correct use if these drugs.

  15. Variable angle of strabismus related to timing of opiate ingestion.

    Science.gov (United States)

    Ross, Jonathan J; Brown, Valerie; Fern, Alasdair I

    2009-04-01

    Heroin (diamorphine) is a highly addictive opiate with potential for misuse. A small number of reports have linked the commencement of heroin misuse to acute exotropia with diplopia and subsequent withdrawal to esotropia in individuals without previous symptoms.(1-5) We describe a young adult who sought strabismus surgery to correct a large-angle exotropia. Detailed patient history and orthoptic measurements at different times of the day revealed a fluctuating angle of divergence relating to the timing of opiate ingestion, rendering surgery inappropriate. We suggest that opiate misuse, which may not willingly be disclosed by patients, should be specifically asked about before acquired-strabismus surgery is undertaken in adults.

  16. Opiate reinforcement processes: re-assembling multiple mechanisms.

    Science.gov (United States)

    Bozarth, M A

    1994-11-01

    Opiate reinforcement processes can be described within the context of operant conditioning theory. Both positive and negative reinforcing effects may motivate drug-taking behavior, although the strongest evidence attributes drug-taking to a simple positive reinforcement process. Empirical research has focused largely on a positive reinforcement mechanism involving the ventral tegmental dopamine system, but three additional reinforcement mechanisms can be argued on logical grounds. These other mechanisms involve neuroadaptive changes produced by chronic opiate administration and may contribute to the strong motivational impact of opiates following long-term drug use.

  17. Clinical Manifestations of the Opiate Withdrawal Syndrome

    Directory of Open Access Journals (Sweden)

    Faniya Shigakova

    2015-09-01

    Full Text Available Currently, substance abuse is one of the most serious problems facing our society. The aim of this study was to investigate the clinical manifestations of the opiate withdrawal syndrome (OWS. The study included 112 patients (57 women and 55 men aged from 18 to 64 years with opium addiction according to the DSM-IV. To study the clinical manifestation of OWS, the special 25-score scale with four sections to assess severity of sleep disorders, pain syndrome, autonomic disorders, and affective symptoms was used. Given the diversity of the OWS symptoms, attention was focused on three clinical variants, affective, algic and mixed. The OWS affective variant was registered more frequently in women, while the mixed type of OWS was more typical of men.

  18. HIV, opiates, and enteric neuron dysfunction.

    Science.gov (United States)

    Galligan, J J

    2015-04-01

    Human immune deficient virus (HIV) is an immunosuppressive virus that targets CD4(+) T-lymphocytes. HIV infections cause increased susceptibility to opportunistic infections and cancer. HIV infection can also alter central nervous system (CNS) function causing cognitive impairment. HIV does not infect neurons but it does infect astrocytes and microglia in the CNS. HIV can also infect enteric glia initiating an intestinal inflammatory response which causes enteric neural injury and gut dysfunction. Part of the inflammatory response is HIV induced production of proteins including, Transactivator of transcription (Tat) which contribute to neuronal injury after release from HIV infected glial cells. A risk factor for HIV infection is intravenous drug use with contaminated needles and chronic opiate use can exacerbate neural injury in the nervous system. While most research focuses on the actions of Tat and other HIV related proteins and opiates on the brain, recent data indicate that Tat can cause intestinal inflammation and disruption of enteric neuron function, including alteration of Na(+) channel activity and action potential generation. A paper published in this issue of Neurogastroenterology and Motility extends these findings by identifying an interaction between Tat and morphine on enteric neuron Na(+) channels and on intestinal motility in vivo using a Tat expressing transgenic mouse model. These new data show that Tat protein can enhance the inhibitory actions of morphine on action potential generation and propulsive motility. These findings are important to our understanding of how HIV causes diarrhea in infected patients and for the use of opioid drugs to treat HIV-induced diarrhea.

  19. Illicit Use of Prescription Opiates among Graduate Students.

    Science.gov (United States)

    Varga, Matthew D; Parrish, Mark

    2015-01-01

    Through this study the authors assessed the prevalence rate, reasons for use, and poly-substance use of prescription opiates among graduate students. The authors employed a cross-sectional survey research design using an online, self-administered questionnaire to assess the prevalence rates of prescription opiate use among graduate students (N = 1,033), reasons for use, and their likelihood for poly-substance use. The survey was e-mailed to 5,000 graduate students. Graduate students (19.7%) reported illicit use of prescription opiates in their lifetime and 6.6% reported past-year illicit use. Those who indicated illicitly using prescription opiates did so for self-medication reasons; a few respondents indicated recreational use. Students using prescription opiates were 75% less likely to use marijuana; 79% less likely to use cocaine; and 75% less likely to use ecstasy. Graduate students are illicitly using prescription opiates, but primarily for self-medication, and, while doing so, are less likely to use other substances.

  20. Character pathology and neuropsychological test performance in remitted opiate dependence

    Directory of Open Access Journals (Sweden)

    Steinfeld Matthew

    2008-11-01

    Full Text Available Abstract Background Cognitive deficits and personality pathology are prevalent in opiate dependence, even during periods of remission, and likely contribute to relapse. Understanding the relationship between the two in vulnerable, opiate-addicted patients may contribute to the design of better treatment and relapse prevention strategies. Methods The Millon Multiaxial Clinical Inventory (MCMI and a series of neuropsychological tests were administered to three subject groups: 29 subjects receiving methadone maintenance treatment (MM, 27 subjects in protracted abstinence from methadone maintenance treatment (PA, and 29 healthy non-dependent comparison subjects. Relationships between MCMI scores, neuropsychological test results, and measures of substance use and treatment were examined using bivariate correlation and regression analysis. Results MCMI scores were greater in subjects with a history of opiate dependence than in comparison subjects. A significant negative correlation between MCMI scores and neuropsychological test performance was identified in all subjects. MCMI scores were stronger predictors of neuropsychological test performance than measures of drug use. Conclusion Formerly methadone-treated opiate dependent individuals in protracted opiate abstinence demonstrate a strong relationship between personality pathology and cognitive deficits. The cause of these deficits is unclear and most likely multi-factorial. This finding may be important in understanding and interpreting neuropsychological testing deficiencies in opiate-dependent subjects.

  1. Differences in depression severity and frequency of relapses in opiate addicts treated with methadone or opiate blocker after detoxification

    Directory of Open Access Journals (Sweden)

    Jovanović Tatjana

    2012-01-01

    Full Text Available Background/Aim. Relapse of opiate dependence is a common occurrence after detoxification and introduction of opiate addicts in abstinence from opiates. Clinical evaluation showed that over 90% of opiate addicts exhibit depressive manifestations during detoxification, or develop post-detoxification depression. The aim of this study was to determine differences in the frequency of relapses, severity and course of depression during a of 6-month period, and previous patterns of use of opioids in the two groups of opiate addicts treated by two different therapeutic modalities. Methods. The results of the two groups of opiate addicts were compared: the patients on substitution methadone treatment (M and the patients treated with opiate blocker naltrexone (B. In all the patients, clinical and instrumental evaluations confirmed depressive syndrome. Opioid relapses were diagnosed by the panel test for rapid detection of metabolites of opiates in urine. Then they were brought in connection with scores of depression and addiction variables. The Hamilton Depression Scale (HAMD and Zunge Depression Scale were the applied instruments for measuring the level of depression. All the subjects completed a questionnaire Pompidou (short version. Psychological measurements were carried out during a 6-month follow-up on three occasions. The presence of opiate metabolites in urine was controlled every two weeks. Results. Both groups of patients (M and B had high scores on HAMD during the study. The group on methadone had a strong depression in all three measurements. There was a drop in the level of depression in both experimental groups over time, which was accompanied by a decrease in the incidence of recurrence. In both tested groups the frequency of relapses was positively correlated with earlier addiction variables - intravenous application of opioids, the experience of overdose, the absence of immunization against hepatitis C and hepatitis C virus carriers

  2. Enhanced bioavailability of opiates after intratracheal administration

    Energy Technology Data Exchange (ETDEWEB)

    Findlay, J.W.A.; Jones, E.C.; McNulty, M.J.

    1986-03-01

    Several opiate analgesics have low oral bioavailabilities in the dog because of presystemic metabolism. Intratracheal administration may circumvent this first-pass effect. Three anesthetized beagles received 5-mg/kg doses of codeine phosphate intratracheally (i.t.), orally (p.o.) and intravenously (i.v.) in a crossover study. The following drugs were also studied in similar experiments: ethylmorphine hydrochloride (5 mg/kg), pholcodine bitartrate (10 mg/kg, hydrocodone bitartrate (4 mg/kg) and morphine sulfate (2.5 mg/kg). Plasma drug concentrations over the 24- to 48-hr periods after drug administrations were determined by radioimmunoassays. I.t. bioavailabilities (codeine (84%), ethylmorphine (100%), and morphine (87%)) of drugs with poor oral availabilities were all markedly higher than the corresponding oral values (14, 26, and 23%, respectively). I.t. bioavailabilities of pholcodine (93%) and hydrocodone (92%), which have good oral availabilities (74 and 79%, respectively), were also enhanced. In all cases, peak plasma concentrations occurred more rapidly after i.t. (0.08-0.17 hr) than after oral (0.5-2 hr) dosing and i.t. disposition often resembled i.v. kinetics. I.t. administration may be a valuable alternative dosing route, providing rapid onset of pharmacological activity for potent drugs with poor oral bioavailability.

  3. Opiate addiction in Republic of Srpska: Characteristics and etiology

    Directory of Open Access Journals (Sweden)

    Niškanović Jelena

    2013-01-01

    Full Text Available Opiate addiction is a significant social and health problem with a negative impact on individuals' health and their social environment. The aim of this paper is to analyze the characteristics of opiate addicts in order to determine the social and contextual factors underlying the development of addiction. All health care facilities and therapeutic communities which provide care and help addicts are required to fill in the Form of treated addicts. The analysis included people who sought treatment during the period from 25th November 2010 to 21st May 2013 in health care facilities and associations for substance abuse treatment in the Republic of Srpska. The majority of treated addicts belong to opiate addiction (N= 241: 91%. Opiate addicts are mostly males (88.8%, while 11.2% of treated opiate addicts are female. The highest percentage of opiate addicts live in urban areas (86.7%, have secondary education (73.4%, 63.3% are unemployed, while 70.5% live with primary family. Predominant etiologic factor for the development of addiction is peer or partner pressure (29%, pathology of the family as family breakdown or alcoholism (19.3%, while on the third place is low self control (16.8%. For 19.1% of opiate addicts, delinquent behavior started before taking any drugs. The presented data confirms the importance of social environment, like low family control and presence of family pathology. The mentioned factors in combination with negative peer pressure can lead to risky behavior and potential addiction.

  4. Opiate-induced suppression of rat hypoglossal motoneuron activity and its reversal by ampakine therapy.

    Directory of Open Access Journals (Sweden)

    Amanda R Lorier

    Full Text Available BACKGROUND: Hypoglossal (XII motoneurons innervate tongue muscles and are vital for maintaining upper-airway patency during inspiration. Depression of XII nerve activity by opioid analgesics is a significant clinical problem, but underlying mechanisms are poorly understood. Currently there are no suitable pharmacological approaches to counter opiate-induced suppression of XII nerve activity while maintaining analgesia. Ampakines accentuate alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA receptor responses. The AMPA family of glutamate receptors mediate excitatory transmission to XII motoneurons. Therefore the objectives were to determine whether the depressant actions of mu-opioid receptor activation on inspiratory activity includes a direct inhibitory action at the inspiratory premotoneuron to XII motoneuron synapse, and to identify underlying mechanism(s. We then examined whether ampakines counteract opioid-induced depression of XII motoneuron activity. METHODOLOGY/PRINCIPAL FINDINGS: A medullary slice preparation from neonatal rat that produces inspiratory-related output in vitro was used. Measurements of inspiratory burst amplitude and frequency were made from XII nerve roots. Whole-cell patch recordings from XII motoneurons were used to measure membrane currents and synaptic events. Application of the mu-opioid receptor agonist, DAMGO, to the XII nucleus depressed the output of inspiratory XII motoneurons via presynaptic inhibition of excitatory glutamatergic transmission. Ampakines (CX614 and CX717 alleviated DAMGO-induced depression of XII MN activity through postsynaptic actions on XII motoneurons. CONCLUSIONS/SIGNIFICANCE: The inspiratory-depressant actions of opioid analgesics include presynaptic inhibition of XII motoneuron output. Ampakines counteract mu-opioid receptor-mediated depression of XII motoneuron inspiratory activity. These results suggest that ampakines may be beneficial in countering opiate

  5. 阿片类毒品对HIV-1感染者PBMCs中TLR9基因表达的影响%Influence of Opiate Abuse on Expression of Toll-like Receptor 9 in Peripheral Blood Mononuclear Cells of HIV-1-Infected Individuals

    Institute of Scientific and Technical Information of China (English)

    潘沛江; 韦富梅; 蒋俊俊; 梁冰玉; 黄颉刚; 廖艳研; 苏锦明; 李彧; 杨小艺

    2015-01-01

    探讨滥用阿片类毒品(Opiates)对Ⅰ型艾滋病病毒(Human immunodeficiency virus,HIV-1)感染者外周血单个核细胞(PBMCs)中TLR9基因表达水平的影响,为阐明阿片类毒品促进HIV-1复制的作用机制奠定基础.首先在南宁、柳州、钦州市地区的美沙酮、艾滋病自愿咨询检测门诊招募对象,经研究对象知情同意,分为4组,即阿片类毒品滥用的HIV-1感染组(Opiates HIV(+)组)、阿片类毒品滥用非HIV-1感染组(Opiates HIV(-)组)、非阿片类毒品滥用的HIV感染组(Non-opiates HIV(+)组)和健康对照组(Control组),每组随机招募50人.其次,以问卷形式调查对象的人口学特征,并采集其外周静脉血,分离出PBMCs后提取RNA.最后采用qPCR、蛋白质印迹法(Western blot,WB)法检测4组人群PBMCs中TLR9的mRNA、蛋白表达水平.经调查发现4组人群在年龄、性别、民族、户籍所在地、婚姻状况、文化程度和吸毒年限等人口学特征方面差异均无统计学意义(P>0.05).Opiates HIV(+)与Non Opiates HIV(+)组病毒载量中位数分别为4.450×103和3.977×103 cp/mL,差异有统计学意义(P<0.05).TLR9 mRNA相对表达量在Opiates HIV(+)、Non-Opiates HIV(+)、Opiates HIV(-)和Control组中分别为(2.13±1.59)×10-3、(3.66±2.22)×10-3、(1.96±1.42)× 10-3和(7.66±4.87)×10-3.阿片类毒品滥用和HIV感染对TLR9的表达存在交互作用(F=25.91,P=0.000).经单独效应分析,HIV阳性与阴性人群中,阿片类毒品滥用者TLR9相对表达量均明显低于非毒品滥用者(P<0.05);在吸毒人群中,HIV阳性者与HIV阴性者两组间差异没有统计学意义(P>0.05);在不吸毒人群中,HIV阳性者低于正常组,两组间差异有统计学意义(P<0.05).WB的结果显示,Opiates HIV(+)、Non-Opiates HIV(+)、Opiates HIV(-)三组TLR9蛋白的表达量均低于Control组.上述结果表明阿片类毒品能够下调HIV-1感染者PBMCs中TLR9的表达水平,提示阿片类毒品可能通过影响TLR9

  6. Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli.

    OpenAIRE

    NAKAGAWA, Akira; Matsumura, Eitaro; Koyanagi, Takashi; Katayama, Takane; Kawano, Noriaki; Yoshimatsu, Kayo; Yamamoto, Kenji; Kumagai, Hidehiko; Sato, Fumihiko; Minami, Hiromichi

    2016-01-01

    Opiates such as morphine and codeine are mainly obtained by extraction from opium poppies. Fermentative opiate production in microbes has also been investigated, and complete biosynthesis of opiates from a simple carbon source has recently been accomplished in yeast. Here we demonstrate that Escherichia coli serves as an efficient, robust and flexible platform for total opiate synthesis. Thebaine, the most important raw material in opioid preparations, is produced by stepwise culture of four ...

  7. Add-on gabapentin in the treatment of opiate withdrawal.

    Science.gov (United States)

    Martínez-Raga, José; Sabater, Ana; Perez-Galvez, Bartolome; Castellano, Miguel; Cervera, Gaspar

    2004-05-01

    Gabapentin is an antiepileptic drug shown to be effective in the treatment of pain disorders and appears to be useful as well for several psychiatric disorders, including bipolar disorder, anxiety disorders, alcohol withdrawal and cocaine dependence. Gabapentin, at a dose of 600 mg three times a day, was evaluated as an add-on medication to a standard detoxification regime in seven heroin dependent individuals undergoing outpatient opiate withdrawal treatment. All seven patients successfully completed opiate detoxification and commenced opiate antagonist treatment with naltrexone on day five of withdrawal treatment, as scheduled. No adverse event was noted. Gabapentin appeared to lead a reduction in symptomatic medication and an overall beneficial effect on symptoms of heroin withdrawal.

  8. Pholcodine interference in the immunoassay for opiates in urine.

    Science.gov (United States)

    Svenneby, G; Wedege, E; Karlsen, R L

    1983-01-01

    The excretion in urine after single oral therapeutic doses of morphine derivatives was analysed with radioimmunoassay (RIA) and homogeneous enzyme immunoassay (EMIT) for opiates. In contrast to the rapid excretion of ethylmorphine and codeine, pholcodine showed positive results for opiates 2-6 weeks after intake when the urines were analysed with the RIA-method. When analysed with the EMIT-method, positive results were obtained for pholcodine for approximately 10 days. As pholcodine is a common component in cough mixtures, its prolonged excretion could represent a hazard in interpreting the results from drug analyses of urines.

  9. Photoperiodic changes in opiate binding and their functional implications in golden hamsters.

    Science.gov (United States)

    Tubbiola, M L; Nock, B; Bittman, E L

    1989-11-27

    Daylength modulates gonadotropin secretion, gonadal steroid hormone feedback, sexual behavior and body weight in male golden hamsters. Endogenous opiates regulate each of these phenomena, and the ability of opiate receptor blockade to elevate serum LH secretion is photoperiod-dependent. We used in vitro autoradiography to localize and quantify effects of daylength in golden hamsters. Hamsters were exposed to stimulatory (14 h light: 10 h dark) or inhibitory (10 h light: 14 h dark) photoperiods for 10 weeks before specific [3H]naloxone binding was assessed. Short days significantly decreased binding in medial amygdala and the intercalated amygdaloid nucleus. This effect was reversed by superior cervical ganglionectomy. No significant effects of daylength were observed in other amygdaloid, hypothalamic or preoptic areas. Lesions of the medial amygdala decreased copulatory behavior, short day-induced weight loss, and anogenital chemoinvestigation but did not affect gonadal regression or other forms of chemoinvestigation. These lesions facilitated testosterone's negative feedback on luteinizing hormone in long days but did not interfere with the potentiation of negative feedback by short days.

  10. Reinforcement processes in opiate addiction: a homeostatic model.

    Science.gov (United States)

    Schulteis, G; Koob, G F

    1996-11-01

    The development of tolerance and dependence has traditionally been considered an integral aspect of the drug addiction process, and opiate dependence has been studied extensively as a model system in this regard. However, recent emphasis on the positive reinforcing properties of drugs has led to the suggestion that tolerance, dependence, and withdrawal may be of secondary or even negligible importance in motivating compulsive drug use. The current article argues for an integrated view of addiction in the form of a homeostatic neuroadaptation model which emphasizes the motivational significance of both the positive affective state produced by opiates and the negative affective state characteristic of drug withdrawal. The model is supported by evidence at both the behavioral and neural systems levels of analysis. Understanding the important distinction between somatic and affective components of opiate withdrawal is key to recognizing the factors which contribute to the motivational significance of opiate dependence and withdrawal. In addition, the critical role of conditioning processes in the maintenance of compulsive drug use and relapse after periods of abstention is discussed. Finally, it is argued that both the positive reinforcement produced by acute administration of a drug and the negative affective state produced by withdrawal are common to multiple classes of abused drugs, suggesting that an understanding of homeostatic neuroadaptation within motivational systems provides a key to the etiology, treatment and prevention of drug addiction.

  11. Opiate Injection Site Infections--19 years in the UK

    Centers for Disease Control (CDC) Podcasts

    2017-09-06

    Dan Lewer, a public health registrar in England, discusses an increase in infections related to opiate injections in the U.K.  Created: 9/6/2017 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 9/6/2017.

  12. Lapse and relapse following inpatient treatment of opiate dependence.

    LENUS (Irish Health Repository)

    Smyth, B P

    2010-06-01

    We conducted a prospective follow-up study of consecutive opiate dependent patients admitted to a residential addiction treatment service for detoxification. We measured the rate of relapse following discharge, and sought to identify factors that were associated with early relapse (i.e., a return to daily opiate use). Follow-up interviews were conducted with 109 patients, of whom, 99 (91%) reported a relapse. The initial relapse occurred within one week in 64 (59%) cases. Multivariate survival analysis revealed that earlier relapse was significantly predicted by younger age, greater heroin use prior to treatment, history of injecting, and a failure to enter aftercare. Unexpectedly, those who were in a relationship with an opiate user had significantly delayed relapse. Those who completed the entire six-week inpatient treatment programme also had a significantly delayed relapse. In order to reduce relapse and the associated increased risk of fatal overdose, services providing residential opiate detoxification should prepare people for admission, strive to retain them in treatment for the full admission period and actively support their entry into planned aftercare in order to improve outcome.

  13. Traditional Chinese medicine in treatment of opiate addiction

    Institute of Scientific and Technical Information of China (English)

    Jie SHI; Yan-li LIU; Yu-xia FANG; Guo-zhu XU; Hai-fen ZHAI; Lin LU

    2006-01-01

    Traditional Chinese medicine (TCM) includes Chinese medicine and acupuncture. Chinese medicine consists of natural products including plants, animals and minerals. TCM has been practiced in China for more than 2000 years, and for the past 200 years has been used in treatment of drug addiction. Ten Chinese medicines for the treatment of opiate addiction have been approved by the Chinese State Food and Drug Administration (SFDA), and at least 6 are in clinical trials. The general therapeutic principle of Chinese medicine developed was based on its unique theory of "reinforcing healthy Qi and resolving and removing effects of toxicity". Acupuncture, another essential part of TCM, which was developed based on the principle that "functions of the human body are controlled by the 'Jing-Luo' and 'Qi-Xue' system", has been used not only in China, but also in Europe, the USA and other countries, for controlling opiate addiction. There are some advantages in using TCM for opiate detoxification, including less harmful side effects, high safety and ideal effects in the inhibition of protracted withdrawal symptoms and relapse. Co-administration of TCM with modern medicine shows some synergistic effects in detoxification. Many TCM for detoxification also have efficacy in the rehabilitation of abnormal body functions induced by chronic drug use, including improving immune function, increasing working memory and preventing neurological disorder. Given that TCM is effective in the prevention of relapse and causes fewer side effects, it may be used widely in the treatment of opiate addiction.

  14. Changes in reward-induced brain activation in opiate addicts

    NARCIS (Netherlands)

    Martin-Soelch, C; Chevalley, AF; Kunig, G; Missimer, J; Magyar, S; Mino, A; Schultz, W; Leenders, KL

    2001-01-01

    Many studies indicate a role of the cerebral dopaminergic reward system in addiction. Motivated by these findings, we examined in opiate addicts whether brain regions involved in the reward circuitry also react to human prototypical rewards. We measured regional cerebral blood flow (rCBF) with

  15. Contingent methadone delivery: effects on illicit-opiate use.

    Science.gov (United States)

    Higgins, S T; Stitzer, M L; Bigelow, G E; Liebson, I A

    1986-07-01

    This study examined the effects of contingent vs. non-contingent delivery of a methadone dose supplement on relapse to illicit opiate use in the context of a methadone outpatient detoxification program. Following a 3-week methadone stabilization period on 30 mg, patients (N = 39) were randomly assigned to a contingent, a non-contingent, or a control treatment group. All patients received identical gradual reductions in their assigned methadone dose. During the dose reduction period (weeks 4-11), members of the contingent (N = 13) and non-contingent groups (N = 13) could obtain daily methadone-dose supplements up to 20 mg, but contingent group members could obtain supplements only if their most recent urinalysis results were opiate negative. Control subjects (N = 13) did not have dose increases available. The contingent group presented significantly lower opiate-positive urines during weeks 8-11 (14% positive) of the detox than the non-contingent (38% positive) or control (50% positive) groups. Additionally, the availability of extra methadone improved treatment retention and increased clinic attendance above levels observed in the control group. The potential for further use of methadone's reinforcing properties in the treatment of opiate dependence is discussed.

  16. Changes in reward-induced brain activation in opiate addicts

    NARCIS (Netherlands)

    Martin-Soelch, C; Chevalley, AF; Kunig, G; Missimer, J; Magyar, S; Mino, A; Schultz, W; Leenders, KL

    2001-01-01

    Many studies indicate a role of the cerebral dopaminergic reward system in addiction. Motivated by these findings, we examined in opiate addicts whether brain regions involved in the reward circuitry also react to human prototypical rewards. We measured regional cerebral blood flow (rCBF) with (H2O)

  17. Pain reporting, opiate dosing, and the adverse effects of opiates after hip or knee replacement in patients 60 years old or older.

    Science.gov (United States)

    Petre, Benjamin M; Roxbury, Christopher R; McCallum, Jeremy R; Defontes, Kenneth W; Belkoff, Stephen M; Mears, Simon C

    2012-03-01

    Our goal was to determine whether there were age-related differences in pain, opiate use, and opiate side effects after total hip or knee arthroplasty in patients 60 years old or older. We hypothesized that there would be no significant differences between age groups in (1) mean pain score, (2) opiate use after adjusting for pain, or (3) opiate side effects after adjusting for opiate use and pain score. We retrospectively reviewed the electronic and paper charts of all patients undergoing total joint replacements at our institution over 3 years who met the following criteria: (1) 60 years old or older, (2) primary single total knee or total hip replacement, and (3) no preoperative dementia. Preoperative, intraoperative, and postoperative course data were collected using a customized data entry process and database. We divided the patients into 2 age groups, those 60 to 79 years old and those 80 years old or older. Using a marginal model with the panel variable of postoperative day, we investigated the associations between age group and pain, age group and pain adjusting for opiate use, and age group and complications (respiratory depression, naloxone usage as a measure of respiratory arrest, delirium, constipation, and urinary retention) adjusting for opiate use (Xtgee, Stata10, Stata Corp. LP, College Station, Texas). Significance was set at P opiates prescribed yet significantly more side effects, including delirium (odds ratio 4.2), than did the younger group, even after adjusting for opiate dose and pain score.

  18. Estimate of the extent of opiate overdose in Ukraine

    Directory of Open Access Journals (Sweden)

    Andreeva, Tatiana

    2012-07-01

    Full Text Available BACKGROUND: Overdose is known to be among leading causes of death in injection drug users (IDUs. However, there is no official statistics in Ukraine with regard to both fatal and nonfatal overdose. We aimed to estimate the scope of the problem and level of provided help to those who have suffered overdose.METHODS: Data from bio-behavioral survey conducted among IDUs in 2007 (N=8575 with general questions about having experienced overdose and specialized survey among participants of overdose prevention and response program conducted in 2010 (N=2821 were considered. The specialized survey inquired personal experience of overdose and received help, witnessing overdose in others and providing help. Data triangulation was used to estimate the scope of the problem.RESULTS: Among the participants of the specialized survey, 1918 witnessed overdoses and 550 of them said that help was delivered late. Thus, up to 29% of overdoses could be fatal.According to the results of the bio-behavioral survey, 35-37% of self-prepared opiates users have ever experienced overdose, while among all IDUs current opiate users constitute 53% and 80% are ever users. Among the participants of the specialized survey, a larger proportion are current opiate users (73%, and 70% have ever suffered overdose with 19% within the last six months. Of 1201 opiate overdoses reported by the participants of the specialized survey, 179 have reported to have received specific treatment with naloxone which constitutes 15%. With estimated number of IDUs in Ukraine around 300 thousand, this makes 159 thousand opiate users, 57 thousand those who have ever suffered overdose and 15 thousand those who suffered overdose within last six months. Of these, 4 thousand could have died and 2 thousand could have received specific treatment with naloxone.CONCLUSION: We estimate that 30 thousand nonfatal and 8 thousand fatal overdoses may happen in Ukraine per year.

  19. Nanotherapeutic approach for opiate addiction using DARPP-32 gene silencing in an animal model of opiate addiction.

    Science.gov (United States)

    Ignatowski, T A; Aalinkeel, R; Reynolds, J L; Nair, B B; Sykes, D E; Gleason, C P K; Law, W C; Mammen, M J; Prasad, P N; Schwartz, S A; Mahajan, Supriya D

    2015-03-01

    Opiates act on the dopaminergic system of the brain and perturb 32 kDa dopamine and adenosine 3', 5'-monophosphate-regulated phosphoprotein (DARPP-32) function. The DARPP-32 mediated inhibition of protein phosphatase-1 (PP-1) and modulation of transcriptional factor CREB is critical to the changes in neuronal plasticity that result in behavioral responses during drug abuse. To investigate the role of DARPP-32 mediated signaling on withdrawal behavior in a rat model of opiate addiction, we used intracerebral administration of gold nanorods (GNR) complexed to DARPP-32 siRNA to silence DARPP-32 gene expression and measure its effects on the opiate withdrawal syndrome. We hypothesized that DARPP-32 siRNA will suppress the neurochemical changes underlying the withdrawal syndrome and therefore prevent conditioned place aversion by suppressing or removing the constellation of negative effects associated with withdrawal, during the conditioning procedure. Our results showed that opiate addicted animals treated with GNR-DARPP-32 siRNA nanoplex showed lack of condition place aversive behavior consequent to the downregulation of secondary effectors such as PP-1 and CREB which modify transcriptional gene regulation and consequently neuronal plasticity. Thus, nanotechnology based delivery systems could allow sustained knockdown of DARPP-32 gene expression which could be developed into a therapeutic intervention for treating drug addiction by altering reward and motivational systems and interfere with conditioned responses.

  20. Pharmacogenetics of opiates in clinical practice: the visible tip of the iceberg.

    Science.gov (United States)

    Hajj, Aline; Khabbaz, Lydia; Laplanche, Jean-Louis; Peoc'h, Katell

    2013-04-01

    Opioids are the cornerstone of analgesic therapy and are used as a substitution therapy for opiate addiction. Interindividual variability in response to opioids is a significant challenge in the management of pain and substitution. Therefore, treatment with opioids requires a careful individualization of dosage to achieve an appropriate balance of efficacy and adverse effects and, consequently, avoid toxicity, particularly respiratory depression, sedation and for some, cardiac ventricular fibrillations. Many studies have investigated the association between genetic factors and the variability of response to opioids. Variants in genes encoding proteins implied in opioid pharmacokinetics (absorption, distribution, metabolism, excretion and toxicity), together with those implied in opioids direct and indirect pharmacodynamics (genes of opioid receptors and monoaminergic systems), are the most studied. Many association studies have not been replicated. The purpose of this article is to summarize pharmacogenetic data associated with some opioids frequently encountered in managed care settings.

  1. Delta-opiate DPDPE in magnetically oriented phospholipid micelles: binding and arrangement of aromatic pharmacophores.

    Science.gov (United States)

    Rinaldi, F; Lin, M; Shapiro, M J; Petersheim, M

    1997-01-01

    D-Penicillamine(2,5)-enkephalin (DPDPE) is a potent opioid peptide that exhibits a high selectivity for the delta-opiate receptors. This zwitterionic peptide has been shown, by pulsed-field gradient 1H NMR diffusion studies, to have significant affinity for a zwitterionic phospholipid bilayer. The bilayer lipid is in the form of micelles composed of dihexanoylphosphatidylcholine (DHPC) and dimyristoylphosphatidylcholine (DMPC) mixtures, where the DMPC forms the bilayer structure. At high lipid concentration (25% w/w) these micelles orient in the magnetic field of an NMR spectrometer. The resulting 1H-13C dipolar couplings and chemical shift changes in the natural abundance 13C resonances for the Tyr and Phe aromatic rings were used to characterize the orientations in the bilayer micelles of these two key pharmacophores. Images FIGURE 1 FIGURE 8 PMID:9414244

  2. Analysis of the clinical indications for opiate use in inflammatory bowel disease

    Science.gov (United States)

    Khan, Sundas; Akerman, Meredith; Sultan, Keith

    2017-01-01

    Background/Aims Opiate use for inflammatory bowel disease (IBD), particularly high-dose (HD) use, is associated with increased mortality. It's assumed that opiate use is directly related to IBD-related complaints, although this hasn't been well defined. Our goal was to determine the indications for opiate use as a first step in developing strategies to prevent or decrease opiate use. Methods A retrospective cohort was formed of adults who were diagnosed with IBD and for whom outpatient evaluations from 2009 to 2014 were documented. Opiate use was defined if opiates were prescribed for a minimum of 30 days over a 365-day period. Individual chart notes were then reviewed to determine the clinical indication(s) for low-dose (LD) and HD opiate use. Results After a search of the electronic records of 1,109,277 patients, 3,226 patients with IBD were found. One hundred four patients were identified as opiate users, including 65 patients with Crohn's and 39 with ulcerative colitis; a total of 134 indications were available for these patients. IBD-related complaints accounted for 49.25% of the opiate indications, with abdominal pain (23.13%) being the most common. Overall, opiate use for IBD-related complaints (81.40% vs. 50.82%; P=0.0014) and abdominal pain (44.19% vs. 19.67%; P=0.0071) was more common among HD than among LD. Conclusions Our findings show that most IBD patients using opiates, particularly HD users, used opiates for IBD-related complaints. Future research will need to determine the degree to which these complaints are related to disease activity and to formulate non-opiate pain management strategies for patients with both active and inactive IBD. PMID:28239317

  3. Impact of Spouse's Opiate Dependence on the Partner's

    Directory of Open Access Journals (Sweden)

    Roya Noori

    2008-12-01

    Full Text Available Objective: We aimed to evaluate the influence of drug dependency on sexual function of wives of opium addicts.Materials and methods: In a cross-sectional study, 150 wives of opiate dependent men were assessed for the impact of drug addiction. Sociodemographic factors like age, educational level, job, marital duration and having child were evaluated. Sexual function was measured using relationship and sexuality scale (RSS. Results: Approximately 73% of the participitants were sexually active with having at least one intercourse in the last 2 weeks, and approximately half of the participitants had unsatisfied intercourse. About ninety percent reported negative effect of the addiction on their sexual life. After the spouse addiction, sexual desire, ability to reach orgasm and frequency of sexual intercourse were decreased in 73%, 64% and 67.3%, respectively. Conclusion: The wives of opiate addicts believe that their sexual function has been impaired by the addiction of their husbands.

  4. Opiate versus psychostimulant addiction: the differences do matter.

    Science.gov (United States)

    Badiani, Aldo; Belin, David; Epstein, David; Calu, Donna; Shaham, Yavin

    2011-10-05

    The publication of the psychomotor stimulant theory of addiction in 1987 and the finding that addictive drugs increase dopamine concentrations in the rat mesolimbic system in 1988 have led to a predominance of psychobiological theories that consider addiction to opiates and addiction to psychostimulants as essentially identical phenomena. Indeed, current theories of addiction - hedonic allostasis, incentive sensitization, aberrant learning and frontostriatal dysfunction - all argue for a unitary account of drug addiction. This view is challenged by behavioural, cognitive and neurobiological findings in laboratory animals and humans. Here, we argue that opiate addiction and psychostimulant addiction are behaviourally and neurobiologically distinct and that the differences have important implications for addiction treatment, addiction theories and future research.

  5. Expansion of opiate agonist treatment: an historical perspective

    Directory of Open Access Journals (Sweden)

    Newman Robert G

    2006-07-01

    Full Text Available Abstract Untreated opiate addiction remains a major health care crisis in New York and in most other urban centers in America. Optimism for closing the gap between need and demand for treatment and its availability has greeted the recent approval of a new opiate medication for addiction, buprenorphine – which unlike methadone may be prescribed by independent, office-based practitioners. The likelihood of buprenorphine fulfilling its potential is assessed in the light of the massive expansion of methadone treatment more than 30 years earlier. It is concluded that the key, indispensable ingredient of success will be true commitment on the part of Government to provide care to all those who need it.

  6. Thermal latency studies in opiate-treated mice

    OpenAIRE

    Noam Schildhaus; Eliana Trink; Chirs Polson; Louis DeTolla; Tyler, Betty M.; Jallo, George I.; Sino Tok; Michael Guarnieri

    2014-01-01

    Background: The change in the reaction time of a tail or paw exposed to a thermal stimulus is a measure of nociceptive activity in laboratory animals. Tail-flick and plantar thermal sensitivity (Hargreaves) tests are non-invasive, minimize stress, and can be used to screen animals for phenotype and drug activity. Objective: Hargreaves testing has been widely used in rats. We investigated its use to measure the activity of opiate analgesia in mice. Methods: Mice were used in thermal stimulus s...

  7. Policy Progress for Physician Treatment of Opiate Addiction

    OpenAIRE

    Merrill, Joseph O.

    2002-01-01

    Medical treatment of heroin addiction with methadone and other pharmacotherapies has important benefits for individuals and society. However, regulatory policies have separated this treatment from the medical care system, limiting access to care and contributing to the social stigma of even effective addiction pharmacotherapy. Increasing problems caused by heroin addiction have added urgency to the search for policies and programs that improve the access to and quality of opiate addiction tre...

  8. Thermal latency studies in opiate-treated mice

    Directory of Open Access Journals (Sweden)

    Noam Schildhaus

    2014-01-01

    Full Text Available Background: The change in the reaction time of a tail or paw exposed to a thermal stimulus is a measure of nociceptive activity in laboratory animals. Tail-flick and plantar thermal sensitivity (Hargreaves tests are non-invasive, minimize stress, and can be used to screen animals for phenotype and drug activity. Objective: Hargreaves testing has been widely used in rats. We investigated its use to measure the activity of opiate analgesia in mice. Methods: Mice were used in thermal stimulus studies at 1-5 hours and 1-5 days to test acute and extended release preparations of buprenorphine. Results: Hargreaves testing had limited value at 1-5 hours because mice can have an obtunded response to opiate therapy. Tail-flick studies with restrained mice are not affected by the initial locomotor stimulation. Discussion: The present report describes a simple restraint system for mice. The utility of the system is demonstrated by examining the efficacy of acute and extended release buprenorphine injections in Balb/c and Swiss mice. Conclusion: Standardized tail-flick testing provides a sensitive robust method to monitor opiate activity in mice.

  9. Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli.

    Science.gov (United States)

    Nakagawa, Akira; Matsumura, Eitaro; Koyanagi, Takashi; Katayama, Takane; Kawano, Noriaki; Yoshimatsu, Kayo; Yamamoto, Kenji; Kumagai, Hidehiko; Sato, Fumihiko; Minami, Hiromichi

    2016-02-05

    Opiates such as morphine and codeine are mainly obtained by extraction from opium poppies. Fermentative opiate production in microbes has also been investigated, and complete biosynthesis of opiates from a simple carbon source has recently been accomplished in yeast. Here we demonstrate that Escherichia coli serves as an efficient, robust and flexible platform for total opiate synthesis. Thebaine, the most important raw material in opioid preparations, is produced by stepwise culture of four engineered strains at yields of 2.1 mg l(-1) from glycerol, corresponding to a 300-fold increase from recently developed yeast systems. This improvement is presumably due to strong activity of enzymes related to thebaine synthesis from (R)-reticuline in E. coli. Furthermore, by adding two genes to the thebaine production system, we demonstrate the biosynthesis of hydrocodone, a clinically important opioid. Improvements in opiate production in this E. coli system represent a major step towards the development of alternative opiate production systems.

  10. Modulation of opiate-related signaling molecules in morphine-dependent conditioned behavior: conditioned place preference to morphine induces CREB phosphorylation.

    Science.gov (United States)

    Morón, José A; Gullapalli, Srinivas; Taylor, Chirisse; Gupta, Achla; Gomes, Ivone; Devi, Lakshmi A

    2010-03-01

    Opiate addiction is a chronic, relapsing behavioral disorder where learned associations that develop between the abused opiate and the environment in which it is consumed are brought about through Pavlovian (classical) conditioning processes. However, the signaling mechanisms/pathways regulating the mechanisms that underlie the responses to opiate-associated cues or the development of sensitization as a consequence of repeated context-independent administration of opiates are unknown. In this study we examined the phosphorylation levels of various classic signaling molecules in brain regions implicated in addictive behaviors after acute and repeated morphine administration. An unbiased place conditioning protocol was used to examine changes in phosphorylation that are associated with (1) the expression of the rewarding effects of morphine and (2) the sensitization that develops to this effect. We also examined the effects of a delta-receptor antagonist on morphine-induced conditioned behavior and on the phosphorylation of classic signaling molecules in view of data showing that blockade of delta-opioid receptor (deltaOR) prevents the development of sensitization to the rewarding effects of morphine. We find that CREB phosphorylation is specifically induced upon the expression of a sensitized response to morphine-induced conditioned behavior in brain areas related to memory consolidation, such as the hippocampus and cortex. A similar effect is also observed, albeit to a lesser extent, in the case of the GluR1 subunit of AMPA glutamate receptor. These increases in the phosphorylation levels of CREB and pGluR1 are significantly blocked by pretreatment with a deltaOR antagonist. These results indicate a critical role for phospho-CREB, AMPA, and deltaOR activities in mediating the expression of a sensitized response to morphine-dependent conditioned behavior.

  11. More mysteries of opium reveal'd: 300 years of opiates.

    Science.gov (United States)

    Miller, R J; Tran, P B

    2000-08-01

    This year is the 300th anniversary of the publication of one of the first books written about opiates and their subjective effects. Since that time the influence of opiates in Western society has grown enormously, as has our knowledge of the mechanisms by which these drugs produce their effects. Wars have been fought over the use of opiates and the economies of several countries depend on their production. In this article, some aspects of the history and effects of opiates on the arts in particular are explored.

  12. Asymmetric dimethylarginine (ADMA)--a modulator of nociception in opiate tolerance and addiction?

    Science.gov (United States)

    Kielstein, Anousheh; Tsikas, Dimitrios; Galloway, Gantt P; Mendelson, John E

    2007-09-01

    Nitric oxide (NO) is generated from l-arginine by NO synthases, of which three forms have been identified: endothelial, inducible and neuronal (eNOS, iNOS and nNOS, respectively). The l-arginine metabolite asymmetric dimethylarginine (ADMA) is a potent, noncompetitive inhibitor of nNOS, while its congener N(G)-monomethyl-l-arginine (l-NMMA) is a less potent, competitive inhibitor. In rat neurons large amounts of ADMA are found, suggesting its importance in modulating neuronal activity. Humans generate approximately 300mumol ( approximately 60mg) ADMA per day. It is released from myelin basic proteins that are highly expressed in neuronal tissue. ADMA is mainly degraded by the action of the enzyme dimethylarginine dimethylaminohydrolase (DDAH), which exists in two isoforms. DDAH1 is highly expressed in brain, suggesting specific function in this area. The presence of nNOS and DDAH1 in brain suggests that ADMA may have specific CNS activity and be more than an unregulated metabolite. Increased NO production-either prior to or concurrently with opioid administration-results in an enhanced rate and extent of development of tolerance to morphine in mice. NO produces an alteration in the mu-opioid receptor that increases constitutive receptor activity. It thereby reduces the ability of a selective mu-opioid agonist to activate the mu-opioid receptor; these in vitro molecular effects occur in a time course consistent with the in vivo development of antinociceptive tolerance in mice. Amongst many other synthetic NOS inhibitors of varying specificity, 7-nitroindazole (7-NI) has been shown to have a high affinity (IC(50) 0.71 microM) to nNOS. Selective blockade of nNOS by 7-NI attenuated morphine withdrawal in opiate dependent rats, suggesting nNOS as a viable target for development of pharmacotherapies. We hypothesize that, by inhibiting nNOS and reducing NO levels, ADMA may decrease mu-opiate receptor constitutive activity, resulting in alteration of the analgesic dose

  13. Pharmacological modulation of protein kinases as a new approach to treat addiction to cocaine and opiates.

    Science.gov (United States)

    García-Pardo, María Pilar; Roger-Sanchez, Concepción; Rodríguez-Arias, Marta; Miñarro, Jose; Aguilar, María Asunción

    2016-06-15

    Drug addiction shares brain mechanisms and molecular substrates with learning and memory processes, such as the stimulation of glutamate receptors and their downstream signalling pathways. In the present work we provide an up-to-date review of studies that have demonstrated the implication of the main memory-related calcium-dependent protein kinases in opiate and cocaine addiction. The effects of these drugs of abuse in different animal models of drug reward, dependence and addiction are altered by manipulation of the mitogen-activated protein kinase (MAPK) family, particularly extracellular signal regulated kinase (ERK), calcium/calmodulin-dependent kinase II (CaMKII), the protein kinase C (PKC) family (including PKMζ), cAMP-dependent protein kinase A (PKA), cGMP-dependent protein kinase G (PKG), the phosphatidylinositol 3-kinase (PI3K) pathway and its downstream target mammalian target of Rapamycin (mTOR), cyclin-dependent kinase 5 (Cdk5), heat-shock proteins (Hsp) and other enzymes and proteins. Research suggests that drugs of abuse induce dependence and addiction by modifying the signalling pathways that involve these memory-related protein kinases, and supports the idea that drug addiction is an excessive aberrant learning disorder in which the maladaptive memory of drug-associated cues maintains compulsive drug use and contributes to relapse. Moreover, the studies we review offer new pharmacological strategies to treat opiate and cocaine dependence based on the manipulation of these protein kinases. In particular, disruption of reconsolidation of drug-related memories may have a high therapeutic value in the treatment of drug addiction.

  14. Effects of specific mu and kappa opiate tolerance and abstinence on hypothalamo-pituitary-adrenal axis secretion in the rat.

    Science.gov (United States)

    Ignar, D M; Kuhn, C M

    1990-12-01

    Chronic administration of opiates to rats results in HPA axis tolerance and abstinence-induced hypersecretion. The effects of specific mu and kappa tolerance and withdrawal on the functional secretion of the HPA axis were evaluated in this study. Adult male rats were injected s.c. twice daily with saline, morphine or U50,488 for 5 days. Serum adrenocorticotrophic hormone (ACTH) or corticosterone (CS) were determined by radioimmunoassay as measures of HPA axis function. Tolerance to morphine (10 mg/kg) and U50,488 (1 mg/kg), but no cross-tolerance, was observed suggesting the development of mu- or kappa-specific tolerance, respectively. Tolerance does not occur at the pituitary or adrenal levels after these paradigms because ACTH and CS responses to exogenous corticotropin-releasing factor and ACTH, respectively, were not attenuated. CS secretion in response to novelty stress was not affected by either chronic opiate treatment, but the circadian variation of CS levels was slightly blunted after chronic morphine. In contrast, the elevation of CS secretion by quipazine (0.5 mg/kg) and physostigmine (0.1 mg/kg) was attenuated after chronic U50,488, but not morphine administration. Both spontaneous and antagonist-precipitated withdrawal from morphine, but not U50,488, resulted in elevation of CS levels. Low doses of morphine suppressed morphine abstinence-induced CS hypersecretion, whereas, U50,488 and clonidine had no effect. In conclusion, alterations of HPA axis function occur during chronic mu or kappa opiate administration that are receptor-specific and involve multiple neural controls of the HPA axis.

  15. Screening of cannabinoids, benzoylecgonine and opiates in whole blood and urine using emit II plus immunoassay and konelab 30

    DEFF Research Database (Denmark)

    Simonsen, Kirsten Wiese; Christiansen, Nobuko; Müller, Irene Breum

    2004-01-01

    Screening,cannabinoids,benzoylecgonine,opiates in whole blood and urine, emit II, immunoassay,konelab 30......Screening,cannabinoids,benzoylecgonine,opiates in whole blood and urine, emit II, immunoassay,konelab 30...

  16. The opiate antagonist, naltrexone, in the treatment of trichotillomania

    DEFF Research Database (Denmark)

    Grant, Jon E; Odlaug, Brian Lawrence; Schreiber, Liana R N;

    2014-01-01

    Trichotillomania (TTM) is characterized by repetitive hair pulling resulting in hair loss. Data on the pharmacological treatment of TTM are limited. This study examined the opioid antagonist, naltrexone, in adults with TTM who had urges to pull their hair. Fifty-one individuals with TTM were...... improved with naltrexone (P = 0.026). Subjects taking naltrexone with a family history of addiction showed a greater numerical reduction in the urges to pull, although it was not statistically significant. Future studies will have to examine whether pharmacological modulation of the opiate system may...

  17. Knowledge of Medical Students, Residents, and Attending Physicians About Opiate Abuse.

    Science.gov (United States)

    Shine, Daniel, Demas, Penelope

    1984-01-01

    A questionnaire concerning knowledge of opiate abuse and attitudes about abusers was administered to 94 randomly selected physicians and medical students at Montefiore Medical Center in New York City. The results indicated that physicians might benefit from improved teaching in the area of opiate abuse. (Author/MLW)

  18. Reinforcement-based outpatient treatment for opiate and cocaine abusers.

    Science.gov (United States)

    Katz, E C; Gruber, K; Chutuape, M A; Stitzer, M L

    2001-01-01

    A reinforcement-based intensive outpatient treatment was delivered to 37 recently detoxified, inner city, heroin and/or cocaine abusers who did not want methadone treatment. Attendance was scheduled and urine collected daily for the first 2 weeks, four times weekly for the next 2 weeks, and then thrice weekly for the final 8 weeks. As attendance incentives, patients received transportation assistance (bus tokens), and $28-$30 per week in vouchers to be spent on activities/items chosen and agreed upon with their counselor. As abstinence incentives, patients received weekend supported recreational activities, lunches, $42-$45 per week in vouchers, and rent or utilities payment ($150 over 4 weeks). Total potential earnings was $1,435 per patient; actual mean earnings was $583. Forty-three percent (n=16) completed 10 or more weeks of treatment. These 16 long-stay patients submitted 92% (SD=19) opiate- and cocaine-negative urines during their enrollment compared with 56% (SD=42) drug-negative urines submitted by 21 drop-outs, F(1,35)=9.99, p=0.003. Overall, 32% of clients became employed during their treatment episode; 94% of long-stay patients were employed at the end of their treatment episode. Patients who were drug-positive at intake were highly likely to drop out. Treatment outcomes compare favorably with those reported in the literature for outpatient nonmethadone treatment of opiate and cocaine abusers. Continued evaluation of this new treatment appears warranted.

  19. GCD quantitation of opiates as propionyl derivatives in blood.

    Science.gov (United States)

    Mykkänen, S; Seppälä, J; Ariniemi, K; Lillsunde, P

    2000-03-01

    We describe a method using a gas chromatograph with electron ionization detection (GCD) for the simultaneous determination of morphine, codeine, 6-monoacetylmorphine, ethylmorphine, and dihydrocodeine in blood. The method employs propionic anhydride in the presence of triethylamine to propionylate free hydroxyl groups of the opiates in blood. The quantitation is achieved by using GCD with selected ion monitoring of the two most characteristic ions for each analyte. The quantitation limit was 0.01 mg/L and the linearity was 0.01-10 mg/L for dihydrocodeine, ethylmorphine, and 6-monoacetylmorphine. For the other investigated opiates, the quantitation limit was 0.025 mg/L and linearity was 0.025-10 mg/L. The intraday relative standard deviation (RSD) varied from 7.2 to 10% at the 0.5 mg/L level, and the day-to-day RSDs varied from 7.5 to 11% at the 0.85 mg/L level.

  20. Binding of kappa- and sigma-opiates in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Wolozin, B.L.; Nishimura, S.; Pasternak, G.W.

    1982-06-01

    Detailed displacements of (/sup 3/H)dihydromorphine by ketocyclazocine and SKF 10,047, (/sup 3/H)ethylketocyclazocine by SKF 10,047, and (/sup 3/H)SKF 10,047 by ketocyclazocine are all multiphasic, suggesting multiple binding sites. After treating brain tissue in vitro with naloxazone, all displacements lose the initial inhibition of /sup 3/H-ligand binding by low concentrations of unlabeled drugs. Together with Scatchard analysis of saturation experiments, these studies suggest a common site which binds mu-, kappa, and sigma-opiates and enkephalins equally well and with highest affinity (KD less than 1 nM). The ability of unlabeled drugs to displace the low affinity binding of (/sup 3/H)dihydromorphine (KD . 3 nM), (/sup 3/H)ethylketocyclazocine (KD . 4 nM), (/sup 3/H)SKF 10,047 (KD . 6 nM), and D-Ala2-D-Leu5-(/sup 3/H)enkephalin (KD . 5 nM) remaining after treating tissue with naloxazone demonstrates unique pharmacological profiles for each. These results suggest the existence of distinct binding sites for kappa- and sigma-opiates which differ from those sites which selectively bind morphine (mu) and enkephalin (delta).

  1. Effect of craving induction on inhibitory control in opiate dependence.

    Science.gov (United States)

    Verdejo-García, Antonio; Lubman, Dan I; Schwerk, Anne; Roffel, Kim; Vilar-López, Raquel; Mackenzie, Trudi; Yücel, Murat

    2012-01-01

    Current neurobiological models of addiction posit that drug seeking is much more likely to occur during emotionally charged states (such as craving), as deficits in inhibitory control become more pronounced during heightened motivational states. The purpose of this study was to examine the effect of cue-induced craving states on attention and inhibitory control within addicted individuals. We tested the performance of 39 opiate-dependent individuals on cognitive measures of attention (Digit Span, Digit Symbol, and Telephone Search) and inhibitory control (Counting Stroop and Go-No-Go) both before and after exposure to an autobiographical craving script. A non-drug using healthy control group (n = 19) performed the same tasks before and after listening to a relaxation tape. Following craving induction, opiate-dependent individuals demonstrated improved performance on tests of processing speed and attentional span (consistent with the practice effect observed in controls) and increased their response errors on the Stroop task (in contrast to controls), while selective attention was unaffected. Individual differences in compulsivity mediated the association between craving and Stroop performance, such that low-compulsive (but not high-compulsive) individuals committed more response errors after craving induction. These findings challenge the notion of cue-induced craving as a primary trigger of disrupted cognition and drug-seeking behavior in addicted individuals, and raise the need to explore individual differences in compulsivity when addressing the links between craving and loss of control within research and clinical settings.

  2. Violent conflict and opiate use in low and middle-income countries: a systematic review.

    Science.gov (United States)

    Jack, Helen; Masterson, Amelia Reese; Khoshnood, Kaveh

    2014-03-01

    Violent conflicts disproportionately affect populations in low and middle-income countries, and exposure to conflict is a known risk factor for mental disorders and substance use, including use of illicit opiates. Opiate use can be particularly problematic in resource-limited settings because few treatment options are available and dependence can impede economic development. In this systematic review, we explore the relationship between violent conflict and opiate use in conflict-affected populations in low and middle-income countries. We searched MEDLINE, PsychINFO, SCOPUS, PILOTS, and select grey literature databases using a defined list of key terms related to conflict and opiate use, screened the results for relevant and methodologically rigorous studies, and conducted a forward search of the bibliographies of selected results to identify additional studies. We screened 707 articles, selecting 6 articles for inclusion: 4 quantitative studies and 2 qualitative studies that examined populations in 9 different countries. All study participants were adults (aged 15-65) living in or displaced from a conflict-affected country. Data sources included death records, hospital records, and interviews with refugees, internally displaced persons, and others affected by conflict. Overall, we found a positive, but ambiguous, association between violent conflict and opiate use, with five of six studies suggesting that opiate use increases with violent conflict. Five key factors mediate the conceptual relationship between opiate use and violent conflict: (1) pre-conflict opiate presence, (2) mental disorders, (3) lack of economic opportunity, (4) changes in social norms or structure, and (5) changes in drug availability. The strength and direction of the association between opiate use and violent conflict and the proposed mediating factors may differ between contexts, necessitating country and population-specific research and interventions. Prevalence of opiate use prior to the

  3. Pharmacological Treatment of Neonatal Opiate Withdrawal: Between the Devil and the Deep Blue Sea

    Directory of Open Access Journals (Sweden)

    Anthony Liu

    2011-01-01

    Full Text Available Illicit drug use with opiates in pregnancy is a major global health issue with neonatal withdrawal being a common complication. Morphine is the main pharmacological agent administered for the treatment of neonatal withdrawal. In the past, morphine has been considered by and large inert in terms of its long-term effects on the central nervous system. However, recent animal and clinical studies have demonstrated that opiates exhibit significant effects on the growing brain. This includes direct dose-dependent effects on reduction in brain size and weight, protein, DNA, RNA, and neurotransmitters—possibly as a direct consequence of a number of opiate-mediated systems that influence neural cell differentiation, proliferation, and apoptosis. At this stage, we are stuck between the devil and the deep blue sea. There are no real alternatives to pharmacological treatment with opiates and other drugs for neonatal opiate withdrawal and opiate addiction in pregnant women. However, pending further rigorous studies examining the potential harmful effects of opiate exposure in utero and the perinatal period, prolonged use of these agents in the neonatal period should be used judiciously, with caution, and avoided where possible.

  4. Cannabis as an adjunct to or substitute for opiates in the treatment of chronic pain.

    Science.gov (United States)

    Lucas, Philippe

    2012-01-01

    There is a growing body of evidence to support the use of medical cannabis as an adjunct to or substitute for prescription opiates in the treatment of chronic pain. When used in conjunction with opiates, cannabinoids lead to a greater cumulative relief of pain, resulting in a reduction in the use of opiates (and associated side-effects) by patients in a clinical setting. Additionally, cannabinoids can prevent the development of tolerance to and withdrawal from opiates, and can even rekindle opiate analgesia after a prior dosage has become ineffective. Novel research suggests that cannabis may be useful in the treatment of problematic substance use. These findings suggest that increasing safe access to medical cannabis may reduce the personal and social harms associated with addiction, particularly in relation to the growing problematic use of pharmaceutical opiates. Despite a lack of regulatory oversight by federal governments in North America, community-based medical cannabis dispensaries have proven successful at supplying patients with a safe source of cannabis within an environment conducive to healing, and may be reducing the problematic use of pharmaceutical opiates and other potentially harmful substances in their communities.

  5. Nonmedical use of sedative-hypnotics and opiates among rural and urban women with protective orders.

    Science.gov (United States)

    Cole, Jennifer; Logan, T K

    2010-07-01

    The purpose of this study was to examine the prevalence and risk factors for lifetime nonmedical use of sedative-hypnotics and opiates among a sample of rural and urban women with recent partner violence victimization (n=756). Nearly one third of the sample (32.8%) reported ever using illicit sedative-hypnotics or opiates. Nonmedical use of sedative-hypnotics and opiates was significantly associated with lifetime cumulative exposure to interpersonal victimization, rural Appalachian residency, past-year use of other substances and other substance-related problems, and lifetime unmet health care needs. Findings have implications for substance abuse prevention and treatment and victim advocacy programs.

  6. Determination of opiates in human fingernail--comparison to hair.

    Science.gov (United States)

    Shen, Min; Chen, Hang; Xiang, Ping

    2014-09-15

    6-Monoacetylmorphine in keratinized matrices can be used to discriminate between heroin users and individuals exposed to other sources of morphine alkaloids. Frozen pulverization is effective in preventing 6-monoacetylmorphine hydrolysis. The main aim of this study was to develop an LC-MS/MS method for the determination of five opiates in human fingernails using a frozen pulverization preparation method and to investigate the correlation between the concentration of opiates in nail and hair samples from subjects whose urine specimens were positive for morphine. Borate buffer (500 μL; pH 9.2) was added to 20mg of pulverized fingernail, followed by ultrasonication and liquid-liquid extraction. Analytes were analyzed on an Allure PFP propyl column by gradient elution. The mass spectrometer was operated in the positive electrospray ionization mode and multiple reactions monitoring mode. A total of 12 of 18 fingernail samples contained detectable 6-monoacetylmorphine (mean=0.43 ng/mg, range=0.10-1.37 ng/mg), morphine (mean=1.74 ng/mg, range=0.58-3.16 ng/mg) and codeine (range from

  7. [Functional selectivity of opioid receptors ligands].

    Science.gov (United States)

    Audet, Nicolas; Archer-Lahlou, Elodie; Richard-Lalonde, Mélissa; Piñeyro-Filpo, Graciela

    2010-01-01

    Opiates are the most effective analgesics available for the treatment of severe pain. However, their clinical use is restricted by unwanted side effects such as tolerance, physical dependence and respiratory depression. The strategy to develop new opiates with reduced side effects has mainly focused on the study and production of ligands that specifically bind to different opiate receptors subtypes. However, this strategy has not allowed the production of novel therapeutic ligands with a better side effects profile. Thus, other research strategies need to be explored. One which is receiving increasing attention is the possibility of exploiting ligand ability to stabilize different receptor conformations with distinct signalling profiles. This newly described property, termed functional selectivity, provides a potential means of directing the stimulus generated by an activated receptor towards a specific cellular response. Here we summarize evidence supporting the existence of ligand-specific active conformations for two opioid receptors subtypes (delta and mu), and analyze how functional selectivity may contribute in the production of longer lasting, better tolerated opiate analgesics. double dagger.

  8. Recent developments in the study of opioid receptors.

    Science.gov (United States)

    Cox, Brian M

    2013-04-01

    It is now about 40 years since Avram Goldstein proposed the use of the stereoselectivity of opioid receptors to identify these receptors in neural membranes. In 2012, the crystal structures of the four members of the opioid receptor family were reported, providing a structural basis for understanding of critical features affecting the actions of opiate drugs. This minireview summarizes these recent developments in our understanding of opiate receptors. Receptor function is also influenced by amino acid substitutions in the protein sequence. Among opioid receptor genes, one polymorphism is much more frequent in human populations than the many others that have been found, but the functional significance of this single nucleotide polymorphism (SNP) has been unclear. Recent studies have shed new light on how this SNP might influence opioid receptor function. In this minireview, the functional significance of the most prevalent genetic polymorphism among the opioid receptor genes is also considered.

  9. Implicit and Explicit Memory Bias in Opiate Dependent, Abstinent and Normal Individuals

    Directory of Open Access Journals (Sweden)

    Jafar Hasani

    2013-07-01

    Full Text Available Objective: The aim of current research was to assess implicit and explicit memory bias to drug related stimuli in opiate Dependent, abstinent and normal Individuals. Method: Three groups including opiate Dependent, abstinent and normal Individuals (n=25 were selected by available sampling method. After matching on the base of age, education level and type of substance use all participants assessed by recognition task (explicit memory bias and stem completion task (implicit memory bias. Results: The analysis of data showed that opiate dependent and abstinent groups in comparison with normal individual had implicit memory bias, whereas in explicit memory only opiate dependent individuals showed bias. Conclusion: The identification of explicit and implicit memory governing addiction may have practical implications in diagnosis, treatment and prevention of substance abuse.

  10. Opiate Addicted and Non-Addicted Siblings in a Slum Area

    Science.gov (United States)

    Glaser, Daniel; And Others

    1971-01-01

    Compares addicted and non-addicted siblings of families residing in and around a slum block in New York. Data supporting an ideographic relative deprivation-differential anticipation" explanation for current opiate addiction in the U. S. was produced. (JM)

  11. Opiate-induced changes in brain adenosine levels and narcotic drug responses.

    Science.gov (United States)

    Wu, M; Sahbaie, P; Zheng, M; Lobato, R; Boison, D; Clark, J D; Peltz, G

    2013-01-01

    We have very little information about the metabolomic changes that mediate neurobehavioral responses, including addiction. It was possible that opioid-induced metabolomic changes in brain could mediate some of the pharmacodynamic effects of opioids. To investigate this, opiate-induced brain metabolomic responses were profiled using a semi-targeted method in C57BL/6 and 129Sv1 mice, which exhibit extreme differences in their tendency to become opiate dependent. Escalating morphine doses (10-40 mg/kg) administered over a 4-day period selectively induced a twofold decrease (pOpiate-induced changes in brain adenosine levels may explain many important neurobehavioral features associated with opiate addiction and withdrawal.

  12. The Relationship between Motivational Structure, Mental Health and Attitude to Opiate Substances in University Students

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    Ali akbar Soliemanian

    2012-02-01

    Full Text Available Introduction: This study was carried out with the aim of evaluating the relationship between motivational structure, mental health and attitude to opiate substances in a sample of North-Khorasan's university students. Method: In a descriptive cross-sectional study, 400 participants (200 males and 200 females were selected by stratified random sampling of three universities of north khorasan. All participants completed the SCL-90-R, Personal Concerns Inventory and Attitude to Opiate Substances questionnaire. Findings: The results revealed that there was a significant difference between participants with maladaptive motivational structure and adaptive motivational structure on GSI and subscales of SCL-90-R. In addition, the comparison of two groups showed that participants with maladaptive motivational structure had significant more positive attitude to opiate Substances than participants with adaptive motivational structure. Conclusion: There is a significant relationship between motivational structure, mental health and attitude to opiate substances.

  13. Opiate addiction and overdose: experiences, attitudes, and appetite for community naloxone provision.

    LENUS (Irish Health Repository)

    Barry, Tomás

    2017-02-28

    More than 200 opiate overdose deaths occur annually in Ireland. Overdose prevention and management, including naloxone prescription, should be a priority for healthcare services. Naloxone is an effective overdose treatment and is now being considered for wider lay use.

  14. Use of Opiates to Manage Pain in the Seriously and Terminally Ill Patient

    Science.gov (United States)

    ... people with substance abuse and addiction problems have discovered fentanyl patches (a potent opiate), have learned how ... medicines, some heart medicines, steroids, and medicines for diabetes. My sister has bad pain from bone cancer, ...

  15. Opiate addiction and the entanglements of imperialism and patriarchy in Manchukuo, 1932-45.

    Science.gov (United States)

    Smith, Norman

    2005-01-01

    In the Japanese colonial state of Manchukuo, opiate addiction was condemned by officials and critics alike. But the state-sponsored creation of a monopoly, opium laws, and rehabilitation programs failed to reduce rates of addiction. Further, official media condemnation of opiate addiction melded with local Chinese-language literature to stigmatise addiction, casing a negative light over the state's failure to realise its own anti-opiate agenda. Chinese writers were thus transfixed in a complex colonial environment in which they applauded measures to reduce harm to the local population while levelling critiques of Japanese colonial rule. This paper demonstrates how the Chinese-language literature of Manchukuo did not simply parrot official politics. It also delegitimised Japanese rule through opiate narratives that are gendered, consistently negative, and more critical of the state than might be expected in a colonial literature.

  16. Receipt of Prescribed Controlled Substances by Adolescents and Young Adults Prior to Presenting for Opiate Dependence Treatment

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    Steven C. Matson

    2013-01-01

    Full Text Available Purpose. The objective of this study was to document the number of controlled substance prescriptions filled by adolescents and young adult patients in the 2 years prior to presentation for opiate dependence treatment. Methods. Opiate-dependent youth ( presenting to our Medication-Assisted Treatment for Addiction program from January 1, 2008 to June 30, 2010 were identified via electronic medical record. Subjects were further classified based on their opiate use as dependent to heroin-only, prescription (Rx opiate-only, or combined heroin + Rx opiate only. The Ohio Automated Rx Reporting System (OARRS was used to identify each subject's controlled substance prescription history. Negative binomial regression was used to examine the relationships between patient characteristics and the total number of prescriptions filled. Results. Twenty-five percent of subjects had filled ≥6 prescriptions, and 15% had filled ≥11 prescriptions. The mean number of prescriptions filled was 5 (range: 0–59. Thirteen percent had filled ≥6 opiate/narcotic prescriptions, and 8% had filled ≥11 prescriptions. Conclusions. A subset of opiate-dependent youth had filled multiple opiate/narcotic prescriptions providing some evidence that physician-provided prescriptions may be a source of opiate abuse or diversion for a minority of opiate-dependent adolescents and young adults.

  17. Cocaine- and opiate-related fatal overdose in New York City, 1990-2000.

    Science.gov (United States)

    Bernstein, Kyle T; Bucciarelli, Angela; Piper, Tinka Markham; Gross, Charles; Tardiff, Ken; Galea, Sandro

    2007-03-09

    In New York City (NYC), the annual mortality rate is higher for accidental drug overdoses than for homicides; cocaine and opiates are the drugs most frequently associated with drug overdose deaths. We assessed trends and correlates of cocaine- and opiate-related overdose deaths in NYC during 1990-2000. Data were collected from the NYC Office of the Chief Medical Examiner (OCME) on all fatal drug overdoses involving cocaine and/or opiates that occurred between 1990-2000 (n = 8,774) and classified into three mutually exclusive groups (cocaine only; opiates-only; cocaine and opiates). Risk factors for accidental overdose were examined in the three groups and compared using multinomial logistic regression. Overall, among decedents ages 15-64, 2,392 (27.3%) were attributed to cocaine only and 2,825 (32.2%) were attributed to opiates-only. During the interval studied, the percentage of drug overdose deaths attributed to cocaine only fell from 29.2% to 23.6% while the percentage of overdose deaths attributed to opiates-only rose from 30.6% to 40.1%. Compared to New Yorkers who fatally overdosed from opiates-only, fatal overdose attributed to cocaine-only was associated with being male (OR = 0.71, 95% CI 0.62-0.82), Black (OR = 4.73, 95% CI 4.08-5.49) or Hispanic (OR = 1.51, 95% CI 1.29-1.76), an overdose outside of a residence or building (OR = 1.34, 95% CI 1.06-1.68), having alcohol detected at autopsy (OR = 0.50, 95% CI 0.44-0.56) and older age (55-64) (OR = 2.53 95% CI 1.70-3.75)). As interventions to prevent fatal overdose become more targeted and drug specific, understanding the different populations at risk for different drug-related overdoses will become more critical.

  18. Characteristics and Outcomes of Young Adult Opiate Users Receiving Residential Substance Abuse Treatment.

    Science.gov (United States)

    Morse, Siobhan; MacMaster, Samuel

    2015-01-01

    Opiate use patterns, user characteristics, and treatment response among young adults are of interest due to current high use prevalence and historical low levels of treatment engagement relative to older populations. Prior research in this population suggests that overall, young adults present at treatment with different issues. In this study the authors investigated potential differences between young adult (18-25 years of age) and older adult (26 and older) opiate users and the impact of differences relative to treatment motivation, length and outcomes. Data for this study was drawn from 760 individuals who entered voluntary, private, residential treatment. Study measures included the Addiction Severity Index (ASI), the Treatment Service Review (TSR), and University of Rhode Island Change Assessment (URICA). Interviews were conducted at program intake and 6-month post-discharge. Results indicate that older adults with a history of opiate use present at treatment with higher levels of severity for alcohol, medical, and psychological problems and young adults present at treatment with greater drug use and more legal issues. Significant improvement for both groups was noted at 6 months post treatment; there were also fewer differences between the two age groups of opiate users. Results suggest different strategies within treatment programs may provide benefit in targeting the disparate needs of younger opiate users. Overall, however, results suggest that individualized treatment within a standard, abstinence-based, residential treatment model can be effective across opiate users at different ages and with different issues, levels of severity, and impairment at intake.

  19. The Role of Family Atmosphere in the Relapse Behavior of Iranian Opiate Users: a Qualitative Study

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    Hamid Peyrovi

    2015-09-01

    Full Text Available Introduction Many Iranian opiate users live with family members and family atmosphere can be influential on reducing such social behaviors of opiate users as substance use and relapses. This paper reports the impact of family atmosphere on relapse behavior as a part of the findings of a larger study that explored the relapse process among Iranian opiate users. Methods: In this qualitative research, we selected 17 participants (5 women and 12 men. The questions were been asked through semi-structured interviews. The researchers analyzed the verbatim transcripts using content analysis method. Results: "Family atmosphere" with three sub-themes (family and tribes' interaction, family challenges and family structure was been found as determinants of relapse behavior. The quality of the family atmosphere could be in harmony with or against the willingness or motivation of the opiate user towards the relapse. Conclusion Health care providers should reinforce involvement of the family members in the treatment and rehabilitation of opiate users. The opiate user's family and even relatives may benefit from learning how to manage their own feelings and attitude towards the client and being supportive during interactions.

  20. Comparison of temperament and character personality traits in opiate and stimulant addicts

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    Fatemeh Sadeghi Pouya

    2016-11-01

    Full Text Available Background: Phenomenon of addiction as one of the social problems has a high prevalence, especially among youth. The aim of the present study was to compare personality traits based on the temperament and character inventory in opiate and stimulant addicts in Tehran.  Methods: In the present quasi-experimental study, 60 male addicts (30 opiate and 30 stimulant addicts who referred to addiction treatment centers in the suburbs of Tehran were selected through convenience sampling method and were studied using Temperament and Character Inventory (TCI. The participants were sorted according to their age and education.    Results: There was a significant difference between the two groups with regard to harm avoidance, reward dependence, cooperativeness, and self-transcendence traits. Thus, opiate addicts had higher levels of harm avoidance, reward dependence, and cooperativeness, and stimulant addicts had higher levels of self-transcendence. The significance level was set at P<0.01.  Conclusion: The obtained results showed that there was a significant difference between opiate and stimulant addicts. Opiate addicts gained higher scores, compared with stimulant addicts, in Temperament and Character Inventory variables. The obtained results also showed that stimulant addicts were suffering from more severe disorders than opiate addicts. Based on the means of the values of the TCI, personality traits reflecting personality disorders are detectable and predictable in substance abusers. This new understanding is important in the prevention and treatment of addiction.

  1. Outcomes of coronary artery bypass grafting in patients with a history of opiate use.

    Science.gov (United States)

    Safaei, Nasser

    2008-11-15

    This study aimed at evaluating the outcome of CABG in patients with a history of opiate use. Two hundred male patients, underwent CABG surgery, were evaluated and followed up for 6 months. The patients classified as Group P (with Previous history of opiate use) and Group N (with No history of opiate use). The characteristics and 6-month outcomes were compared between the two groups. Patients in group P further categorized into two subgroups of active and non-active abusers. Two hundred male-patients enrolled in the study, 23 (11.5%) patients had a history of opiate abuse. Nine (4.5%) patients were past users and 14 (7%) cases were current users. There were no significant differences regarding the age, history of hypertension, smoking, ejection fraction before and 6 months after CABG, duration of hospital stay, complications of surgery and function class (p<0.05). The level of patients obeys from physician's medical, nutritional and activity recommendations after CABG was significantly lower for current opiate users. Also, the need for readmission after CABG due to cardiac complications was independently higher in current opiate users. Carrying out the educational programs to correct the misconception about the beneficial effects of illicit drugs on cardio-vascular disease makes sense.

  2. Illicit tranquilliser use and dependence among female opiate users.

    Science.gov (United States)

    Gilchrist, Gail; Atkinson, Jacqueline; Gruer, Laurence

    2006-09-01

    This study determined the predictors of 12-month dependence on illicit tranquillisers among female opiate users attending three services in Glasgow, Scotland, UK. Twelve-month drug dependence was measured using the Diagnostic Interview Schedule. The Revised Clinical Interview Schedule (CIS-R) measured current neurotic symptoms. 60% (159/266) had used illicit tranquillisers in the past 30 days, and 50% (132/266) met criteria for 12-month dependence on illicit tranquillisers. Polydrug use, injecting drug use, childhood and adulthood abuse, adverse life experiences and current and previous mental health problems were associated with 12-month dependence on illicit tranquillisers. Using multiple logistic regression, polydrug use in last 30 days (OR 3.2, 95% CI 1.5 - 7.0), history of deliberate self-harm (OR 2.5, 95% CI 1.4 - 4.4), history of injecting drug use (OR 2.5, 1.2 - 5.2) and likely to need treatment for current neurotic symptoms (CIS-R > or = 18) (OR 2.4, 95% CI 1.3 - 4.4) predicted 12-month dependence on illicit tranquillisers. Drug users in general and female drug users in particular who are using illicit tranquillisers are also particularly likely to have psychiatric symptoms requiring treatment. Mental health problems should be assessed and monitored among this client group and counselling and psychosocial support should be provided when indicated.

  3. Characteristics of opiate users leaving detoxification treatment against medical advice.

    Science.gov (United States)

    Kenne, Deric R; Boros, Alec P; Fischbein, Rebecca L

    2010-07-01

    Substance-dependent patients leaving against medical advice (AMA) pose a unique challenge to detoxification programs. Most notably, AMA patients fail to access residential or outpatient treatment needed after detoxification and often return to detoxification treatment multiple times which has deleterious results for the patient and is taxing to the healthcare system. Using retrospective data from 89 daily opiate-using detoxification patients completing detoxification and 95 patients leaving AMA, we sought to identify patient characteristics useful in predicting AMA discharges from detoxification. Bivariate analyses indicated that AMA patients reported drug use did not impair their health, were injection drug users, younger and had fewer previous treatment admissions. Binomial logistic regression indicated that AMA patients were more likely to be unemployed and report that drug use did not impair their health. Patients completing detoxification were less likely to be injection drug users and less likely to be self-referred to treatment. Identifying patients at risk of leaving AMA provides an opportunity for clinicians to intervene in an effort to increase treatment engagement for these patients.

  4. Heroin-assisted treatment as a response to the public health problem of opiate dependence.

    Science.gov (United States)

    Fischer, Benedikt; Rehm, Jürgen; Kirst, Maritt; Casas, Miguel; Hall, Wayne; Krausz, Michael; Metrebian, Nicky; Reggers, Jean; Uchtenhagen, Ambros; van den Brink, Wim; van Ree, Jan M

    2002-09-01

    Injection drug use (involving the injection of illicit opiates) poses serious public health problems in many countries. Research has indicated that injection drug users are at higher risk for morbidity in the form of HIV/AIDS and Hepatitis B and C, and drug-related mortality, as well as increased criminal activity. Methadone maintenance treatment is the most prominent form of pharmacotherapy treatment for illicit opiate dependence in several countries, and its application varies internationally with respect to treatment regulations and delivery modes. In order to effectively treat those patients who have previously been resistant to methadone maintenance treatment, several countries have been studying and/or considering heroin-assisted treatment as a complementary form of opiate pharmacotherapy treatment. This paper provides an overview of the prevalence of injection drug use and the opiate dependence problem internationally, the current opiate dependence treatment landscape in several countries, and the status of ongoing or planned heroin-assisted treatment trials in Australia, Canada and certain European countries.

  5. Executive functions and risky decision-making in patients with opiate dependence.

    Science.gov (United States)

    Brand, Matthias; Roth-Bauer, Martina; Driessen, Martin; Markowitsch, Hans J

    2008-09-01

    Recent evidence suggests that individuals with opiate dependence may have cognitive dysfunctions particularly within the spectrum of executive functioning and emotional processing. Such dysfunctions can also compromise daily decisions associated with risk-taking behaviors. However, it remains unclear whether patients addicted to opiates show impaired decision-making on gambling tasks that specify explicit rules for rewards and punishments and provide information about probabilities associated with different long-term outcomes. In this study, we examined 18 individuals with opiate dependence and 18 healthy comparison subjects, matched for age, gender, and education with the Game of Dice Task (GDT). The GDT is a gambling task with explicit rules for gains and losses and fix winning probabilities. In addition, all subjects completed a neuropsychological test battery that primarily focused on executive functions and a personality questionnaire. On the GDT, patients chose the risky alternatives more frequently than the control group. Patients' GDT performance was related to executive functioning but not to other neuropsychological constructs, personality or dependence specific variables with one exception that is the number of days of abstinence. Thus, patients with opiate dependence demonstrate abnormalities in decision-making that might be neuropsychologically associated with dysfunctional behavior in patients' daily lives. Decision-making and other neuropsychological functioning should be considered in the treatment of opiate dependence.

  6. Decision-making ability in current and past users of opiates: A meta-analysis.

    Science.gov (United States)

    Biernacki, Kathryn; McLennan, Skye N; Terrett, Gill; Labuschagne, Izelle; Rendell, Peter G

    2016-12-01

    Opiate use is associated with deficits in decision-making. However, the impact of abstinence and co-morbid factors, like head injury and poly-substance abuse, on this ability, is currently unclear. This meta-analysis aimed to assess 1) the magnitude of decision-making deficits in opiate users; 2) whether co-morbid factors moderate the severity of these deficits; 3) whether ex-opiate users demonstrate smaller decision-making deficits than current users; and 4) whether the length of abstinence is related to the magnitude of decision-making deficits. We analysed 22 studies that compared the performance of current and ex-opiate users to healthy controls on decision-making measures such as the Iowa Gambling Task. Current users demonstrated a moderately strong impairment in decision-making relative to controls, which was not significantly moderated by co-morbid factors. The magnitude of the impairment did not significantly differ between studies assessing current or ex-users, and this impairment was not related to length of abstinence. Thus, it appears that opiate users have relatively severe decision-making deficits that persist at least 1.5 years after cessation of use.

  7. [Spinal opiates in obstetrics. Theoretical aspects and criteria for practical use].

    Science.gov (United States)

    Miranda, A

    1995-11-01

    Spinal opiates were introduced for use in obstetrics during the 1980's. The possibility of achieving analgesic effects with small doses, without motor and/or vegetative involvement, initially aroused a great deal of enthusiasm. After extensive experience using these drugs, however, it seems they only partially live up to these great expectations. Savings on dose seem to be attained only with morphine and the efficacy of spinal opiates used as the only agents against pain during childbirth is limited. Intradural administration is often accompanied by vegetative involvement, and the reduction in motor blockade generally does not have substantial effect on the progression of labor. On the other hand, it is important to underline the advantages of combining opiates with local anesthesia: both doses are reduced, quality of analgesia is greater, as is maternal satisfaction, and fetal/neonatal repercussions are scarce. Finally, in certain cases, opiates may constitute a valid alternative for local anesthesia, especially if delivery is intradural. The use of spinal opiates is certainly an important qualitative advance, though not a definitive one, in obstetrics.

  8. Opioid receptor desensitization: mechanisms and its link to tolerance

    Directory of Open Access Journals (Sweden)

    Stéphane eAllouche

    2014-12-01

    Full Text Available Opioid receptors are part of the class A of G-protein coupled receptors and the target of the opiates, the most powerful analgesic molecules used in clinic. During a protracted use, a tolerance to analgesic effect develops resulting in a reduction of the effectiveness. So understanding mechanisms of tolerance is a great challenge and may help to find new strategies to tackle this side effect. This review will summarize receptor-related mechanisms that could underlie tolerance especially receptor desensitization. We will focus on the latest data obtained on molecular mechanisms involved in opioid receptor desensitization: phosphorylation, receptor uncoupling, internalization and post-endocytic fate of the receptor.

  9. Opiate addiction therapies and HIV-1 Tat: interactive effects on glial [Ca²⁺]i, oxyradical and neuroinflammatory chemokine production and correlative neurotoxicity.

    Science.gov (United States)

    Fitting, Sylvia; Zou, Shiping; El-Hage, Nazira; Suzuki, Masami; Paris, Jason J; Schier, Christina J; Rodríguez, José W; Rodriguez, Myosotys; Knapp, Pamela E; Hauser, Kurt F

    2014-01-01

    Few preclinical studies have compared the relative therapeutic efficacy of medications used to treat opiate addiction in relation to neuroAIDS. Here we compare the ability of methadone and buprenorphine, and the prototypic opiate morphine, to potentiate the neurotoxic and proinflammatory ([Ca²⁺]i, ROS, H₂O₂, chemokines) effects of HIV-1 Tat in neuronal and/or mixed-glial co-cultures. Repeated observations of neurons during 48 h exposure to combinations of Tat, equimolar concentrations (500 nM) of morphine, methadone, or buprenorphine exacerbated neurotoxicity significantly above levels seen with Tat alone. Buprenorphine alone displayed marked neurotoxicity at 500 nM, prompting additional studies of its neurotoxic effects at 5 nM and 50 nM concentrations ± Tat. In combination with Tat, buprenorphine displayed paradoxical, concentration-dependent, neurotoxic and neuroprotective actions. Buprenorphine neurotoxicity coincided with marked elevations in [Ca²⁺]i, but not increases in glial ROS or chemokine release. Tat by itself elevated the production of CCL5/RANTES, CCL4/MIP-1β, and CCL2/MCP-1. Methadone and buprenorphine alone had no effect, but methadone interacted with Tat to further increase production of CCL5/RANTES. In combination with Tat, all drugs significantly increased glial [Ca²⁺]i, but ROS was only significantly increased by co-exposure with morphine. Taken together, the increases in glial [Ca²⁺]i, ROS, and neuroinflammatory chemokines were not especially accurate predictors of neurotoxicity. Despite similarities, opiates displayed differences in their neurotoxic and neuroinflammatory interactions with Tat. Buprenorphine, in particular, was partially neuroprotective at a low concentration, which may result from its unique pharmacological profile at multiple opioid receptors. Overall, the results reveal differences among addiction medications that may impact neuroAIDS.

  10. KPNA3 Variation Is Associated with Schizophrenia, Major Depression, Opiate Dependence and Alcohol Dependence

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    Charles P. Morris

    2012-01-01

    Full Text Available KPNA3 is a gene that has been linked to schizophrenia susceptibility. In this study we investigated the possible association between KPNA3 variation and schizophrenia. To investigate a wider role of KPNA3 across psychiatric disorders we also analysed major depression, PTSD, nicotine dependent, alcohol dependent and opiate dependent cohorts. Using a haplotype block-based gene-tagging approach we genotyped six KPNA3 single nucleotide polymorphisms (SNPs in 157 schizophrenia patients, 121 post-traumatic stress disorder patients, 120 opiate dependent patients, 231 alcohol dependent patients, 147 nicotine dependent patients and 266 major depression patients. One SNP rs2273816 was found to be significantly associated with schizophrenia, opiate dependence and alcohol dependence at the genotype and allele level. Major depression was also associated with rs2273816 but only at the allele level. Our study suggests that KPNA3 may contribute to the genetic susceptibility to schizophrenia as well as other psychiatric disorders.

  11. Auditory target processing in methadone substituted opiate addicts: The effect of nicotine in controls

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    Zerbin Dieter

    2007-11-01

    Full Text Available Abstract Background The P300 component of the auditory evoked potential is an indicator of attention dependent target processing. Only a few studies have assessed cognitive function in substituted opiate addicts by means of evoked potential recordings. In addition, P300 data suggest that chronic nicotine use reduces P300 amplitudes. While nicotine and opiate effects combine in addicted subjects, here we investigated the P300 component of the auditory event related potential in methadone substituted opiate addicts with and without concomitant non-opioid drug use in comparison to a group of control subjects with and without nicotine consumption. Methods We assessed 47 opiate addicted out-patients under current methadone substitution and 65 control subjects matched for age and gender in an 2-stimulus auditory oddball paradigm. Patients were grouped for those with and without additional non-opioid drug use and controls were grouped for current nicotine use. P300 amplitude and latency data were analyzed at electrodes Fz, Cz and Pz. Results Patients and controls did not differ with regard to P300 amplitudes and latencies when whole groups were compared. Subgroup analyses revealed significantly reduced P300 amplitudes in controls with nicotine use when compared to those without. P300 amplitudes of methadone substituted opiate addicts were in between the two control groups and did not differ with regard to additional non-opioid use. Controls with nicotine had lower P300 amplitudes when compared to patients with concomitant non-opioid drugs. No P300 latency effects were found. Conclusion Attention dependent target processing as indexed by the P300 component amplitudes and latencies is not reduced in methadone substituted opiate addicts when compared to controls. The effect of nicotine on P300 amplitudes in healthy subjects exceeds the effects of long term opioid addiction under methadone substitution.

  12. Parámetros hematológicos en pacientes opiaceodependientes Haemotologic parameters in opiate addicts

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    C. del M. Verde Méndez

    2003-12-01

    Full Text Available Se determinaron los niveles de hemoglobina, hematocrito, hematíes, recuento de leucocitos, índices relacionados con la serie roja (VCM, HCM, CHCM, IDE, VPM, velocidad de sedimentación, hierro, parámetros relacionados con la captación y transporte de hierro (transferrina, ferritina, capacidad de fijación de hierro, índice de saturación de transferrina y plaquetas en muestras sanguíneas de opiaceodependientes y se compararon los resultados con los obtenidos en un grupo control. En general, para ambos sexos los niveles de hemoglobina, hematocrito, hierro y plaquetas fueron similares en el grupo control y en los opiaceodependientes. Las mujeres opiaceodependientes presentaron un recuento de hematíes y leucocitos superior e inferior respectivamente, que los correspondientes valores del grupo control. Se observó que en el total de pacientes opiaceodependientes, así como en los subgrupos de mujeres y hombres, los índices relacionados con la serie roja fueron superiores con respecto al grupo control. Los niveles de ferritina en opiaceodependientes varones fueron superiores a los encontrados en los controles, mientras que en las mujeres ocurrió lo contrario. Se observó que los hombres y mujeres opiaceodependientes incluidos en el programa de mantenimiento con metadona (PMM presentaron valores de hemoglobina, hematocrito, hematíes y recuento de leucocitos similares a los no incluidos, exceptuando los heroinómanos varones incluidos en el PMM que mostraron valores inferiores de hematocrito.Levels of haemoglobin, haematocrit, number of red cells and leukocytes, haematological index (MCV, MCH, MCHC, DEI, MPV, sedimentation rate, iron, parameter related to accumulation and transport of iron (transferrin, ferritin, iron binding capability, transferring saturation index and platelets were determined in blood samples of opiate addicts and they were compared with these results obtained in a control group. For both sexes, the levels of haemoglobin

  13. Cocaine- and opiate-related fatal overdose in New York City, 1990–2000

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    Tardiff Ken

    2007-03-01

    Full Text Available Abstract Background In New York City (NYC, the annual mortality rate is higher for accidental drug overdoses than for homicides; cocaine and opiates are the drugs most frequently associated with drug overdose deaths. We assessed trends and correlates of cocaine- and opiate-related overdose deaths in NYC during 1990–2000. Methods Data were collected from the NYC Office of the Chief Medical Examiner (OCME on all fatal drug overdoses involving cocaine and/or opiates that occurred between 1990–2000 (n = 8,774 and classified into three mutually exclusive groups (cocaine only; opiates-only; cocaine and opiates. Risk factors for accidental overdose were examined in the three groups and compared using multinomial logistic regression. Results Overall, among decedents ages 15–64, 2,392 (27.3% were attributed to cocaine only and 2,825 (32.2% were attributed to opiates-only. During the interval studied, the percentage of drug overdose deaths attributed to cocaine only fell from 29.2% to 23.6% while the percentage of overdose deaths attributed to opiates-only rose from 30.6% to 40.1%. Compared to New Yorkers who fatally overdosed from opiates-only, fatal overdose attributed to cocaine-only was associated with being male (OR = 0.71, 95% CI 0.62–0.82, Black (OR = 4.73, 95% CI 4.08–5.49 or Hispanic (OR = 1.51, 95% CI 1.29–1.76, an overdose outside of a residence or building (OR = 1.34, 95% CI 1.06–1.68, having alcohol detected at autopsy (OR = 0.50, 95% CI 0.44–0.56 and older age (55–64 (OR = 2.53 95% CI 1.70–3.75. Conclusion As interventions to prevent fatal overdose become more targeted and drug specific, understanding the different populations at risk for different drug-related overdoses will become more critical.

  14. Simultaneous quantification of cocaine, amphetamines, opiates and cannabinoids in vitreous humor.

    Science.gov (United States)

    Peres, Mariana Dadalto; Pelição, Fabrício Souza; Caleffi, Bruno; De Martinis, Bruno Spinosa

    2014-01-01

    A GC-MS method for simultaneous analysis of cocaine (COC), amphetamines (AMPs), opiates, cannabinoids and their metabolites in vitreous humor (VH) was developed and fully validated. VH samples were extracted using solid phase extraction and injected into the GC-MS, using a selected ion monitoring mode. Linearity ranged from 10 to 1000 ng/mL; the exception was anhydroecgonine methyl ester (AEME), for which linearity ranged from 10 to 750 ng/mL. Inter-assay imprecision lay from 1.2 to 10.0%, intra-assay imprecision was opiates and their metabolites.

  15. receptores

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    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  16. Association between DRD2, 5-HTTLPR, and ALDH2 genes and specific personality traits in alcohol- and opiate-dependent patients.

    Science.gov (United States)

    Wang, Tzu-Yun; Lee, Sheng-Yu; Chen, Shiou-Lan; Huang, San-Yuan; Chang, Yun-Hsuan; Tzeng, Nian-Sheng; Wang, Chen-Lin; Hui Lee, I; Yeh, Tzung Lieh; Yang, Yen Kuang; Lu, Ru-Band

    2013-08-01

    The vulnerability of developing addictions is associated with genetic factors and personality traits. The predisposing genetic variants and personality traits may be common to all addictions or specific to a particular class of addiction. To investigate the relationship between genetic variances, personality traits, and their interactions in addiction are important. We recruited 175 opiate-dependent patients, 102 alcohol-dependent patients, and 111 healthy controls. All participants were diagnosed using DSM-IV criteria and assessed with Tridimensional Personality Questionnaire (TPQ). The dopamine D2 receptor (DRD2), 5-HTT-linked promoter region (5-HTTLPR), and aldehyde dehydrogenase 2 (ALDH2) genes were genotyped using PCR. The genotype frequency of the 5-HTTLPR and ALDH2 was significantly different between the patients and controls (P=0.013, Ptraits, whereas addicts with ALDH2 *1/*2 or *2/*2 and low-functional group of DRD2 and 5-HTTLPR genes have higher NS traits. We concluded that addicts, both alcohol- and opiate-dependent patients, have common genetic variants in DRD2 and 5-HTTLPR but specific for ALDH2. Higher NS and HA traits were found in both patient groups with the interaction with DRD2, 5-HTTLPR, and ALDH2 genes. The ALDH2 gene variants had different effect in the NS and HA dimension while the DRD2 and 5-HTTLPR genes did not.

  17. Differentiating Violent and Nonviolent Opiate-Addicted Reformatory Inmates with the MMPI.

    Science.gov (United States)

    Chick, Garry E.; And Others

    1984-01-01

    Discriminated among four groups of male opiate-addicted reformatory inmates (N=193) according to degree of criminal violence using the Minnesota Multiphasic Personality Inventory (MMPI). Results showed that discriminant analysis was moderately successful for classifying Bodily Violent and Nonbodily Violent groups on the basis of their MMPI scores.…

  18. Predicting Sobriety from the Employment Status of Dually Diagnosed Clients Who Are Opiate Dependent

    Science.gov (United States)

    Scorzelli, James F.

    2007-01-01

    The purpose of this study was to determine the relationship between Minnesota Multiphasic Personality Inventory-2 (E. S. Neukrug & R. C. Fawcett, 2006) profiles and employment status for clients who are opiate dependent. A discriminant function analysis indicated that employment was a predictor in maintaining sobriety after 6 months. (Contains 4…

  19. Psychometric Evaluation of the Life Orientation Test-Revised in Treated Opiate Dependent Individuals

    Science.gov (United States)

    Hirsch, Jameson K.; Britton, Peter C.; Conner, Kenneth R.

    2010-01-01

    We examined internal consistency and test-retest reliability of a measure of dispositional optimism, the Life Orientation Test-Revised, in 121 opiate-dependent patients seeking methadone treatment. Internal consistency was adequate at baseline (alpha = 0.69) and follow-up (alpha = 0.72). Low socioeconomic status and being on disability were…

  20. Relationships Between Using Other Substances and Socio-Demographic Characteristics in Opiate Dependents

    Directory of Open Access Journals (Sweden)

    Melike Nebioglu,Hacer Yalniz

    2013-02-01

    Full Text Available Objective: We aimed to determine the variables that can be a risk factor for addiction like age, gender, education level, school cession, first using age, substance use period, frequency and using other addictive substances among people who have a diagnosis of opiate addiction. Methods: This is a descriptive and cross-sectional study in AMBAUM ( Akdeniz University Alcohol and Substance Dependence Research and Practice Center between February 1,2010- April30, 2010. 84 inpatient and outpatient patients (60 men, 24 women between age 14-37, who have a diagnosis of opiate addiction according to DSM IV-TR diagnostic criteria recruited in this study. All participating patients completed a standard questionaire and sociodemographic data form face to face. The results were analyzed with chi-squared test by using SPSS 16 statistics program. Results: In our patients nicotin addiction prevalance is 100%, alcohol using prevalance is 91.7%, cannabis using prevalance 86.9%, ecstasy using prevalance 54.8%, cocain using prevalance 48.8%, polysubstance using prevalance 47.6%, hallucinogen using prevalance 27.4%, addictive medical drug using prevalance 17.9%. Conclusions: This epidemiological study guide us in the monitoring and evalution of the opiate use and prevalance of other substance use with opiate addiction. Keywords: Prevalence, heroin, polysubstance dependence. [TAF Prev Med Bull 2013; 12(1.000: 35-42

  1. Psychometric evaluation of the Dutch version of the Subjective Opiate Withdrawal Scale (SOWS)

    NARCIS (Netherlands)

    Dijkstra, B.A.G.; Krabbe, P.F.M.; Riezebos, T.G.M.; Staak, C.P.F. van der; Jong, C.A.J. de

    2007-01-01

    AIM: To evaluate the psychometric properties of the Dutch version of the 16-item Subjective Opiate Withdrawal Scale (SOWS). The SOWS measures withdrawal symptoms at the time of assessment. METHODS: The Dutch SOWS was repeatedly administered to a sample of 272 opioid-dependent inpatients of four addi

  2. Prenatal care, pregnancy outcomes, and postpartum birth control plans among pregnant women with opiate addictions.

    Science.gov (United States)

    Parlier, Anna Beth; Fagan, Blake; Ramage, Melinda; Galvin, Shelley

    2014-11-01

    To describe how effectively we provided adequate prenatal care and postpartum contraception to prevent repeat, unintended pregnancies to women using opiates or medication maintenance therapy (MMT) during pregnancy. We conducted a retrospective chart review of 94 women using opiates or MMT during 96 pregnancies while receiving prenatal care in the regional high-risk maternity care clinic between July 2010 and June 2012. We examined prenatal care usage, birth outcomes, and postpartum contraception using χ(2), Kruskal-Wallis, and binary logistic regression modeling. Patients were predominately white (93.6%), multiparous (75.5%), and in their 20s; 71 (74%) used MMT and 25 (26%) used prescribed or illicit opiates. Fewer than half (44% [46.2%]) received any documented prenatal counseling about postpartum contraception. Sixteen (17%) babies were premature. Sixty-four (66.7%) infants were diagnosed as having neonatal abstinence syndrome (NAS). Only 42 (43.8%) women attended their postpartum visits. Overall, 60 (62.5%) women received postpartum contraception. The only significant predictors of postpartum contraception use were preterm birth and postpartum appointment attendance. Alternative strategies for providing postpartum care should be explored because women using opiates or MMT during pregnancy are significantly more likely to use postpartum contraception if they attend their postpartum appointments.

  3. Extinction of morphine-dependent conditioned behavior is associated with increased phosphorylation of the GluR1 subunit of AMPA receptors at hippocampal synapses

    OpenAIRE

    Billa, Sophie K.; Sinha, Namita; Rudrabhatla, Sri Rajyalakshmi; Morón, Jose A.

    2008-01-01

    In abstinent opiate addicts, relapse can be triggered by exposure to environmental cues associated with drug use; thus, the disruption of these learned associations may be an effective approach for reducing relapse. Interestingly, glutamatergic systems are thought to be involved in opiate-induced behavioral plasticity. In this study, changes in expression and phosphorylation levels of AMPA glutamate receptor subunits (GluR1, GluR2) in the hippocampus were investigated in rats showing a condit...

  4. Racial Differences in Opiate Administration for Pain Relief at an Academic Emergency Department

    Directory of Open Access Journals (Sweden)

    Dickason, R. Myles

    2015-05-01

    Full Text Available Introduction: The decision to treat pain in the emergency department (ED is a complex, idiosyncratic process. Prior studies have shown that EDs undertreat pain. Several studies demonstrate an association between analgesia administration and race. This is the first Midwest single institution study to address the question of race and analgesia, in addition to examining the effects of both patient and physician characteristics on race-based disparities in analgesia administration. Methods: This was a retrospective chart review of patients presenting to an urban academic ED with an isolated diagnosis of back pain, migraine, or long bone fracture (LBF from January 1, 2007 to December 31, 2011. Demographic and medication administration information was collected from patient charts by trained data collectors blinded to the hypothesis of the study. The primary outcome was the proportion of African-Americans who received analgesia and opiates, as compared to Caucasians, using Pearson’s chi-squared test. We developed a multiple logistic regression model to identify which physician and patient characteristics correlated with increased opiate administration. Results: Of the 2,461 patients meeting inclusion criteria, 57% were African-American and 30% Caucasian (n=2136. There was no statistically significant racial difference in the administration of any analgesia (back pain: 86% vs. 86%, p=0.81; migraine: 83% vs. 73%, p=0.09; LBF: 94% vs. 90%, p=0.17, or in opiate administration for migraine or LBF. African-Americans who presented with back pain were less likely to receive an opiate than Caucasians (50% vs. 72%, p<0.001. Secondary outcomes showed that higher acuity, older age, physician training in emergency medicine, and male physicians were positively associated with opiate administration. Neither race nor gender patient-physician congruency correlated with opiate administration. Conclusion: No race-based disparity in overall analgesia administration was

  5. Behavioral expression of opiate withdrawal is altered after prefrontocortical dopamine depletion in rats: monoaminergic correlates.

    Science.gov (United States)

    Espejo, E F; Serrano, M I; Caillé, S; Stinus, L

    2001-08-01

    The objective of this study was to establish the effects of prefrontocortical dopamine depletion on opiate withdrawal and prefrontocortical neurochemical changes elicited by morphine dependence and withdrawal. The dopaminergic content was also measured in the nucleus accumbens during withdrawal, in order to detect reactive changes induced by prefrontocortical lesion. Withdrawal was induced by naloxone in morphine-dependent rats. Monoamine levels were analyzed post-mortem by high performance liquid cromatography. The results showed that chronic morphine dependence did not modify basal levels of monoamines in sham rats, revealing neuroadaptation of prefrontocortical dopamine, noradrenaline and serotonin systems to chronic morphine. The neuroadaptive phenomenon remained after prefrontocortical lesion (> 79% dopamine depletion). On the other hand, a strong increase of dopamine, noradrenaline, and serotonin contents in the medial prefrontal cortex of sham rats was detected during opiate withdrawal. However, in lesioned rats, the increase of prefrontocortical dopamine and serotonin content, but not that of noradrenaline, was much lower. In the nucleus accumbens, prefrontocortical lesion reactively enhanced the dopaminergic tone and, although opiate withdrawal reduced dopaminergic activity in both sham and lesioned rats, this reduction was less intense in the latter group. At a behavioral level, some symptoms of physical opiate withdrawal were exacerbated in lesioned rats (writhing, mastication, teeth-chattering, global score) and exploration was reduced. The findings hence indicate that: (i) prefrontocortical monoaminergic changes play a role in the behavioral expression of opiate withdrawal; (ii) the severity of some withdrawal signs are related to the dopaminergic and serotonergic tone of the medial prefrontal cortex rather than to the noradrenergic one, and (iii) an inverse relationship between mesocortical and mesolimbic dopaminergic systems exists.

  6. Morphine and Codeine Concentrations in Human Urine following Controlled Poppy Seeds Administration of Known Opiate Content

    Science.gov (United States)

    Smith, Michael L.; Nichols, Daniel C.; Underwood, Paula; Fuller, Zachary; Moser, Matthew A.; LoDico, Charles; Gorelick, David A.; Newmeyer, Matthew N.; Concheiro, Marta; Huestis, Marilyn A.

    2014-01-01

    Opiates are an important component for drug testing due to their high abuse potential. Proper urine opiate interpretation includes ruling out poppy seed ingestion; however, detailed elimination studies after controlled poppy seed administration with known morphine and codeine doses are not available. Therefore, we investigated urine opiate pharmacokinetics after controlled oral administration of uncooked poppy seeds with known morphine and codeine content. Participants were administered two 45g oral poppy seed doses 8h apart, each containing 15.7mg morphine and 3mg codeine. Urine was collected ad libitum up to 32h after the first dose. Specimens were analyzed with the Roche Opiates II immunoassay at 2,000 and 300μg/L cutoffs, and the ThermoFisher CEDIA® Heroin Metabolite (6-acetylmorphine, 6AM) and Lin-Zhi 6AM immunoassays with 10μg/L cutoffs to determine if poppy seed ingestion could produce positive results in these heroin marker assays. In addition, all specimens were quantified for morphine and codeine by GC/MS. Participants (N=22) provided 391 urine specimens over 32h following dosing; 26.6% and 83.4% were positive for morphine at 2,000 and 300μg/L GC/MS cutoffs, respectively. For the 19 subjects who completed the study, morphine concentrations ranged from <300 to 7,522μg/L with a median peak concentration of 5,239μg/L. The median first morphine-positive urine sample at 2,000μg/L cutoff concentration occurred at 6.6h (1.2-12.1), with the last positive from 2.6 to 18h after the second dose. No specimens were positive for codeine at a cutoff concentration of 2,000μg/L, but 20.2% exceeded 300μg/L, with peak concentrations of 658 μg/L (284-1540). The Roche Opiates II immunoassay had efficiencies greater than 96% for the 2000 and 300μg/L cutoffs. The CEDIA 6AM immunoassay had a specificity of 91%, while the Lin-Zhi assay had no false positive results. These data provide valuable information for interpreting urine opiate results. PMID:24887324

  7. Opiate users' knowledge about overdose prevention and naloxone in New York City: a focus group study

    Directory of Open Access Journals (Sweden)

    Galea Sandro

    2006-07-01

    Full Text Available Abstract Background Drug-induced and drug-related deaths have been increasing for the past decade throughout the US. In NYC, drug overdose accounts for nearly 900 deaths per year, a figure that exceeds the number of deaths each year from homicide. Naloxone, a highly effective opiate antagonist, has for decades been used by doctors and paramedics during emergency resuscitation after an opiate overdose. Following the lead of programs in Europe and the US who have successfully distributed take-home naloxone, the Overdose Prevention and Reversal Program at the Lower East Side Harm Reduction Center (LESHRC has started providing a similar resource for opiate users in NYC. Participants in the program receive a prescription for two doses of naloxone, with refills as needed, and comprehensive training to reduce overdose risk, administer naloxone, perform rescue breathing, and call 911. As of September 2005, 204 participants have received naloxone and been trained, and 40 have revived an overdosing friend or family member. While naloxone accessibility stands as a proven life-saving measure, some opiates users at LESHRC have expressed only minimal interest in naloxone use, due to past experiences and common misconceptions. Methods In order to improve the naloxone distribution program two focus groups were conducted in December 2004 with 13 opiate users at LESHRC to examine knowledge about overdose and overdose prevention. The focus groups assessed participants' (i experiences with overdose response, specifically naloxone (ii understanding and perceptions of naloxone, (iii comfort level with naloxone administration and (iv feedback about increasing the visibility and desirability of the naloxone distribution program. Results Analyses suggest that there is both support for and resistance to take-home naloxone, marked by enthusiasm for its potential role in reviving an overdosing individual, numerous misconceptions and negative views of its impact and use

  8. Prospective, randomized, controlled trial of thoracic epidural or patient-controlled opiate analgesia on perioperative quality of life.

    LENUS (Irish Health Repository)

    Ali, M

    2010-03-01

    Perioperative epidural analgesia provides continuous pain control and may have advantages over parenteral opiate administration. This study assessed the impact of epidural analgesia on quality of life (QOL) of patients undergoing major surgery.

  9. Opioid receptor trafficking and interaction in nociceptors

    Science.gov (United States)

    Zhang, X; Bao, L; Li, S

    2015-01-01

    Opiate analgesics such as morphine are often used for pain therapy. However, antinociceptive tolerance and dependence may develop with long-term use of these drugs. It was found that μ-opioid receptors can interact with δ-opioid receptors, and morphine antinociceptive tolerance can be reduced by blocking δ-opioid receptors. Recent studies have shown that μ- and δ-opioid receptors are co-expressed in a considerable number of small neurons in the dorsal root ganglion. The interaction of μ-opioid receptors with δ-opioid receptors in the nociceptive afferents is facilitated by the stimulus-induced cell-surface expression of δ-opioid receptors, and contributes to morphine tolerance. Further analysis of the molecular, cellular and neural circuit mechanisms that regulate the trafficking and interaction of opioid receptors and related signalling molecules in the pain pathway would help to elucidate the mechanism of opiate analgesia and improve pain therapy. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2 PMID:24611685

  10. Lifetime opiate exposure as an independent and interactive cardiovascular risk factor in males: a cross-sectional clinical study

    Directory of Open Access Journals (Sweden)

    Reece AS

    2013-10-01

    Full Text Available Albert S Reece, Gary K HulseSchool of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, WA, AustraliaIntroduction: While several studies have identified an increased incidence of cardiovascular disorders in opiate dependence, neither opiates as a cardiovascular risk factor nor their effect on central arterial function has been considered.Methods: Pulse wave analysis (SphygmoCor, AtCorMedical Pty Limited, Sydney, NSW, Australia was undertaken on a cohort of controls and opiate dependent patients and the results compared to their lifetime opiate exposure.Results: Controls (N = 401 were compared with 465 opiate dependent men. The mean (log ages were different and were found to be 28.80 ± 0.49 years versus 35.02 ± 0.39 years (P < 0.0001, respectively. Of the opiate dependent group, 87.7% were treated with buprenorphine, 8.8% with methadone, and 3.4% with naltrexone. Multiple regression analysis was used to adjust for chronologic age (CA. At CA of 60 years, the modeled age in the controls was 66.40 years, and that in the addicted group was 73.11 years, an advancement of 6.71 years, or 10.10%. Exacerbations of age dependent changes in central arterial stiffness, central pressures, pulse rate, ejection duration, diastolic duration, and subendocardial perfusion ratio by opiate dependence were all noted (P < 0.05. Current heroin dose, heroin duration, and the dose duration interaction were all significantly related to the vascular (or “reference” age (RA/CA ratio (all P < 0.006. After multivariate adjustment, the opiate dose duration was independently predictive of RA (P < 0.02. Opiate dose and/or duration were included in a further 25 terms.Conclusion: These data show that opiate use is not benign for the male cardiovascular system, but has a dose response relationship to central arterial stiffness and thus cardiovascular aging, acting independently and interactively with established cardiovascular risk factors

  11. Analysis of pharmacoepidemiologal indicators of consumption of opiates and opioids in St. Petersburg: trends in the early XXI century

    OpenAIRE

    M. V. Pchelintsev

    2015-01-01

    The article presents the author's self-retrieved data on study of pharmacoepidemiological indicators of consumption of opiates and opioids in St. Petersburg from 2001 to 2013. Pharmaco-epidemiological indicators of consumption of opioids in St. Petersburg and a number of countries are compared. Based on these estimates, the author suggests the ways to optimize provision of patients suffering intense acute and chronic pain with opiates and opioids.

  12. Analysis of pharmacoepidemiologal indicators of consumption of opiates and opioids in St. Petersburg: trends in the early XXI century

    Directory of Open Access Journals (Sweden)

    M. V. Pchelintsev

    2015-01-01

    Full Text Available The article presents the author's self-retrieved data on study of pharmacoepidemiological indicators of consumption of opiates and opioids in St. Petersburg from 2001 to 2013. Pharmaco-epidemiological indicators of consumption of opioids in St. Petersburg and a number of countries are compared. Based on these estimates, the author suggests the ways to optimize provision of patients suffering intense acute and chronic pain with opiates and opioids.

  13. Individual differences in initial morphine sensitivity as a predictor for the development of opiate addiction in rats.

    Science.gov (United States)

    Nishida, Kevin S; Park, Thomas Y; Lee, Bong Hyo; Ursano, Robert J; Choi, Kwang H

    2016-10-15

    Individuals report a wide range of analgesia to similar doses of opiates, and not all opiate users become addicted. This suggests that there may be certain predispositions that influence one to develop opiate addiction. We investigated the relationship between the individual differences in initial morphine sensitivity and the subsequent development of opiate addiction-like behavior using a hot plate test and an intravenous morphine self-administration (MSA) paradigm in rats. Using a median split of initial morphine antinociception, animals were defined as low antinociception (LA) and high antinociception (HA) groups. Thus, the LA group represents the animals that were less sensitive to initial morphine antinociception as compared to those of the HA group. The animals were allowed to self-administer either saline or morphine (0.5mg/kg/infusion, 4hr/day) 5days per week for 3 weeks. Spontaneous locomotor activity was measured on self-administration days 10 and 15. Individual differences in initial morphine sensitivity were not correlated with the amount of morphine self-administered by the animals on day 1. In the second-week of MSA, the LA group exhibited increased morphine intake and locomotor hyperactivity as compared to those of the HA group. Therefore, certain animals that are less sensitive to initial morphine antinociception may be susceptible to developing opiate addiction. The current findings may have clinical implications for future research on the biological mechanisms of opiate addiction and preclinical medication development.

  14. Molecular pharmacology of cell receptors for cardiac glycosides, opiates, ACTH and ion channel modulators

    Energy Technology Data Exchange (ETDEWEB)

    Hnatowich, M.R.

    1986-01-01

    The influence of light and oxygen on molecular interactions between the artificial food dye, erythrosine (ERY), and (/sup 3/H)ouabain ((/sup 3/H)OUA) binding sites on (Na/sup +/ + K/sup +/)-ATPase in rat brain and guinea pig heart was investigated. Putative endogenous digitalis-like factors (DLF's) were studied in four in vitro assays for cardiac glycosides. (/sup 3/H)Etorphine binding was characterized in rat brain homogenates, depleted of opioids, from animals acutely and chronically treated with morphine and naloxone, and either unstressed or cold-restraint-stressed. Binding sites for the ion channel modulators (/sup 3/H)verapamil ((/sup 3/H)VER) and (/sup 3/H) phencyclidine ((/sup 3/H)PCP) were characterized in rat brain.

  15. Desensitization of brain opiate receptor mechanisms by gonadal steroid treatments that stimulate luteinizing hormone secretion.

    Science.gov (United States)

    Berglund, L A; Derendorf, H; Simpkins, J W

    1988-06-01

    We studied the effects of two ovarian steroid treatments that induce proestrous-like surges in LH secretion on responsiveness to morphine sulfate (MS), as measured by induced hypothermic, antinociceptive, behavioral, and LH secretory changes. Ovariectomized rats received no steroids (OVX), 7.5 micrograms estradiol benzoate 2 days before the experiment (EB), or EB and then 5 mg progesterone 48 h later (EBP). MS administration coincided with the steroid-induced LH hypersecretion that occurs in the EB and EBP rats at 1530-1630 h. Serum LH concentrations were determined 30 min after administration of MS. In OVX and EB rats, MS caused a dose-dependent decrease in serum LH, but even 20 mg/kg MS did not alter serum LH during the EBP-induced LH surge. Brain-mediated morphine-induced analgesia was evaluated in the three steroid treatment groups from measurement of latency to pawlick on a hot plate. EB and EBP rats were less responsive than OVX rats to MS-induced antinociception. EB and EBP rats were also less responsive than OVX animals to the spinal cord-mediated analgesia due to MS, as calculated by tail-flick latency. MS-induced hypothermia revealed a responsiveness order of OVX greater than EB greater than EBP. Whereas MS caused a dose-dependent reduction in locomotor activity in OVX and EB rats, EBP rats showed marked hyperactivity at low MS doses and were less responsive to the suppression of locomotor activity at higher doses. These marked steroid-induced changes in MS responsiveness could not be explained by altered pharmacokinetic disposition of morphine. These data indicate that treatment with EBP, which stimulates a preovulatory-like LH surge, decreases the ability of MS to induce hypothermic, antinociceptive, and behavioral responses and abolishes its capacity to suppress LH release. These effects of gonadal steroids were not observed before the LH surge, which suggests that this surge is linked to the decline in MS sensitivity. Further, the diminished response to MS appears to be a function of the magnitude of the LH surge.

  16. ACTIVATION AND INTERNALIZATION OF THE μ-OPIOID RECEPTOR BY THE NEWLY DISCOVERED ENDOGENOUS AGONISTS, ENDOMORPHIN-1 AND ENDOMORPHIN-2

    OpenAIRE

    McConalogue, K; Grady, E. F.; MINNIS, J.; Balestra, B; Tonini, M; Brecha, N C; Bunnett, N. W.; Sternini, C.

    1999-01-01

    The multiple effects of opiate alkaloids, important therapeutic drugs used for pain control, are mediated by the neuronal μ-opioid receptor. Among the side effects of these drugs is a profound impairment of gastrointestinal transit. Endomorphins are opioid peptides recently isolated from the nervous system, which have high affinity and selectivity for μ-opioid receptors. Since the μ-opioid receptor undergoes ligand-induced receptor endocytosis in an agonist-dependent manner, we compared the a...

  17. Impact of substance abuse treatment on arrests among opiate users in Washington State.

    Science.gov (United States)

    Campbell, Kevin M; Deck, Dennis; Krupski, Antoinette

    2007-01-01

    Administrative data from Washington State's Division of Alcohol and Substance Abuse drive this three-year prospective study of the impact of substance abuse treatment on arrests among 12,962 opiate users receiving publicly funded substance abuse services. Using survival analysis, the risk of arrest among opiate users who receive substance abuse treatment is compared to those who do not receive treatment. Propensity scores control for client characteristics associated with admission to substance abuse treatment. Overall, a reduction in the risk of arrest was found among subjects in treatment (Hazard Ratio = 0.59-0.78, p < .05) and subjects successfully completing treatment (Hazard Ratio = 0.75, p < .05). Risk of arrest was elevated among those with a negative outcome to treatment (Hazard Ratio = 1.23, p < .05).

  18. Parenting beliefs and practices of opiate-addicted parents: concealment and taboo.

    Science.gov (United States)

    Hogan, Diane M

    2003-07-01

    The lifestyle associated with opiate dependence, including drug taking, the buying and selling of drugs, and contact with other drug users, carries potential risks for the safety and well-being of children of drug-using parents. Based on a qualitative interview study conducted with 50 opiate-dependent parents in Dublin, Ireland, the parenting beliefs and practices in relation to children's exposure to drugs and the associated lifestyle are described. Parents saw their lifestyle as potentially risky for their children and their families. The most common strategy adopted by parents was to conceal their drug-related activities and maintain a strict family taboo about these activities. Intervention programmes should be offered to support effective family communication about parental drug dependence.

  19. LC-MS-MS Method for Analysis of Opiates in Wastewater During Football Games II.

    Science.gov (United States)

    Gul, Waseem; Stamper, Brandon; Godfrey, Murrell; Gul, Shahbaz W; ElSohly, Mahmoud A

    2016-06-01

    Continuing our previous studies analyzing drugs of abuse in municipal wastewater, a method was developed for the analysis of opiates in wastewater samples using liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). Eight opiate drugs and metabolites were analyzed including codeine, hydrocodone, hydromorphone, 6-monoacetylmorphine (6-MAM, the primary urinary metabolite of heroin), morphine, norhydrocodone (the primary urinary metabolite of hydrocodone), oxycodone and oxymorphone. These drugs were chosen because of their widespread abuse. Wastewater samples were collected at both the Oxford Waste Water Treatment Plant in Oxford, Mississippi (MS) and the University Wastewater Treatment Plant in University, MS. These wastewater samples were collected on weekends in which the Ole Miss Rebel football team held home games (Vaught-Hemingway Stadium, University, MS 38677). The collected samples were analyzed using a validated method and found to contain codeine, hydrocodone, hydromorphone, morphine, norhydrocodone, oxycodone and oxymorphone. None of the samples contained 6-MAM.

  20. Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Adams Clive E

    2007-01-01

    Full Text Available Abstract Background Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with dihydrocodeine for detoxification from illicit opiates in primary care. Methods Open label randomised controlled trial in NHS Primary Care (General Practices, Leeds, UK. Sixty consenting adults using illicit opiates received either daily sublingual buprenorphine or daily oral dihydrocodeine. Reducing regimens for both interventions were at the discretion of prescribing doctor within a standard regimen of not more than 15 days. Primary outcome was abstinence from illicit opiates at final prescription as indicated by a urine sample. Secondary outcomes during detoxification period and at three and six months post detoxification were recorded. Results Only 23% completed the prescribed course of detoxification medication and gave a urine sample on collection of their final prescription. Risk of non-completion of detoxification was reduced if allocated buprenorphine (68% vs 88%, RR 0.58 CI 0.35–0.96, p = 0.065. A higher proportion of people allocated to buprenorphine provided a clean urine sample compared with those who received dihydrocodeine (21% vs 3%, RR 2.06 CI 1.33–3.21, p = 0.028. People allocated to buprenorphine had fewer visits to professional carers during detoxification and more were abstinent at three months (10 vs 4, RR 1.55 CI 0.96–2.52 and six months post detoxification (7 vs 3, RR 1.45 CI 0.84–2.49. Conclusion Informative randomised trials evaluating routine care within the primary care setting are possible amongst drug using populations. This small study generates unique data on commonly used treatment regimens.

  1. Neurofeedback training for opiate addiction: improvement of mental health and craving.

    Science.gov (United States)

    Dehghani-Arani, Fateme; Rostami, Reza; Nadali, Hosein

    2013-06-01

    Psychological improvements in patients with substance use disorders have been reported after neurofeedback treatment. However, neurofeedback has not been commonly accepted as a treatment for substance dependence. This study was carried out to examine the effectiveness of this therapeutic method for opiate dependence disorder. The specific aim was to investigate whether treatment leads to any changes in mental health and substance craving. In this experimental study with a pre-post test design, 20 opiate dependent patients undergoing Methadone or Buprenorphine maintenance treatment were examined and matched and randomized into two groups. While both experimental and control groups received their usual maintenance treatment, the experimental group received 30 sessions of neurofeedback treatment in addition. The neurofeedback treatment consisted of sensory motor rhythm training on Cz, followed by an alpha-theta protocol on Pz. Data from the general health questionnaire and a heroin craving questionnaire were collected before and after treatment. Multivariate analysis of covariance showed that the experimental group achieved improvement in somatic symptoms, depression, and total score in general mental health; and in anticipation of positive outcome, desire to use opioid, and relief from withdrawal of craving in comparison with the control group. The study supports the effectiveness of neurofeedback training as a therapeutic method in opiate dependence disorder, in supplement to pharmacotherapy.

  2. Performance of immunoassays in screening for opiates, cannabinoids and amphetamines in post-mortem blood.

    Science.gov (United States)

    Hino, Yukiko; Ojanperä, Ilkka; Rasanen, Ilpo; Vuori, Erkki

    2003-01-28

    Several immunoassay methods for screening of abused drugs in whole blood were evaluated in post-mortem forensic toxicology. Blood samples known to be positive or negative for opiates, cannabinoids or amphetamines by gas chromatography-mass spectrometry (GC-MS) were analysed by EMIT II Plus and EMIT d.a.u., Syva RapidTest and Triage 8 after acetone precipitation. In these experiments, the EMIT immunoassay method was modified by using the Dade Behring VIVA analyser to detect substances more sensitively. Low concentrations of abused drugs were detected in blood samples. The sensitivities of the modified EMIT method for opiates, cannabinoids and amphetamines were 100, 86 and 98%, respectively, whereas the values were below 86% with the other methods. The specificities of all immunoassay methods for opiates and cannabinoids were 83% or above but 51-85% for amphetamines. Sample rejection occurred in a few cases with the EMIT amphetamine assays. The modified EMIT immunoassay system presented here seems to be useful for screening of drugs of abuse in post-mortem blood samples, especially when urine is not available.

  3. ACTH-like peptides increase pain sensitivity and antagonize opiate analgesia

    Science.gov (United States)

    Heybach, J. P.; Vernikos, J.

    1981-01-01

    The role of the pituitary and of ACTH in pain sensitivity was investigated in the rat. Pain sensitivity was assessed by measuring paw-lick and jump latencies in response to being placed on a grid at 55 C. Hypophysectomy reduced pain sensitivity, and this effect was reversed by the intracerebroventricular (ICV) injection of the opiate antagonist naloxone. Similarly, the analgesia produced by a dose of morphine was antagonized by the administration of ACTH or alpha-MSH. The peripheral injection of ACTH or alpha-MSH in normal rats did not increase pain sensitivity. However, ACTH administered ICV increased pain sensivity within 10 min. The results indicate that the pituitary is the source of an endogenous opiate antagonist and hyperalgesic factor and that this factor is ACTH or an ACTH-like peptide. This activity resides in the N-terminal portion of the ACTH molecule since ACTH sub 4-10 is not active in this respect, nor does this activity require a free N-terminal serine since alpha-MSH appears to be almost as potent as the ACTH sub 1-24 peptide. It is concluded that ACTH-like peptides of pituitary origin act as endogenous hyperalgesic and opiate antagonistic factors.

  4. NCK2 is significantly associated with opiates addiction in African-origin men.

    Science.gov (United States)

    Liu, Zhifa; Guo, Xiaobo; Jiang, Yuan; Zhang, Heping

    2013-01-01

    Substance dependence is a complex environmental and genetic disorder with significant social and medical concerns. Understanding the etiology of substance dependence is imperative to the development of effective treatment and prevention strategies. To this end, substantial effort has been made to identify genes underlying substance dependence, and in recent years, genome-wide association studies (GWASs) have led to discoveries of numerous genetic variants for complex diseases including substance dependence. Most of the GWAS discoveries were only based on single nucleotide polymorphisms (SNPs) and a single dichotomized outcome. By employing both SNP- and gene-based methods of analysis, we identified a strong (odds ratio = 13.87) and significant (P value = 1.33E - 11) association of an SNP in the NCK2 gene on chromosome 2 with opiates addiction in African-origin men. Codependence analysis also identified a genome-wide significant association between NCK2 and comorbidity of substance dependence (P value = 3.65E - 08) in African-origin men. Furthermore, we observed that the association between the NCK2 gene (P value = 3.12E - 10) and opiates addiction reached the gene-based genome-wide significant level. In summary, our findings provided the first evidence for the involvement of NCK2 in the susceptibility to opiates addiction and further revealed the racial and gender specificities of its impact.

  5. The Effectiveness of Psychodrama in Relapse Prevention and Reducing Depression among Opiate-Dependent Men

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    s dehnavi

    2015-09-01

    Full Text Available Objective: The current study aimed to investigate the effectiveness of psychodrama therapy in relapse prevention (RP and the reduction of depression among opiate-dependent male patients. Method: A quasi-experimental research design along with pre-post tests and follow-up and control group was employed for this study. Using convenience sampling method, the number of 20 opiate-dependent men who had referred to addiction treatment clinics in Kermanshah (Iran and successfully passed detoxification program was randomly selected as the participants of the study. The experimental group participated in a twelve-session therapy plan during six weeks. Beck Depression Inventory (BDI was used for data collection purposes. Results: The results of ANCOVA revealed the existence of a significant difference between the two groups in the post-test and follow-up scores. Conclusion: According to the findings, it can be argued that psychodrama intervention can be used as an effective program in the reduction of depression and relapse prevention among opiate-dependent men.

  6. Initiation of opiate addiction in a Canadian prison: a case report

    Directory of Open Access Journals (Sweden)

    Lim Ronald

    2006-03-01

    Full Text Available Abstract Background In North America, the harms of illicit drug use have been responded to primarily through law enforcement interventions. This strategy has resulted in record populations of addicted individuals being incarcerated in both Canada and the United States. The incarceration of non-violent drug offenders has become increasingly controversial as studies demonstrate the harms, including elevated HIV risk behavior, of incarcerating injection drug users. Other harms, such as the initiation of illicit drug use by prison inmates who previously did not use drugs, have been less commonly described. Case Presentation We report on the case of an individual who initiated non-injection opiate use in a Canadian prison and developed an addiction to the drug. Upon release into the community, the individual continued using opiates and sought treatment at a clinic. The patient feared that he might initiate injection use of opiates if his cravings could not be controlled. The patient was placed on methadone maintenance therapy. Conclusion While anecdotal reports indicate that initiation in prison of the use of addictive illicit substances is frequent, documentation through clinical experience is rare, and the public health implications of this behavior have not been given sufficient attention in the literature. Strategies of incarcerating non-violent drug offenders and attempting to keep illicit drugs out of prisons have not reduced the harms and costs of illicit drug use. Effective, practical alternatives are urgently needed; expanded community diversion programs for non-violent drug offenders deserve particular attention.

  7. Efficacy of Cognitive Behavioral Therapy on Opiate Use and Retention in Methadone Maintenance Treatment in China: A Randomised Trial.

    Directory of Open Access Journals (Sweden)

    Shujun Pan

    Full Text Available Methadone maintenance treatment (MMT is widely available in China; but, high rates of illicit opiate use and dropout are problematic. The aim of this study was to test whether cognitive behavioral therapy (CBT in conjunction with MMT can improve treatment retention and reduce opiate use.A total of 240 opiate-dependent patients in community-based MMT clinics were randomly assigned to either weekly CBT plus standard MMT (CBT group, n=120 or standard MMT (control group, n=120 for 26 weeks. The primary outcomes were treatment retention and opiate-negative urine test results at 12 weeks and 26 weeks. The secondary outcomes were composite scores on the Addiction Severity Index (ASI and total scores on the Perceived Stress Scale (PSS at 12 weeks and 26 weeks.Compared to the control group in standard MMT, the CBT group had higher proportion of opiate-negative urine tests at both 12 weeks (59% vs. 69%, p<0.05 and 26 weeks (63% vs. 73%, p<0.05; however, the retention rates at 12 weeks (73.3% vs. 74.2%, p=0.88 and 26 weeks were not different (55.8% vs. 64.2%, p=0.19 between the two groups. At both 12 and 26 weeks, all of the ASI component scores and PSS total scores in the CBT group and control group decreased from baseline; but the CBT group exhibited more decreases in ASI employment scores at week 26 and more decrease in the PSS total score at week 12 and week 26.CBT counselling is effective in reducing opiate use and improving employment function and in decreasing stress level for opiate-dependent patients in MMT in China.ClinicalTrials.gov NCT01144390.

  8. Employment-based abstinence reinforcement promotes opiate and cocaine abstinence in out-of-treatment injection drug users.

    Science.gov (United States)

    Holtyn, August F; Koffarnus, Mikhail N; DeFulio, Anthony; Sigurdsson, Sigurdur O; Strain, Eric C; Schwartz, Robert P; Silverman, Kenneth

    2014-01-01

    We examined the use of employment-based abstinence reinforcement in out-of-treatment injection drug users, in this secondary analysis of a previously reported trial. Participants (N = 33) could work in the therapeutic workplace, a model employment-based program for drug addiction, for 30 weeks and could earn approximately $10 per hr. During a 4-week induction, participants only had to work to earn pay. After induction, access to the workplace was contingent on enrollment in methadone treatment. After participants met the methadone contingency for 3 weeks, they had to provide opiate-negative urine samples to maintain maximum pay. After participants met those contingencies for 3 weeks, they had to provide opiate- and cocaine-negative urine samples to maintain maximum pay. The percentage of drug-negative urine samples remained stable until the abstinence reinforcement contingency for each drug was applied. The percentage of opiate- and cocaine-negative urine samples increased abruptly and significantly after the opiate- and cocaine-abstinence contingencies, respectively, were applied. These results demonstrate that the sequential administration of employment-based abstinence reinforcement can increase opiate and cocaine abstinence among out-of-treatment injection drug users.

  9. Auditory sensitivity in opiate addicts with and without a history of noise exposure

    Directory of Open Access Journals (Sweden)

    Vishakha Rawool

    2011-01-01

    Full Text Available Several case reports suggest that some individuals are susceptible to hearing loss from opioids. A combination of noise and opium exposure is possible in either occupational setting such as military service or recreational settings. According to the Drug Enforcement Agency of the U.S. Department of Justice, prescriptions for opiate-based drugs have skyrocketed in the past decade. Since both opium and noise independently can cause hearing loss, it is important to know the prevalence of hearing loss among individuals who are exposed to opium or both opium and noise. The purpose of this research was to evaluate auditory sensitivity in individuals with a history of opium abuse and/or occupational or nonoccupational noise exposure. Twenty-three men who reported opiate abuse served as participants in the study. Four of the individuals reported no history of noise exposure, 12 reported hobby-related noise exposure, 7 reported occupational noise exposure including 2 who also reported hobby-related noise exposure. Fifty percent (2/4 of the individuals without any noise exposure had a hearing loss confirming previous reports that some of the population is vulnerable to the ototoxic effects of opioids. The percentage of population with hearing loss increased with hobby-related (58% and occupational noise exposure (100%. Mixed MANOVA revealed a significant ear, frequency, and noise exposure interaction. Health professionals need to be aware of the possible ototoxic effects of opioids, since early detection of hearing loss from opium abuse may lead to cessation of abuse and further progression of hearing loss. The possibility that opium abuse may interact with noise exposure in determining auditory thresholds needs to be considered in noise exposed individuals who are addicted to opiates. Possible mechanisms of cochlear damage from opium abuse, possible reasons for individual susceptibility, and recommendations for future studies are presented in the article.

  10. Frontal Metabolite Concentration Deficits in Opiate Dependence Relate to Substance Use, Cognition, and Self-Regulation

    Science.gov (United States)

    Murray, Donna E; Durazzo, Timothy C; Schmidt, Thomas P; Abé, Christoph; Guydish, Joseph; Meyerhoff, Dieter J

    2016-01-01

    Objective Proton magnetic resonance spectroscopy (1H MRS) in opiate dependence showed abnormalities in neuronal viability and glutamate concentration in the anterior cingulate cortex (ACC). Metabolite levels in dorsolateral prefrontal cortex (DLPFC) or orbitofrontal cortex (OFC) and their neuropsychological correlates have not been investigated in opiate dependence. Methods Single-volume proton MRS at 4 Tesla and neuropsychological testing were conducted in 21 opiate-dependent individuals (OD) on buprenorphine maintenance therapy. Results were compared to 28 controls (CON) and 35 alcohol-dependent individuals (ALC), commonly investigated treatment-seekers providing context for OD evaluation. Metabolite concentrations were measured from ACC, DLPFC, OFC and parieto-occipital cortical (POC) regions. Results Compared to CON, OD had lower concentrations of N-acetylaspartate (NAA), glutamate (Glu), creatine +phosphocreatine (Cr) and myo-Inositol (mI) in the DLPFC and lower NAA, Cr, and mI in the ACC. OD, ALC, and CON were equivalent on metabolite levels in the POC and γ-aminobutyric acid (GABA) concentration did not differ between groups in any region. In OD, prefrontal metabolite deficits in ACC Glu as well as DLPFC NAA and choline containing metabolites (Cho) correlated with poorer working memory, executive and visuospatial functioning; metabolite deficits in DLPFC Glu and ACC GABA and Cr correlated with substance use measures. In the OFC of OD, Glu and choline-containing metabolites were elevated and lower Cr concentration related to higher nonplanning impulsivity. Compared to 3 week abstinent ALC, OD had significant DLPFC metabolite deficits. Conclusion The anterior frontal metabolite profile of OD differed significantly from that of CON and ALC. The frontal lobe metabolite abnormalities in OD and their neuropsychological correlates may play a role in treatment outcome and could be explored as specific targets for improved OD treatment. PMID:27695638

  11. Lifetime ATS use and increased HIV risk among not-in-treatment opiate injectors in Malaysia

    Science.gov (United States)

    Chawarski, Marek C.; Vicknasingam, Balasingam; Mazlan, Mahmud; Schottenfeld, Richard S.

    2015-01-01

    Background Malaysia has been experiencing significant drug abuse problems since the 1970s, and drug abuse is the major driver of HIV transmission in Malaysia. We investigated risk factors for HIV associated with use of amphetamine type stimulants (ATS) among not-in-treatment opiate injectors in Malaysia. Methods Between October of 2006 and May of 2008, we conducted a series of surveys in three major urban areas of Malaysia. A total of 732 opiate IDUs (679 males and 53 females) were enrolled in the three surveys. The survey instruments consisted of a structured interview on demographic characteristics, drug use history (including year of first use, and past month history of use of illicit drugs; lifetime and past month history of IDU or needle or equipment sharing), and HIV status. Results There were 194/704 (27.6%) HIV positive participants in the sample. Two factors were significantly associated with HIV infection in this sample: lifetime history of ATS use (OR [95%CI]: 2.3 [1.5–3.6]) and lifetime history of sharing of injection equipment (OR [95% CI]: 4.2 [1.8–9.8]). Both HIV-positive and HIV-negative participants reported high levels of current needle/equipment sharing practices: 82% vs. 75%, respectively. Conclusions ATS use spread rapidly in the study sample after 1997 and is associated with an increased risk of HIV infection in this population already at high risk because of opiate IDU. Out-of-treatment IDUs in Malaysia engage in high risk behaviors regardless of their HIV status. Increased education and public health prevention measures are needed to reduce HIV transmission risks in this population. PMID:22266088

  12. Opiate System Mediate the Antinociceptive Effects of Coriandrum sativum in Mice.

    Science.gov (United States)

    Taherian, Abbas Ali; Vafaei, Abbas Ali; Ameri, Javad

    2012-01-01

    Our previous study showed that Coriandrum sativum (CS) has antinociceptive effects, but the mechanisms that mediate this effect are not clear. The present study was designed to test the role of opiate system in the antinociceptive effects of CS on acute and chronic pain in mice using Hot Plate (HP), Tail Flick (TF) and Formalin (FT) tests and also to compare its effect with dexamethasone (DEX) and stress (ST). Young adult male albino mice (25-30 g) in 33 groups (n = 8 in each group) were used in this study. CS (125 250, 500 and 1000 mg/Kg IP), DEX (0.5, 1 and 2 mg/Kg IP), vehicle (VEH) or swim stress were used 30 min before the pain evaluation tests. Acute and chronic pain was assessed by HP, TF and FT models. In addition, Naloxone (NAL, 2 mg/Kg, IP) was injected 15 min before the CS extract administration in order to assess the role of opiate system in the antinociception of CS. Results indicated that CS, DEX and ST have analgesic effects (p < 0.01) in comparison with the control group and higher dose of CS was more effective (p < 0.001). Besides, pretreatment of NAL modulates the antinociceptive effects of CS in all models (p < 0.001). The above findings showed that CS, DEX and ST have modulator effects on pain. These findings further indicate that the CS extract has more analgesic effects than DEX and ST and also provides the evidence for the existence of an interaction between antinociceptive effects of CS and opiate system.

  13. Women and addiction (alcohol and opiates: Comparative analysis of psychosocial aspects

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    Raketić Diana

    2013-01-01

    Full Text Available Introduction. Nowadays women constitute one third of all addicts. In the last decade, there has been a remarkable growth in scientific interest in biochemical and psychosocial aspects of women’s addiction. Many researches point out the specific character of women’s addiction. Objective. The aim of the study was to assess and compare psychosocial aspects, including the socio-demographic characteristics as well as the specific aspects of functioning of family and interpersonal relationships of the subjects addicted to opiates and alcohol. Methods. There were two substance addict groups (32 and 30 subjects addicted to drugs and alcohol, respectively and the control group, consisting of 30 subjects (no substance addiction. A socio-demo- graphic data questionnaire and semi-structured Addiction Severity Index (ASI interview were used. Results. The results of the research indicated that there were statistically significant differences between the compared groups in respect to the age of the subjects, family history of addiction disorders, education, parenthood, employment work status, and marital status. The subjects addicted to opiates differed significantly in respect to manifestation of aggressive, delinquent behaviour, infectious diseases, presence of addicts-partnerships, but there were no significant differences in relation to physical abuse, sexual abuse and self-assessment of depression. Conclusion. The results of this research suggest that subjects addicted to opiates differed largely from the subjects addicted to alcohol in terms of the age of the subjects, education level, family relationships, partnerships and social relationships, which all have to be taken into consideration when designing a therapy protocol and planning activities for prevention.

  14. [Analytical validation of a chromatographic method dedicated to search and identify natural and semi-synthetic opiates].

    Science.gov (United States)

    Dubois, Nathalie; Counerotte, Stéphane; Goffin, Eric; Pirotte, Bernard; Charlier, Corinne

    2014-01-01

    The identification of a product absorbed by an opiate consumer is sometimes problematic since there is no specific biomarker for all molecules. We developed an ultra-high pressure liquid chromatography coupled to tandem mass spectrometry technique which allows the identification and the quantification of 25 opiates in plasma. The sample preparation consists in a solid-phase extraction on Oasis MCX cartridges (Waters). The method has been validated according to FDA criteria completely for 21 substances and with some reservations for the remaining 4 analytes. This method has been applied to 80 patients treated at the University Hospital of Liege for whom the screening of opiates was positive. The identification of the product consumed was effective in 86% of cases.

  15. Parallel increases in sister chromatid exchanges at base level and with UV treatment in human opiate users

    Energy Technology Data Exchange (ETDEWEB)

    Shafer, D.A.; Falek, A.; Madden, J.J.; Tadayon, F.; Pline, M. (Georgia Mental Health Inst., Atlanta (USA). Human Genetics Research Lab.; Emory Univ., Atlanta, GA (USA). Dept. of Psychiatry); Bokos, P.J. (Interventions, Chicago, IL (USA)); Kuehnle, J.C.; Mendelson, J. (McLean Hospital, Belmont, MA (USA). Alcohol and Drug Abuse Research Center)

    1983-04-01

    The SCE base level frequency and SCE levels induced by far-UV (254 nm) treatment of cells in early G/sub 1/ and early S phases of the cell cycle were significantly higher in leukocytes from heroin addicts as compared to controls. The increased SCE levels in addicts was greatest at base level and smallest after UV irradiation of cells in S phase. These results corrobate and extend our previous findings of increased chromosome damage and reduced DNA-repair synthesis in heroin users. Since opiates do not directly damage DNA, the elevated cytogenetic effects associated with opiate use probably arise from secondary promotional effects related to opiate-mediated alterations in leukocyte metabolism.

  16. Label-free porous silicon immunosensor for broad detection of opiates in a blind clinical study and results comparison to commercial analytical chemistry techniques.

    Science.gov (United States)

    Bonanno, Lisa M; Kwong, Tai C; DeLouise, Lisa A

    2010-12-01

    In this work, we evaluate for the first time the performance of a label-free porous silicon (PSi) immunosensor assay in a blind clinical study designed to screen authentic patient urine specimens for a broad range of opiates. The PSi opiate immunosensor achieved 96% concordance with liquid chromatography-mass spectrometry/tandem mass spectrometry (LC-MS/MS) results on samples that underwent standard opiate testing (n = 50). In addition, successful detection of a commonly abused opiate, oxycodone, resulted in 100% qualitative agreement between the PSi opiate sensor and LC-MS/MS. In contrast, a commercial broad opiate immunoassay technique (CEDIA) achieved 65% qualitative concordance with LC-MS/MS. Evaluation of important performance attributes including precision, accuracy, and recovery was completed on blank urine specimens spiked with test analytes. Variability of morphine detection as a model opiate target was <9% both within-run and between-day at and above the cutoff limit of 300 ng mL(-1). This study validates the analytical screening capability of label-free PSi opiate immunosensors in authentic patient samples and is the first semiquantitative demonstration of the technology's successful clinical use. These results motivate future development of label-free PSi technology to reduce complexity and cost of diagnostic testing particularly in a point-of-care setting.

  17. Deficit of circulating stem – progenitor cells in opiate addiction: a pilot study

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    Davidson Peter

    2007-07-01

    Full Text Available Abstract A substantial literature describes the capacity of all addictive drugs to slow cell growth and potentiate apoptosis. Flow cytometry was used as a means to compare two lineages of circulating progenitor cells in addicted patients. Buprenorphine treated opiate addicts were compared with medical patients. Peripheral venous blood CD34+ CD45+ double positive cells were counted as haemopoietic stem cells (HSC's, and CD34+ KDR+ (VEGFR2+ cells were taken as endothelial progenitor cells (EPC's. 10 opiate dependent patients with substance use disorder (SUD and 11 non-addicted (N-SUD were studied. The ages were (mean + S.D. 36.2 + 8.6 and 56.4 + 18.6 respectively (P 0.15, OR = 0.09, 95% C.I. 0.01–0.97, a finding of some interest given the substantially older age of the N-SUD group. These laboratory data are thus consistent with clinical data suggesting accelerated ageing in addicted humans and implicate the important stem cell pool in both addiction toxicology and ageing. They carry important policy implications for understanding the fundamental toxicology of addiction, and suggest that the toxicity both of addiction itself and of indefinite agonist maintenance therapies may have been seriously underestimated.

  18. For lack of wanting: Discourses of desire in Ukrainian opiate substitution therapy programs.

    Science.gov (United States)

    Carroll, Jennifer J

    2016-04-01

    Available treatments for addiction and substance abuse in Ukraine have been shaped by the economic, political, and social shifts that have followed the country's independence. The introduction of methadone-based opiate substitution therapy (OST) for opiate addicts is especially representative of this. Biomedical paradigms of addiction, its etiology, and its treatment, promoted and paid for by international donors and elite global health entities, are being met by Ukrainian notions of personhood and psychology in both public discourse and clinical settings. Ukrainian physicians who work in OST programs frequently reference desire (желание) as the most significant factor in determining the success or failure of treatment. They refer to a desire to be treated, desire to get better, desire to live. The moralized imperative to possess this desire to get better is, in many ways, a reflection of how addiction and the addicted psyche is constructed and understood in the Ukrainian context. By exploring discourses of desire in narratives of addiction and treatment, I examine how notions of psychology, will, and self-control intersect, shaping the subjectivity, agency, and daily experiences of this vulnerable population.

  19. Involvement of protein degradation by the ubiquitin proteasome system in opiate addictive behaviors.

    Science.gov (United States)

    Massaly, Nicolas; Dahan, Lionel; Baudonnat, Mathieu; Hovnanian, Caroline; Rekik, Khaoula; Solinas, Marcello; David, Vincent; Pech, Stéphane; Zajac, Jean-Marie; Roullet, Pascal; Mouledous, Lionel; Frances, Bernard

    2013-03-01

    Plastic changes in the nucleus accumbens (NAcc), a structure occupying a key position in the neural circuitry related to motivation, are among the critical cellular processes responsible for drug addiction. During the last decade, it has been shown that memory formation and related neuronal plasticity may rely not only on protein synthesis but also on protein degradation by the ubiquitin proteasome system (UPS). In this study, we assess the role of protein degradation in the NAcc in opiate-related behaviors. For this purpose, we coupled behavioral experiments to intra-accumbens injections of lactacystin, an inhibitor of the UPS. We show that protein degradation in the NAcc is mandatory for a full range of animal models of opiate addiction including morphine locomotor sensitization, morphine conditioned place preference, intra-ventral tegmental area morphine self-administration and intra-venous heroin self-administration but not for discrimination learning rewarded by highly palatable food. This study provides the first evidence of a specific role of protein degradation by the UPS in addiction.

  20. Effectiveness of Positive Psychotherapy in Improving Opiate Addicts’ Quality of Life

    Directory of Open Access Journals (Sweden)

    P Porzoor

    2016-02-01

    Full Text Available Objective: This study was aimed to assess the effectiveness of positive psychotherapy based on quality of life in improving opiate addicts’ quality of life. Method: A quasi experimental research design long with control group and pre-test, post-test and follow-up was employed for the conduct of this study. All the opiate addicts referring to treatment centers of Ardebil city in 2013 constituted the statistical population of the study and the number of 36 participants was selected as the sample via purposive sampling and randomly assigned into experimental and control groups. Quality-of-life-based psychotherapy was conducted on the experimental group in 8 sessions while the control group received no intervention. Quality of life questionnaire was used for data collection purposes. Results: The results suggested the effectiveness of the intervention in quality of life. Conclusion: This intervention, which is formed from the combination positive psychology and cognitive-behavioral approach, can be used as an effective treatment method.

  1. A national study of the retention of Irish opiate users in methadone substitution treatment

    LENUS (Irish Health Repository)

    Mullen, Louise

    2012-07-02

    Background: Retention in treatment is a key indicator of methadone treatment success. The study aims to identify factors that are associated with retention. Objectives: To determine retention in treatment at 12 months for Irish opiate users in methadone substitution treatment and to indicate factors that increase the likelihood of retention. Methods: National cohort study of randomly selected opiate users commencing methadone treatment in 1999, 2001, and 2003 (n = 1269). Results: Sixty-one percent of patients attending methadone treatment remained in continuous treatment for more than 1 year. Retention in treatment at 12 months was associated with age, gender, facility type, and methadone dose. Age and gender were no longer significant when adjusted for other variables in the model. Those who attended a specialist site were twice as likely to leave methadone treatment within 12 months compared with those who attended a primary care physician. The most important predictor of retention in treatment was methadone dose. Those who received <60 mg of methadone were three times more likely to leave treatment. Conclusion: Retention in methadone treatment is high in Ireland in a variety of settings. The main factors influencing retention in methadone treatment was an adequate methadone dose and access to a range of treatment settings including from primary care physicians. Scientific Significance: Providing an adequate dose of methadone during treatment will increase the likelihood of treatment retention. Methadone treatment by the primary care physician is a successful method of retaining opioid users in treatment.

  2. Roche DAT immunoassay: sensitivity and specificity testing for amphetamines, cocaine, and opiates in oral fluid.

    Science.gov (United States)

    Crooks, C Richard; Brown, Sue

    2010-03-01

    Laboratory testing of oral fluid for drugs of abuse continues to expand in the workplace, legal, treatment, and health settings. In this study, we assessed recently developed homogeneous Roche DAT screening assays for amphetamines, cocaine metabolite [benzoylecgonine (BZE)], methamphetamines, and opiates in oral fluid. Precision and accuracy were assessed using control samples at +/-25% of cutoff. Sensitivity, specificity, and agreement compared to liquid chromatography-tandem mass spectrometry (LC-MS-MS) was assessed by analysis of oral fluid specimens collected from 994 subjects enrolled in a drug treatment or probation and parole drug-testing program. An additional 180 research specimens from Kroll Laboratories were analyzed for amphetamine and methamphetamine. Screening cutoff concentrations (ng/mL) were as follows: amphetamines, 40; cocaine metabolite, 3; methamphetamines, 40; and opiates, 10. LC-MS-MS analyses were performed with the following cutoff concentrations (ng/mL): amphetamine, 40; BZE, 2.0; methamphetamine, 40; and codeine or morphine, 10. The percent coefficient of variation ranged from 3.4% to 7.3%. Sensitivity and specificity of the Roche DAT assays compared to LC-MS-MS were > 94%, and agreement was > 96% for the four assays. The performance of the Roche DAT assays suggests these new homogeneous screening assays will be an attractive alternative to existing more labor-intensive enzyme immunoassays.

  3. Involvement of endogenous opiates in regulation of gastric emptying of fat test meals in mice

    Energy Technology Data Exchange (ETDEWEB)

    Fioramonti, J.; Fargeas, M.J.; Bueno, L.

    1988-08-01

    The role of endogenous opioids and cholecystokinin (CCK) in gastric emptying was investigated in mice killed 30 min after gavage with /sup 51/Cr-radiolabeled liquid meals. The meals consisted of 0.5 ml of milk or one of five synthetic meals containing arabic gum, glucose and/or arachis oil and/or casein. Naloxone (0.1 mg/kg sc) significantly (P less than 0.01) accelerated gastric emptying of milk and meals containing fat but did not modify gastric emptying of nonfat meals. The CCK antagonist asperlicin (0.1 mg/kg ip) increased by 25% gastric emptying of milk. The gastric emptying of meals containing glucose and casein but not fat was reduced after administration of the COOH-terminal octapeptide of cholecystokinin (CCK-8, 4 micrograms/kg ip). This decrease was antagonized by both asperlicin (10 mg/kg ip) and naloxone (0.1 mg/kg sc). Intracerebroventricular (icv) administration of an opiate antagonist that poorly crosses the blood-brain barrier, methyl levallorphan (10 micrograms/kg), did not modify gastric emptying of milk but accelerated it when peripherally administered (0.1 mg/kg sc). Similarly, asperlicin (icv) administered at a dose of 1 mg/kg did not affect milk emptying. These results indicate that endogenous opiates are involved at peripheral levels in the regulation of gastric emptying of fat meals only and that such regulation involves release of CCK.

  4. Cloning of opioid receptors in common carp (Cyprinus carpio L.) and their involvement in regulation of stress and immune response

    NARCIS (Netherlands)

    Chadzinska, M.K.; Hermsen, G.J.; Savelkoul, H.F.J.; Verburg-van Kemenade, B.M.L.

    2009-01-01

    In mammals opiate alkaloids and endogenous opioid peptides exert their physiological and pharmacological actions through opioid receptors (MOR, DOR and KOR) expressed not only on neuroendocrine cells but also on leukocytes. Therefore, opioids can modulate the immune response. We cloned and sequenced

  5. The Metabotropic Glutamate 5 Receptor Modulates Extinction and Reinstatement of Methamphetamine-Seeking in Mice

    OpenAIRE

    Rose Chesworth; Brown, Robyn M.; Jee Hyun Kim; Lawrence, Andrew J.

    2013-01-01

    Methamphetamine (METH) is a highly addictive psychostimulant with no therapeutics registered to assist addicts in discontinuing use. Glutamatergic dysfunction has been implicated in the development and maintenance of addiction. We sought to assess the involvement of the metabotropic glutamate 5 receptor (mGlu5) in behaviours relevant to METH addiction because this receptor has been implicated in the actions of other drugs of abuse, including alcohol, cocaine and opiates. mGlu5 knockout (KO) m...

  6. Endogenous Opioid-Induced Neuroplasticity of Dopaminergic Neurons in the Ventral Tegmental Area Influences Natural and Opiate Reward

    NARCIS (Netherlands)

    Pitchers, Kyle K.; Coppens, Caroline M.; Beloate, Lauren N.; Fuller, Jonathan; Van, Sandy; Frohmader, Karla S.; Laviolette, Steven R.; Lehman, Michael N.; Coolen, Lique M.

    2014-01-01

    Natural reward and drugs of abuse converge on the mesolimbic pathway and activate common mechanism of neural plasticity in the nucleus accumbens. Chronic exposure to opiates induces plasticity in dopaminergic neurons of the ventral tegmental area (VTA), which regulates morphine reward tolerance. Her

  7. Investigating the Relationship between Sexual and Chemical Addictions by Comparing Executive Function in Pedophiles, Opiate Addicts and Healthy Controls

    Science.gov (United States)

    Cohen, Lisa J.; Nesci, Cristina; Steinfeld, Matthew; Haeri, Sophia; Galynker, Igor

    2011-01-01

    Disorders of driven sexual behavior have been conceptualized as sexual addictions. In the following study, we compared 51 subjects with pedophilia, 53 subjects with opiate addiction, and 84 healthy control subjects on neuropsychological tests that tap executive functions. The test battery included the Wisconsin Card Sorting Test (WCST), Stroop Color-Word Test, the Matching Familiar Figures Test (MFFT), Porteus Mazes, Controlled Word Association (COWA), and Trailmaking Test. The groups differed on tests of cognitive flexibility and set switching (WCST), sustained attention (Stroop), and impulsivity (MFFT and Porteus Mazes). There were no differences on verbal fluency (COWA). The subjects with pedophilia differed significantly from those with opiate addiction on several tests, with longer latency to response on MFFT and fewer completed mazes but also fewer errors on Porteus Mazes. Thus, while both subjects with pedophilia and those with opiate addiction show executive dysfunction, the nature of that dysfunction may differ between the two groups; specifically, opiate addicted subjects may be more prone to cognitive impulsivity. PMID:21107145

  8. Sensitivity of an opiate immunoassay for detecting hydrocodone and hydromorphone in urine from a clinical population: analysis of subthreshold results.

    Science.gov (United States)

    Bertholf, Roger L; Johannsen, Laura M; Reisfield, Gary M

    2015-01-01

    Urine drug testing (UDT) is an emerging standard of care in the evaluation and treatment of chronic non-cancer pain patients with opioid analgesics. UDT may be used both to verify adherence with the opioid analgesic regimen and to monitor abstinence from non-prescribed or illicit controlled substances. In the former scenario, it is vital to determine whether the drug is present in the urine, even at low concentrations, because failure to detect the drug may lead to accusations of opioid abuse or diversion. Opiate immunoassays typically are developed to detect morphine and are most sensitive to morphine and codeine. Although many opiate immunoassays also detect hydrocodone (HC) and/or hydromorphone (HM), sensitivities for these analytes are often much lower, increasing the possibility of negative screening results when the drug is present in the urine. We selected 112 urine specimens from patients who had been prescribed HC or hydromorphone but were presumptive negative by the Roche Online DAT Opiate II™ urine drug screening assay, which is calibrated to 300 ng/mL morphine. Using a GC/MS confirmatory method with a detection limit of 50 ng/mL both for HC and for HM, one or both of these opiates were detected in 81 (72.3%) of the urine specimens. Examination of the raw data from these presumptive negative opiate screens revealed that, in many cases, the turbidity signal was greater than the signal obtained for the negative control, but less than the signal for the 300 ng/mL (morphine) threshold calibrator. A receiver operating characteristic curve generated for the reciprocal of the ratio of turbidity measurements in the patient specimens and negative (drug-free) controls, against the presence or absence of HC and/or HM by confirmatory analyses, produced an area under the curve of 0.910. We conclude that this opiate immunoassay has sufficient sensitivity to detect HC and/or HM in some urine specimens that screen presumptive negative for these commonly prescribed

  9. Early versus late-phase consolidation of opiate reward memories requires distinct molecular and temporal mechanisms in the amygdala-prefrontal cortical pathway.

    Directory of Open Access Journals (Sweden)

    Shervin Gholizadeh

    Full Text Available The consolidation of newly acquired memories involves the temporal transition from a recent, less stable trace to a more permanent consolidated form. Opiates possess potent rewarding effects and produce powerful associative memories. The activation of these memories is associated with opiate abuse relapse phenomena and the persistence of compulsive opiate dependence. However, the neuronal, molecular and temporal mechanisms by which associative opiate reward memories are consolidated are not currently understood. We report that the consolidation of associative opiate reward memories involves a temporal and molecular switch between the basolateral nucleus of the amygdala (BLA (early consolidation phase to the medial prefrontal cortex (mPFC (late consolidation phase. We demonstrate at the molecular, behavioral and neuronal levels that the consolidation of a recently acquired opiate reward memory involves an extracellular signal-related kinase (ERK-dependent phosphorylation process within the BLA. In contrast, later-stage consolidation of a newly acquired memory is dependent upon a calcium-calmodulin-dependent (CaMKII, ERK-independent, mechanism in the mPFC, over a 12 hr temporal gradient. In addition, using in vivo multi-unit neuronal recordings in the mPFC, we report that protein synthesis within the BLA modulates the consolidation of opiate-reward memory in neuronal mPFC sub-populations, via the same temporal dynamic.

  10. Early versus late-phase consolidation of opiate reward memories requires distinct molecular and temporal mechanisms in the amygdala-prefrontal cortical pathway.

    Science.gov (United States)

    Gholizadeh, Shervin; Sun, Ninglei; De Jaeger, Xavier; Bechard, Melanie; Coolen, Lique; Laviolette, Steven R

    2013-01-01

    The consolidation of newly acquired memories involves the temporal transition from a recent, less stable trace to a more permanent consolidated form. Opiates possess potent rewarding effects and produce powerful associative memories. The activation of these memories is associated with opiate abuse relapse phenomena and the persistence of compulsive opiate dependence. However, the neuronal, molecular and temporal mechanisms by which associative opiate reward memories are consolidated are not currently understood. We report that the consolidation of associative opiate reward memories involves a temporal and molecular switch between the basolateral nucleus of the amygdala (BLA) (early consolidation phase) to the medial prefrontal cortex (mPFC) (late consolidation phase). We demonstrate at the molecular, behavioral and neuronal levels that the consolidation of a recently acquired opiate reward memory involves an extracellular signal-related kinase (ERK)-dependent phosphorylation process within the BLA. In contrast, later-stage consolidation of a newly acquired memory is dependent upon a calcium-calmodulin-dependent (CaMKII), ERK-independent, mechanism in the mPFC, over a 12 hr temporal gradient. In addition, using in vivo multi-unit neuronal recordings in the mPFC, we report that protein synthesis within the BLA modulates the consolidation of opiate-reward memory in neuronal mPFC sub-populations, via the same temporal dynamic.

  11. Molecular and Neuronal Plasticity Mechanisms in the Amygdala-Prefrontal Cortical Circuit: Implications for Opiate Addiction Memory Formation

    Directory of Open Access Journals (Sweden)

    Laura G Rosen

    2015-11-01

    Full Text Available The persistence of associative memories linked to the rewarding properties of drugs of abuse is a core underlying feature of the addiction process. Opiate class drugs in particular, possess potent euphorigenic effects which, when linked to environmental cues, can produce drug-related ‘trigger’ memories that may persist for lengthy periods of time, even during abstinence, in both humans and other animals. Furthermore, the transitional switch from the drug-naïve, non-dependent state to states of dependence and withdrawal, represents a critical boundary between distinct neuronal and molecular substrates associated with opiate-reward memory formation. Identifying the functional molecular and neuronal mechanisms related to the acquisition, consolidation, recall and extinction phases of opiate-related reward memories is critical for understanding, and potentially reversing, addiction-related memory plasticity characteristic of compulsive drug-seeking behaviors. The mammalian prefrontal cortex (PFC and basolateral nucleus of the amygdala (BLA share important functional and anatomical connections that are involved importantly in the processing of associative memories linked to drug reward. In addition, both regions share interconnections with the mesolimbic pathway’s ventral tegmental area (VTA and nucleus accumbens (NAc and can modulate dopamine (DA transmission and neuronal activity associated with drug-related DAergic signaling dynamics. In this review, we will summarize research from both human and animal modelling studies highlighting the importance of neuronal and molecular plasticity mechanisms within this circuitry during critical phases of opiate addiction-related learning and memory processing. Specifically, we will focus on two molecular signaling pathways known to be involved in both drug-related neuroadaptations and in memory-related plasticity mechanisms; the extracellular-signal-regulated kinase system (ERK and the Ca2+/calmodulin

  12. Molecular and neuronal plasticity mechanisms in the amygdala-prefrontal cortical circuit: implications for opiate addiction memory formation.

    Science.gov (United States)

    Rosen, Laura G; Sun, Ninglei; Rushlow, Walter; Laviolette, Steven R

    2015-01-01

    The persistence of associative memories linked to the rewarding properties of drugs of abuse is a core underlying feature of the addiction process. Opiate class drugs in particular, possess potent euphorigenic effects which, when linked to environmental cues, can produce drug-related "trigger" memories that may persist for lengthy periods of time, even during abstinence, in both humans, and other animals. Furthermore, the transitional switch from the drug-naïve, non-dependent state to states of dependence and withdrawal, represents a critical boundary between distinct neuronal and molecular substrates associated with opiate-reward memory formation. Identifying the functional molecular and neuronal mechanisms related to the acquisition, consolidation, recall, and extinction phases of opiate-related reward memories is critical for understanding, and potentially reversing, addiction-related memory plasticity characteristic of compulsive drug-seeking behaviors. The mammalian prefrontal cortex (PFC) and basolateral nucleus of the amygdala (BLA) share important functional and anatomical connections that are involved importantly in the processing of associative memories linked to drug reward. In addition, both regions share interconnections with the mesolimbic pathway's ventral tegmental area (VTA) and nucleus accumbens (NAc) and can modulate dopamine (DA) transmission and neuronal activity associated with drug-related DAergic signaling dynamics. In this review, we will summarize research from both human and animal modeling studies highlighting the importance of neuronal and molecular plasticity mechanisms within this circuitry during critical phases of opiate addiction-related learning and memory processing. Specifically, we will focus on two molecular signaling pathways known to be involved in both drug-related neuroadaptations and in memory-related plasticity mechanisms; the extracellular-signal-regulated kinase system (ERK) and the Ca(2+)/calmodulin-dependent protein

  13. Naloxone potentiates the inotropic effects of isoproterenol in vitro by a nonopiate receptor mechanism.

    Science.gov (United States)

    Lechner, R B

    1992-11-01

    Naloxone potentiates the effects of adrenergic agonists when administered to hypovolemic dogs, and it has been assumed that this effect is due to naloxone's action at opiate receptors. To help determine the site and mechanism of this interaction, we administered naloxone and its "d" stereo-isomer (which does not bind to opiate receptors) to guinea pig papillary muscles in the presence and absence of pharmacologic (isoproterenol) and physiologic (treppe) inotropic stimulation. In control muscles and in rapidly paced muscles, naloxone was without significant inotropic effect. In the presence of isoproterenol, d- and l-naloxone exerted significant positive inotropic effects that were dose dependent. We conclude that, since both d- and l-naloxone potentiated the inotropic effects of isoproterenol and this was seen in the absence of opioids, naloxone may increase contractility by a nonopiate receptor-mediated mechanism.

  14. Multimodal analgesia versus traditional opiate based analgesia after cardiac surgery, a randomized controlled trial

    DEFF Research Database (Denmark)

    Rafiq, Sulman; Steinbrüchel, Daniel Andreas; Wanscher, Michael Jaeger

    2014-01-01

    BACKGROUND: To evaluate if an opiate sparing multimodal regimen of dexamethasone, gabapentin, ibuprofen and paracetamol had better analgesic effect, less side effects and was safe compared to a traditional morphine and paracetamol regimen after cardiac surgery. METHODS: Open-label, prospective...... significantly lower average pain scores from the day of surgery throughout the third postoperative day. Extensive nausea and vomiting, was found in no patient in the multimodal group but in 13 patients in the morphine group, p ...-significant rise in the multimodal group, 33.0±53.4 vs. 19.9±48.5, p = 0.133. Patients in the multimodal group suffered less major in-hospital events in crude numbers: myocardial infarction (MI) (1 vs. 2, p = 0.54), stroke (0 vs. 3, p = 0.075), dialysis (1 vs. 2, p = 0.54), and gastrointestinal (GI) bleeding (0 vs...

  15. Disappearance of 6-acetylmorphine, morphine and codeine from human scalp hair after discontinuation of opiate abuse.

    Science.gov (United States)

    Shen, Min; Xiang, Ping; Sun, Yingying; Shen, Baohua

    2013-04-10

    Opiates continue to be used at high rates in East and Southeast Asia. Hair analysis for drugs of abuse has been developed into a powerful and widely used tool in forensic and clinical toxicology. Specifically, testing the proximal segment of scalp hair to confirm morphine (MOR) positive urine samples could solve the poppy seed problem. Human scalp hair grows approximately 1cm per month and can therefore reflect a retrospective timeline of drug exposure. This study is the first to investigate the disappearance of 6-acetylmorphine (6-AM), MOR and codeine (COD) from human scalp hair after the discontinuation of drug use. Thirty-two healthy women (ages 21-51 years) with a known history of heroin abuse, who went to a rehabilitation centre and ceased consuming heroin (for 4-5 months), were recruited into the study. A pharmacokinetic analysis in seven individual hair segments was performed using a first-order kinetic. Assuming a rate of hair growth of 1cm/month, the mean hair elimination half-lives of 6-AM, MOR and COD were 0.88 months (95% CI, 0.74-1.03), 0.73 months (95% CI, 0.64-0.81), and 0.61 months (95% CI, 0.54-0.69), respectively. Our results suggest that to evaluate the discontinuation of opiate abuse after a 6-month period of abstinence, the results from a 3-cm proximal hair segment should be free of 6-AM at the proposed 0.2 ng/mg cutoff level. This finding should become the basis for the interpretation of results from segmental hair analyses in the evaluation of drug abstinence.

  16. Separation of Opiate Isomers Using Electrospray Ionization and Paper Spray Coupled to High-Field Asymmetric Waveform Ion Mobility Spectrometry

    Science.gov (United States)

    Manicke, Nicholas E.; Belford, Michael

    2015-05-01

    One limitation in the growing field of ambient or direct analysis methods is reduced selectivity caused by the elimination of chromatographic separations prior to mass spectrometric analysis. We explored the use of high-field asymmetric waveform ion mobility spectrometry (FAIMS), an ambient pressure ion mobility technique, to separate the closely related opiate isomers of morphine, hydromorphone, and norcodeine. These isomers cannot be distinguished by tandem mass spectrometry. Separation prior to MS analysis is, therefore, required to distinguish these compounds, which are important in clinical chemistry and toxicology. FAIMS was coupled to a triple quadrupole mass spectrometer, and ionization was performed using either a pneumatically assisted heated electrospray ionization source (H-ESI) or paper spray, a direct analysis method that has been applied to the direct analysis of dried blood spots and other complex samples. We found that FAIMS was capable of separating the three opiate structural isomers using both H-ESI and paper spray as the ionization source.

  17. Economical synthesis of 13C-labeled opiates, cocaine derivatives and selected urinary metabolites by derivatization of the natural products.

    Science.gov (United States)

    Karlsen, Morten; Liu, Huiling; Johansen, Jon Eigill; Hoff, Bård Helge

    2015-03-25

    The illegal use of opiates and cocaine is a challenge world-wide, but some derivatives are also valuable pharmaceuticals. Reference samples of the active ingredients and their metabolites are needed both for controlling administration in the clinic and to detect drugs of abuse. Especially, (13)C-labeled compounds are useful for identification and quantification purposes by mass spectroscopic techniques, potentially increasing accuracy by minimizing ion alteration/suppression effects. Thus, the synthesis of [acetyl-(13)C4]heroin, [acetyl-(13)C4-methyl-(13)C]heroin, [acetyl-(13)C2-methyl-(13)C]6-acetylmorphine, [N-methyl-(13)C-O-metyl-(13)C]codeine and phenyl-(13)C6-labeled derivatives of cocaine, benzoylecgonine, norcocaine and cocaethylene was undertaken to provide such reference materials. The synthetic work has focused on identifying (13)C atom-efficient routes towards these derivatives. Therefore, the (13)C-labeled opiates and cocaine derivatives were made from the corresponding natural products.

  18. Exploring the Concepts of Abstinence and Recovery Through the Experiences of Long-Term Opiate Substitution Clients.

    Science.gov (United States)

    Notley, Caitlin; Blyth, Annie; Maskrey, Vivienne; Pinto, Hayley; Holland, Richard

    2015-01-01

    This study aimed to explore the client experience of long-term opiate substitution treatment (OST). A qualitative grounded theory study set in a U.K. rural community drug treatment service. Continuous OST enabled stability and a sense of "normality." Participants expressed relief at moving away from previous chaotic lifestyles and freedom from the persistent fear of opiate withdrawal. However, for some, being on a script made them feel withdrawn, lethargic, and unable to fully participate in mainstream society. Intrapersonal barriers (motivation and fear) were perceived as key barriers to abstinence. Participants experienced long-term OST as a transition between illicit drug use and recovery. Recovery was seen as a process rather than a fixed goal, confirming that there is a need for services to negotiate individualized recovery goals, spanning harm minimization and abstinence-oriented treatment approaches.

  19. Opioid Antagonists May Reverse Endogenous Opiate “Dependence” in the Treatment of Self-Injurious Behavior

    OpenAIRE

    Sandman, Curt A.; Aaron S. Kemp

    2011-01-01

    Self-injurious behavior (SIB) is a primary reason that individuals with neurodevelopmental disabilities (NDD) are either retained in restrictive environments or are administered psychotropic medication. There are no known causes and no universally accepted treatments for this complex behavior among individuals with NDD. There is developing evidence, however, that individuals exhibiting SIB have a disturbance of the opiate-mediated pain and pleasure system. One hypothesis is that SIB reflects ...

  20. Extraction of benzoylecgonine (cocaine metabolite) and opiates (codeine and morphine) from urine samples using the Zymark RapidTrace.

    Science.gov (United States)

    Diamond, F X; Vickery, W E; de Kanel, J

    1996-01-01

    The Zymark RapidTrace automated solid-phase extraction system has been evaluated for use in the urine drug-testing laboratory. Methods for cocaine metabolite (benzoylecgonine) and opiates (codeine and morphine) are described and evaluated. The linearity, precision, accuracy, recovery, and carryover statistics of these analytical protocols are presented. The advantages of extraction using the RapidTrace instead of solid-phase extraction with the manual vacuum manifold or liquid-liquid extraction methods are described.

  1. Adolescent opiate exposure in the female rat induces subtle alterations in maternal care and transgenerational effects on play behavior.

    Directory of Open Access Journals (Sweden)

    Nicole L. Johnson

    2011-06-01

    Full Text Available The non-medical use of prescription opiates, such as Vicodin® and MSContin®, has increased dramatically over the past decade. Of particular concern is the rising popularity of these drugs in adolescent female populations. Use during this critical developmental period could have significant long-term consequences for both the female user as well as potential effects on her future offspring. To address this issue, we have begun modeling adolescent opiate exposure in female rats and have observed significant transgenerational effects despite the fact that all drugs are withdrawn several weeks prior to pregnancy. The purpose of the current set of studies was to determine whether adolescent morphine exposure modifies postpartum care. In addition, we also examined juvenile play behavior in both male and female offspring. The choice of the social play paradigm was based on previous findings demonstrating effects of both postpartum care and opioid activity on play behavior. The findings revealed subtle modifications in the maternal behavior of adolescent morphine-exposed females, primarily related to the amount of time females’ spend nursing and in non-nursing contact with their young. In addition, male offspring of adolescent morphine-exposed mothers (MOR-F1 demonstrate decreased rough and tumble play behaviors, with no significant differences in general social behaviors (i.e. social grooming and social exploration. Moreover, there was a tendency toward increased rough and tumble play in MOR-F1 females, demonstrating the sex-specific nature of these effects. Given the importance of the postpartum environment on neurodevelopment, it is possible that modifications in maternal-offspring interactions, related to a history of adolescent opiate exposure, plays a role in the observed transgenerational effects. Overall, these studies indicate that the long-term consequences of adolescent opiate exposure can impact both the female and her future offspring.

  2. Efficiency of a combined peginterferon alpha-2a and ribavarin therapy in intravenous opiate substances abusers with chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    Jovanović Maja

    2009-01-01

    Full Text Available Background/Aim. The most important ethiology factor of chronic liver disease that progresses into terminal insufficiency is hepatitis C virus (HCV infection. Intravenous (iv drug abuse is the main cause for spreading HCV. Thus the therapy for such patients is of extreme importance in reducing the incidence of the disease. The aim of the study was to establish efficacy of a combined therapy with peginterferon alpha-2a and ribavirin in iv opiate substances abusers having chronic HCV infection in relation to sex, age, genotype and level of fibrosis and duration of HCV infection before the treatment. Methods. Thirty one iv opiate substances abusers with chronic hepatitis C (HHC were enrolled in the examination. The patients were divided according to the genotype into two groups. The patients with genotypes 1 and 4 (n = 18 were treated for 48 weeks, while those with genotypes 2 and 3 (n = 13 for 24 weeks. PCR HCV RNA, genotype determination and liver biopsy were done to each patient. Results. A stabile virological response was achieved in 93.5% of the patients, so the therapy demonstrated statistically significant efficacy i. v. opiate substances abusers with HHC (p < 0.001. There was no statistically significant difference in therapeutic response among patient groups formed according to the genotype, sex, duration of the disease and level of fibrosis (p > 0.05. Conclusion. Therapy of of iv opiate substances abusers with HHC has its specificities, and these patients need special treatment. Efficacy of the therapy was equivalent in patient groups formed according to the sex, genotype, level of fibrosis and duration of HCV infection. A combined therapy with peginterferon alfa 2a and ribavirin has high level of success in the treatment of these patients.

  3. Separation of opiate alkaloids by electrokinetic chromatography with sulfated-cyclodextrin as a pseudo-stationary phase.

    Science.gov (United States)

    Zakaria, Philip; Macka, Miroslav; Haddad, Paul R

    2003-01-24

    The separation of six related opiate alkaloids (morphine, thebaine, 10-hydroxythebaine, codeine, oripavine and laudanine) was studied using sulfated-cyclodextrin (s-CD) as a cation-exchange pseudo-stationary phase. Cation-exchange interactions between the cationic analytes and the anionic s-CD (7-11 mol of sulfate groups per mole CD) were found to bethe predominant mechanism, allowing the separations to be performed at low pH where the opiates are protonated and exhibit very similar mobilities. The concentrations of the s-CD and the competing ion (Na+ or Mg2+) in the electrolyte were used to govern the extent of the ion-exchange interactions. Interactions with the sulfated-cyclodextrin differed for each analyte, with oripavine exhibiting the strongest interaction and 10-thebaine and laudanine showing the weakest interactions. Despite the very similar structures of the analytes, these differences resulted in significant changes in separation selectivity. The separation was modelled using a migration equation derived from first principles and based on ion-exchange interactions between the s-CD and the opiates. Constants within the model were obtained by non-linear regression using a small subset of experimentally determined migration times. These constants related to the ion-exchange affinities of the s-CD for the various opiates. When the model was used to predict migration times under other experimental conditions, a very good correlation was obtained between observed and predicted mobilities (r2=0.996). Optimisation of the system was performed using the normalised resolution product and minimum resolution criteria and this process provided two optimised separations, each exhibiting a different separation selectivity.

  4. Prevalence and correlates of opiate overdose among young injection drug users in a large U.S. city.

    Science.gov (United States)

    Sherman, Susan G; Cheng, Yingkai; Kral, Alexander H

    2007-05-11

    The current study examines the prevalence and correlates of witnessing and experiencing opiate overdoses among a sample of young, injection drug users (IDUs) and non-injection drug users (NIDUs) in Baltimore, MD. Data were derived from a longitudinal study of 15-30 year old IDUs and NIDUs (N=309) who had initiated heroin, cocaine, and/or crack use within 5 years prior to study enrollment. Chi-square and Wilcoxon rank-sum tests were used in bivariate analyses of demographic and drug use variables with each of the two dependent variables. Multivariate logistic regression models were used to identify correlates of experiencing and witnessing overdose. Twenty-nine percent of participants reported having ever experienced an opiate overdose and 57% reported having ever witnessed an overdose. Having ever experienced an opiate overdose was independently associated with being White (Adjusted Odds Ratio [AOR]=3.2; 95% Confidence Interval [CI]: 1.6, 6.4) recent homelessness (AOR=2.9; 95%CI: 1.5, 5.7); and length of injection, 5.6-6.9 years versus 8 versus overdose was independently associated with being White (AOR=2.4; 95%CI: 1.4, 4.1) and injecting >8 years versus overdoses among young, newly initiated IDUs and NIDUs. The results could inform the growing number of overdose prevention efforts throughout the U.S.

  5. Effectiveness of Cognitive-Behavioral Group Therapy on Improving Quality of Life in Opiate Addicts under Methadone Maintenance Treatment

    Directory of Open Access Journals (Sweden)

    Fereshteh Momeni

    2013-04-01

    Full Text Available Objective: This study was aimed to assess the effectiveness of cognitive- behavioral group therapy on improvement of quality of life in opiate patients under methadone maintenance treatment. Method: This was a semi experimental study using control group also pre-test, post-test and follow-up. Thirty six patients on MMT were selected between the entire opiate addicts referred to Iranian national center for addiction studies within judgmental sampling and were randomly assigned into experimental and control groups. They were all administered the WHOQOL-BREF. In experimental group, cognitive behavior group therapy was performed in 8 sessions and the control group was registered in the waiting list for the CBGT. Findings: Data analysis revealed that the mean WHOQOL-BREF score in the experimental group had significant higher increase when compared with that of the control group. But it wasn’t significant in follow up. Conclusion: Results demonstrated the effectiveness of cognitive–behavior group therapy On improvement of quality of life of opiate addicts on MMT in short term but didn’t seem to be effective in long term.

  6. Simultaneous quantification of amphetamine, opiates, ketamine and relative metabolites in urine for confirmatory analysis by liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Lin, Huei-Ru; Choi, Ka-Ian; Lin, Tzu-Chieh; Hu, Anren

    2013-06-15

    The rise in amphetamine, ketamine and opiates abuse in Taiwan has created a need for a reliable confirmatory assay. A method that combines superficially porous liquid chromatography tandem mass spectrometry (LC-MS/MS) with solid-phase extraction (SPE) was developed for the simultaneous quantification of amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), ketamine, opiates, and their corresponding metabolites in urine. The total run time of the method was 6.7min including equilibration time. The method was validated in accordance with the European Commission (EC) Decision 2002/642/EC. The within- and between-day precision was below 13.6% and the accuracy ranged from -17.1% to +9.9% for all analytes. Ion suppression was observed but compensated by using deuterated internal standards. No carryover was detected and the analytes were stable at room temperature for 16h, and for 72h at 4°C, and three-thaw cycles. The method was further validated by comparison with a reference gas chromatography-mass spectrometry (GC-MS) method, using 52 authentic urine samples. The results indicated that for the target analytes studied, the LC-MS/MS analysis was as precise, accurate, and specific as the GC-MS method. In conclusion, the present LC-MS/MS method is robust and reliable, and suitable for use as a confirmation assay in the simultaneous urine drug testing and quantification of amphetamines, ketamines, and opiates.

  7. Morphofunctional alterations in ventral tegmental area dopamine neurons in acute and prolonged opiates withdrawal. A computational perspective.

    Science.gov (United States)

    Enrico, P; Migliore, M; Spiga, S; Mulas, G; Caboni, F; Diana, M

    2016-05-13

    Dopamine (DA) neurons of the ventral tegmental area (VTA) play a key role in the neurobiological basis of goal-directed behaviors and addiction. Morphine (MOR) withdrawal induces acute and long-term changes in the morphology and physiology of VTA DA cells, but the mechanisms underlying these modifications are poorly understood. Because of their predictive value, computational models are a powerful tool in neurobiological research, and are often used to gain further insights and deeper understanding on the molecular and physiological mechanisms underlying the development of various psychiatric disorders. Here we present a biophysical model of a DA VTA neuron based on 3D morphological reconstruction and electrophysiological data, showing how opiates withdrawal-driven morphological and electrophysiological changes could affect the firing rate and discharge pattern. The model findings suggest how and to what extent a change in the balance of GABA/GLU inputs can take into account the experimentally observed hypofunction of VTA DA neurons during acute and prolonged withdrawal, whereas morphological changes may play a role in the increased excitability of VTA DA cell to opiate administration observed during opiate withdrawal.

  8. Comparative Study of the Activity of Brain Behavioral Systems in Methamphetamine and Opiate Dependents

    Directory of Open Access Journals (Sweden)

    Alemikhah

    2016-01-01

    Full Text Available Background Substance dependency is a major problem for the general health of a society. Different approaches have investigated the substance dependency in order to explain it. Gray’s reinforcement sensitivity theory (RST is an advanced and important neuropsychological theory in this area. Objectives The aim of this study was to compare three systems of the revised reinforcement sensitivity theory the behavioral activation system (r-BAS, the revised behavioral inhibition system (r-BIS, and the revised fight/flight/freezing system (r-FFFS between patients dependent on methamphetamine and opiates, and a group of controls. Patients and Methods This research was a causal-comparative study that was conducted in the first six months of 2012. The population of the study was males of Mashhad city, who were dependent on methamphetamine or opiates, and ruling out psychotic disorders and prominent Axis II. Twenty-five people were selected by the convenient sampling method. Also, 25 non-dependent people from the patients’ relatives were selected and matched for the variables of age, gender, and education to participate in this study. Participants were evaluated using a structured clinical interview (SCID for DSM-IV, demographic questionnaire information, and a Jackson-5 questionnaire (2009. Data were analyzed by Chi-square, K-S, and independent t-test. Results The methamphetamine dependent group had a higher sensitivity in the r-BAS, r-BIS, and the r-Fight and r-Freezing systems compared to the control group (P 0.05. “The scores of r-BIS were also significantly higher in the methamphetamine-dependent group than the opioid-dependent and control groups. For the r-Fight variable, the methamphetamine-dependent group was higher than the opioid-dependent group”. Conclusions The personality patterns of patients dependent on methamphetamines were different from the controls. These people have a high sensitivity to punishment cues, such as being compared in

  9. Simultaneous determination of cocaine and opiates in dried blood spots by electrospray ionization tandem mass spectrometry.

    Science.gov (United States)

    Antelo-Domínguez, Ángel; Cocho, José Ángel; Tabernero, María Jesús; Bermejo, Ana María; Bermejo-Barrera, Pilar; Moreda-Piñeiro, Antonio

    2013-12-15

    A sample pre-treatment method based on blood spot collection filter cards was optimized as a means of using small volume samples for the screening and confirmation of cocaine and opiates abuse. Dried blood spots (DBSs) were prepared by dispersing 20 µL of whole blood specimens previously mixed with the internal standards (deuterated analogs of each target), and subjecting the whole DBS to extraction with 5 mL of methanol under orbital-horizontal shaking (180 rpm) for 10 min. Determinations were based on direct electrospray ionization tandem mass spectrometry (ESI-MS/MS) by injecting the re-dissolved methanol extract with the delivery solution (acetonitrile-water-formic acid, 80:19.875:0.125) at a flow rate of 60 µL min(-1), and using multiple reaction monitoring (MRM) mode with the m/z (precursor ion)→m/z (product ion) transitions for acquisition. Matrix effect has been found to be statistically significant (Multiple Range Test) when assessing cocaine, BZE, codeine and morphine, and the use of the standard addition method (dispersion of whole blood previously mixed with standards onto the filter papers) was needed for accurate determinations. The developed DBS-ESI-MS/MS procedure offered good intra-day and inter-day precisions (lower than 10% and 12%, respectively), as well as good intra-day and inter-day accuracies (inter-day absolute recoveries, expressed as the mean analytical recovery over three target concentration levels, of 103%, 100%, 101%, 98% and 100% for cocaine, BZE, codeine, morphine and 6-MAM, respectively). The high sensitivity inherent to MS/MS determinations combined with the minimal dilution of sample allowed low limits of quantification for all targets, and the developed method results therefore adequate for cocaine and opiates screening and confirmation purposes. The procedure was finally applied to DBSs prepared from whole blood from polydrug abusers, and results were compared with those obtained after a conventional sample pretreatment

  10. Pain management in total knee arthroplasty: efficacy of a multimodal opiate-free protocol

    Science.gov (United States)

    CANATA, GIAN LUIGI; CASALE, VALENTINA; CHIEY, ALFREDO

    2016-01-01

    Purpose this study was conducted to identify the most effective method of postoperative pain management, comparing the intravenous opiate infusion protocol with the use of a single periarticular local anesthetic infiltration (LAI) in patients undergoing total knee arthroplasty (TKA) surgery. Methods 50 patients submitted to TKA surgery between 2013 and 2015 were divided into two groups. Buprenorphine was administered intravenously to the patients in Group A, while the Group B patients received a single periarticular LAI (ropivacaine and ketorolac) during surgery. Pain was assessed using a visual analog scale (VAS) and the knee injury and osteoarthritis outcome score. Hemoglobin and hematocrit were measured in the early postoperative period and at 40 days post-surgery. Range of motion and inflammatory markers were also assessed. Statistical analysis was performed using Student’s t-test. Results student’s t-test showed no significant difference between the groups in functional outcomes or blood values, but a difference in VAS score on the day of surgery was found (p < 0.0001), in favor of Group B. Conclusions LAI considerably reduces postoperative pain, allowing rapid mobilization and accelerating functional recovery. Level of evidence Level I, prospective single-blind randomized trial. PMID:28217658

  11. Outcome of heroin-dependent adolescents presenting for opiate substitution treatment.

    LENUS (Irish Health Repository)

    Smyth, Bobby P

    2012-01-01

    Because the outcome of methadone and buprenorphine substitution treatment in adolescents is unclear, we completed a retrospective cohort study of 100 consecutive heroin-dependent adolescents who sought these treatments over an 8-year recruitment period. The participants\\' average age was 16.6 years, and 54 were female. Half of the patient group remained in treatment for over 1 year. Among those still in treatment at 12 months, 39% demonstrated abstinence from heroin. The final route of departure from the treatment program was via planned detox for 22%, dropout for 32%, and imprisonment for 8%. The remaining 39% were transferred elsewhere for ongoing opiate substitution treatment after a median period of 23 months of treatment. Males were more likely to exit via imprisonment (p < .05), but other outcomes were not predicted by gender. There were no deaths during treatment among these 100 patients who had a cumulative period of 129 person years at risk. Our findings suggest that this treatment delivers reductions in heroin use and that one fifth of patients will exit treatment following detox completion within a 1- to 2-year time frame.

  12. Influence of the histaminergic system on opiate-induced neurosecretion and behaviour.

    Science.gov (United States)

    Duka, T; Hoehe, M; Doenicke, A; Stephan, U; Matussek, N

    1987-01-01

    The influence of the histaminergic system on fentanyl (Fe)-induced growth hormone (GH) and prolactin (PRL) release as well as on Fe-induced increase of noradrenaline (NA) plasma levels has been studied in male volunteers. These volunteers received, according to a randomized block design, different pretreatments: the H1-antagonist dimethindene (Di) (0.1 mg/kg i.v.), or the H2-antagonist cimetidine (Ci)(5 mg/kg i.v.), or a combination of dimethindene and cimetidine (Di + Ci), or saline. The PRL increase caused by Fe (0.2 mg/70 kg) was not altered by pretreatment with the H1-antagonist Di, the H2-antagonist Ci, or the combination of both. The increase of NA plasma levels after Fe also was not modified by the histamine antagonists. In contrast, the maximum GH increase after Fe was blunted by the combination of Ci and Di, but not by either Ci or Di alone. These results suggest an involvement of the histaminergic system in opiate-induced GH-release.

  13. Synthesis and opiate activity of pseudo-tetrapeptides containing chiral piperazin-2-one and piperazine derivatives.

    Science.gov (United States)

    Yamashita, T; Tsuru, E; Banjyo, E; Doe, M; Shibata, K; Yasuda, M; Gemba, M

    1997-12-01

    Enantiomeric piperazin-2-one derivatives, N,N'-ethylene-bridged alanylphenylalanines (1a or 1b), were synthesized using (S)- or (R)-alanine and phenylalanine as starting materials, and were inserted into the second and third positions of enantiomeric pseudo-tetrapeptides (P1a- or P1b-OEt). The corresponding piperazine derivatives (1a- or 1b-sRed) obtained by selective BH3 reduction of the amide carbonyl groups of 1a or 1b were similarly inserted into the same positions of tetrapeptides (P1a- and P1b-sRed). Enantiomeric N,N'-ethylene-bridged tyrosyltyrosine derivatives (2a or 2b) obtained from (S)- or (R)-tyrosine were also inserted into the first and second positions of two pairs of enantiomeric tetrapeptides (P2a- and P2b-OEt or P'2a- and P'2b-OEt). The opiate activities of the eight peptides thus obtained were studied by use of the mouse vas deferens and the guinea pig ilcum assays in order to elucidate the structure-activity relationships of these peptides, especially with respect to stereochemistry.

  14. Historical review: Molecular and cellular mechanisms of opiate and cocaine addiction.

    Science.gov (United States)

    Nestler, Eric J

    2004-04-01

    The National Institute on Drug Abuse was founded in 1974, and since that time there have been significant advances in understanding the processes by which drugs of abuse cause addiction. The initial protein targets for almost all drugs of abuse are now known. Animal models that replicate key features of addiction are available, and these models have made it possible to characterize the brain regions that are important for addiction and other drug effects, such as physical dependence. A large number of drug-induced changes at the molecular and cellular levels have been identified in these brain areas and rapid progress is being made in relating individual changes to specific behavioral abnormalities in animal models of addiction. The current challenges are to translate this increasingly impressive knowledge of the basic neurobiology of addiction to human addicts, and to identify the specific genes that make some individuals either particularly vulnerable or resistant to addiction. In this article, I present a historical review of basic research on opiate and cocaine addiction.

  15. Degradation of Opioids and Opiates During Acid Hydrolysis Leads to Reduced Recovery Compared to Enzymatic Hydrolysis.

    Science.gov (United States)

    Sitasuwan, Pongkwan; Melendez, Cathleen; Marinova, Margarita; Mastrianni, Kaylee R; Darragh, Alicia; Ryan, Emily; Lee, L Andrew

    2016-10-01

    Drug monitoring laboratories utilize a hydrolysis process to liberate the opiates from their glucuronide conjugates to facilitate their detection by tandem mass spectrometry (MS). Both acid and enzyme hydrolysis have been reported as viable methods, with the former as a more effective process for recovering codeine-6-glucuronide and morphine-6-glucuronide. Here, we report concerns with acid-catalyzed hydrolysis of opioids, including a significant loss of analytes and conversions of oxycodone to oxymorphone, hydrocodone to hydromorphone and codeine to morphine. The acid-catalyzed reaction was monitored in neat water and patient urine samples by liquid chromatography-time-of-flight and tandem MS. These side reactions with acid hydrolysis may limit accurate quantitation due to loss of analytes, possibly lead to false positives, and poorly correlate with pharmacogenetic profiles, as cytochrome P450 enzyme (CYP2D6) is often involved with oxycodone to oxymorphone, hydrocodone to hydromorphone and codeine to morphine conversions. Enzymatic hydrolysis process using the purified, genetically engineered β-glucuronidase (IMCSzyme(®)) addresses many of these concerns and demonstrates accurate quantitation and high recoveries for oxycodone, hydrocodone, oxymorphone and hydromorphone.

  16. Distribution of opiates in femoral blood and vitreous humour in heroin/morphine-related deaths.

    Science.gov (United States)

    Rees, Kelly A; Pounder, Derrick J; Osselton, M David

    2013-03-10

    The distribution of free morphine (FM), codeine and 6-acetylmorphine (6AM) in vitreous humour (VH) and femoral blood (FB) was measured in 70 cases involving heroin/morphine. The relationship between tissue drug concentrations was assessed with respect to case circumstances. Total morphine (TM) concentrations in FB are also reported. The relative concentrations of FM in VH and FB were influenced by survival time. In rapid deaths (3h; n=12) the VH concentration (median 0.15 mg/L) was higher than in FB (0.092 mg/L; p>.05). Free morphine VH/FB ratios were significantly higher in delayed (median 1.3) compared to rapid deaths (0.64). Although these findings indicate a lag in the distribution of morphine into the VH, overlaps were observed in the VH/FB ratio in rapid and delayed death groups which limits the interpretive use of VH/FB ratios. Codeine and 6AM appeared to distribute more rapidly into the VH. Despite the observation that all opiate analytes were correlated between FB and VH (r ≥ 61; p<.01), our results indicate that in the absence of a blood sample, blood concentrations cannot be reliably inferred from that measured in the VH. In the absence of additional toxicological evidence, the use of FM to TM ratios in blood as an indicator of survival time is not advised.

  17. Harm reduction for injecting opiate users: an update and implications in China

    Institute of Scientific and Technical Information of China (English)

    Ma-ja MEISE; Xi WANG; Marie-Luise SAUTER; Yan-ping BAO; Jie SHI; Zhi-min LIU; Lin LU

    2009-01-01

    The harm associated with high-risk injected opiate use and the threat of the HIV epidemic among injecting drug users has become a worldwide problem. Twenty years ago, in the face of a rapid increase in mortality rates among injecting drug users and the upcoming threat of HW, the first harm-reduction programs were implemented in the Western world. This paper is a literature review describing four forms of harm reduction currently in use in Europe, North America, and Australia. Each represents a reasonable counterapproach to the threat of increased prevalence of HIV among injecting drug users in transitional and developing countries. The paper attempts to explain the concepts behind the most commonly used types of harm reduction and provides a brief overview of the advantages and disadvantages of each and the reasons for their implementation. The main focus of the review is on the definition and the practical aspects of harm reduction; it includes a brief introduction of Chinese harm-reduction efforts and their implications.

  18. Toxicological Analysis of Opiates from Alternative Matrices Collected from an Exhumed Body.

    Science.gov (United States)

    Cippitelli, Marta; Mirtella, Dora; Ottaviani, Giovanni; Tassoni, Giovanna; Froldi, Rino; Cingolani, Mariano

    2017-05-18

    In this case study, the body of a 45-year-old man was exhumed after 1 year at the request of the public prosecutor to assess whether the death was caused by drug consumption. Toxicological analyses were performed on several matrices, including liver, kidney, and the alternative matrices hair and teeth. The systematic toxicological analysis (STA), which consisted of basic and acid liquid/liquid extraction and gas chromatography-mass spectrometry (GC-MS) analysis, showed the presence of opiates in each of the matrices analyzed. Subsequently, to confirm and quantify the presence of opioids, samples of each of the matrices were subjected to solid-phase extraction and specific GC-MS analysis. The case presented demonstrates the possibility of drug detection in an exhumed body that has been buried for 1 year, despite the problems of quantitative interpretation of the data, and that toxicological results could be useful along with other forensic evidence. © 2017 American Academy of Forensic Sciences.

  19. Opiates Upregulate Adhesion Molecule Expression in Brain MicroVascular Endothelial Cells (BMVEC: Implications for Altered Blood Brain Barrier (BBB Permeability

    Directory of Open Access Journals (Sweden)

    Madhavan P.N. Nair

    2006-01-01

    Full Text Available The blood-brain barrier (BBB is an intricate cellular system composed of vascular endothelial cells and perivascular astrocytes that restrict the passage of immunocompetent cells into the central nervous system (CNS. Expression of the adhesion molecules, intercellular adhesion molecule 1 (ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1 on brain microvascular endothelial cells (BMVEC and their interaction with human immunodeficiency virus (HIV-1 viral proteins may help enhance viral adhesion and virus-cell fusion resulting in increased infectivity. Additionally, transmigration through the BBB is facilitated by both endothelial and monocyte/macrophage-derived nitric oxide (NO. Dysregulated production of NO by BMVEC due to opiates and HIV-1 viral protein interactions play a pivotal role in brain endothelial injury, resulting in the irreversible loss of BBB integrity, which may lead to enhanced infiltration of virus-carrying cells across the BBB. Opioids act as co-factors in the neuropathogenesis of HIV-1 by facilitating BBB dysfunction however, no studies have been done to investigate the role of opiates alone or in combination with HIV-1 viral proteins on adhesion molecule expression in BMVEC. We hypothesize that opiates such as heroin and morphine in conjunction with the HIV-1 viral protein gp120 increase the expression of adhesion molecules ICAM-1 and VCAM-1 and these effects are mediated via the modulation of NO. Results show that opiates alone and in synergy with gp120 increase both the genotypic and phenotypic expression of ICAM-1 and VCAM-1 by BMVEC, additionally, these opiate induced effects may be the result of increased NO production. These studies will provide a better understanding of how opiate abuse in conjunction with HIV-1 infection facilitates the breakdown of the BBB and exacerbates the neuropathogenesis of HIV-1. Elucidation of the mechanisms of BBB modulation will provide new therapeutic approaches to maintain BBB integrity

  20. Characterization of rat spinal cord receptors to FLFQPQRFamide, a mammalian morphine modulating peptide: a binding study.

    Science.gov (United States)

    Allard, M; Geoffre, S; Legendre, P; Vincent, J D; Simonnet, G

    1989-10-23

    An in vitro binding assay, using 125I-YLFQPQRFamide, a newly synthetized iodinated analog of FLFQPQRFamide, in which Phe1 (F) has been substituted by a Tyr (Y), was developed to demonstrate and characterize putative binding sites of this brain morphine modulating peptide. This radioligand bound in a time-dependent manner to rat spinal cord membrane preparation. This binding was dose-dependent, saturable and reversible. Both kinetic data and saturation measured at equilibrium lead to the existence of a homogenous population of high affinity binding sites with a Kd value of 0.09-0.1 nM and a maximal capacity Bmax of 14.5 +/- 2 fmol/mg protein. Results of competition experiments show that both FLFQPQRFamide and its analog YLFQPQRFamide had a similar capacity to inhibit the 125I-YLFQPQRFamide binding, suggesting that this radioiodinated analog is a good tool to study binding characteristics of FLFQPQRFamide receptors. The related octadecapeptide AGEGLSSPFWSLAAPQRFamide, another mammalian morphine modulating peptide competes for radioligand binding with similar potency. Our results also show that mu, delta and kappa opiate receptor agonists as well as the antagonist naloxone were not able to affect binding either in presence or in absence of 120 mM NaCl. Together, these data demonstrate that FLFQPQRFamide does not function as an endogenous opiate receptor antagonist and that is capacity to reduce opiate-induced analgesia is supported by specific binding sites.

  1. Escalating morphine exposures followed by withdrawal in feline immunodeficiency virus-infected cats: a model for HIV infection in chronic opiate abusers.

    Science.gov (United States)

    Barr, Margaret C; Huitron-Resendiz, Salvador; Sanchez-Alavez, Manuel; Henriksen, Steven J; Phillips, Tom R

    2003-11-24

    Opiate abuse is a risk factor for human immunodeficiency virus (HIV) infection. Because the direct effects of opiates on HIV infection are difficult to determine epidemiologically, animal models of lentivirus infection are relied upon to study the effects of opiates in the absence of confounding factors. Morphine, the predominant metabolite of heroin, is used in most experimental systems examining heroin abuse. In this study, morphine treatment of feline immunodeficiency virus (FIV)-infected cats modeled a typical pattern of escalating drug use interspersed with withdrawals. Plasma cortisol levels were measured for evidence of stress associated with morphine withdrawal. In the morphine-treated cats, cortisol levels peaked at time points corresponding to morphine withdrawal and returned to baseline levels during treatment and several weeks after the final withdrawal. Morphine-treated cats displayed clear behavioral and physical signs of opiate exposure and evidence of withdrawal when the drug was stopped. Morphine-exposed cats did not experience enhanced severity of FIV-related disease; in fact, morphine demonstrated a protective effect on FIV-associated changes in brainstem auditory evoked potentials. Our research suggests that opiate exposure is unlikely to adversely affect the progression of acute lentivirus infection and might be beneficial in controlling associated neurological disease.

  2. Different Levels in Orexin Concentrations and Risk Factors Associated with Higher Orexin Levels: Comparison between Detoxified Opiate and Methamphetamine Addicts in 5 Chinese Cities

    Directory of Open Access Journals (Sweden)

    Haoran Zhang

    2013-01-01

    Full Text Available This study sought to explore the degree of orexin levels in Chinese opiate and methamphetamine addicts and the differences between them. The cross-sectional study was conducted among detoxified drug addicts from Mandatory Detoxification Center (MDC in five Chinese cities. Orexin levels were assayed with radioimmunoassay (RIA. Mann-Whitney U test and Kruskal-Wallis test were used to detect differences across groups, and logistic regression was used to explore the association between orexin levels and characteristics of demographic and drug abuse. Between November 2009 and January 2011, 285 opiates addicts, 112 methamphetamine addicts, and 79 healthy controls were enrolled. At drug withdrawal period, both opiate and methamphetamine addicts had lower median orexin levels than controls, and median orexin levels in opiate addicts were higher than those in methamphetamine addicts (all above P<0.05. Adjusted odds of the above median concentration of orexin were higher for injection than “chasing the dragon” (AOR = 3.1, 95% CI = 1.2–7.9. No significant factors associated with orexin levels of methamphetamine addicts were found. Development of intervention method on orexin system by different administration routes especially for injected opiate addicts at detoxification phase may be significant and was welcome.

  3. Therapeutical Neurotargeting via Magnetic Nanocarrier: Implications to Opiate-Induced Neuropathogenesis and NeuroAIDS.

    Science.gov (United States)

    Sagar, Vidya; Pilakka-Kanthikeel, Sudheesh; Atluri, Venkata S R; Ding, Hong; Arias, Adriana Y; Jayant, Rahul D; Kaushik, Ajeet; Nair, Madhavan

    2015-10-01

    Magnetite (Fe3O4) is the most commonly and extensively explored magnetic nanoparticles (MNPs) for drug-targeting and imaging in the field of biomedicine. Nevertheless, its potential application as safe and effective drug-carrier for CNS (Central Nervous System) anomalies is very limited. Previous studies have shown an entangled epidemic of opioid use and HIV infection and increased neuropathogenesis. Opiate such as morphine, heroine, etc. are used frequently as recreational drugs. Existing treatments to alleviate the action of opioid are less effective at CNS level due to impermeability of therapeutic molecules across brain barriers. Thus, development of an advanced nanomedicine based approach may pave the way for better treatment strategies. We herein report magnetic nanoformulation of a highly selective and potent morphine antagonist, CTOP (D-Pen-Cys-Tyr-DTrp-Orn-Thr-Pen-Thr-NH2), which is impenetrable to the brain. MNPs, synthesized in size range from 25 to 40 nm, were characterized by Transmission electron microscopy and assembly of MNPs-CTOP nanoformulations were confirmed by FTIR spectroscopy and fluorescent detection. Flow-cytometry analysis showed that biological efficacy of this nanoformulation in prevention of morphine induced apoptosis in peripheral blood mononuclear cells remains equivalent to that of free CTOP. Similarly, confocal microscopy reveals comparable efficacy of free and MNPs bound CTOP in protecting modulation of neuronal dendrite and spine morphology during morphine exposure and morphine-treated HIV infection. Further, typical transmigration assay showed increased translocation of MNPs across in vitro blood-brain barrier upon exposure of external magnetic force where barrier integrity remains unaltered. Thus, the developed nanoformulation could be effective in targeting brain by application of external magnetic force to treat morphine addiction in HIV patients.

  4. The paradox of control: An ethnographic analysis of opiate maintenance treatment in a Norwegian prison.

    Science.gov (United States)

    Mjåland, Kristian

    2015-08-01

    Opiate maintenance treatment (OMT) is increasingly being offered in prisons throughout Europe. The benefits of OMT in prison have been found to be similar to those produced by OMT in community settings. However, prison-based OMT has been a controversial issue because of fear of the diversion of OMT medications and the development of black markets for prescription drugs such as buprenorphine and methadone. Prison-based OMT thus involves a delicate balance between the considerations of control and treatment. This article reports on an ethnographic study of a prison-based OMT programme in a closed Norwegian prison. The data include field notes from eight months of participant observation in the prison as well as qualitative interviews with 23 prisoners and 12 prison staff. Midway through the fieldwork, the prison authorities established a separate unit for OMT-enrolled prisoners to reduce the widespread diversion of buprenorphine. This "natural experiment" is explored in the analysis. The prison-based OMT programme was characterised by strict and repressive control to prevent the diversion of buprenorphine, and the control became even stricter after the establishment of the OMT unit. However, the diversion of buprenorphine increased rather than decreased after the establishment of the OMT unit. To understand this "paradox of control", the article engages with theories of legitimacy, power and resistance. The excessive and repressive control was perceived as illegitimate and unfair by the majority of study participants. In various ways, many prisoners protested, confronted and subverted the OMT programme. The increase in buprenorphine diversion is interpreted as a form of collective resistance towards the perceived unfairness of the OMT programme. The article demonstrates that an unbalanced and control-dominated approach to prison-based OMT may have the opposite effect of what is intended. Copyright © 2015 The Author. Published by Elsevier B.V. All rights reserved.

  5. Machine-learning identifies substance-specific behavioral markers for opiate and stimulant dependence.

    Science.gov (United States)

    Ahn, Woo-Young; Vassileva, Jasmin

    2016-04-01

    Recent animal and human studies reveal distinct cognitive and neurobiological differences between opiate and stimulant addictions; however, our understanding of the common and specific effects of these two classes of drugs remains limited due to the high rates of polysubstance-dependence among drug users. The goal of the current study was to identify multivariate substance-specific markers classifying heroin dependence (HD) and amphetamine dependence (AD), by using machine-learning approaches. Participants included 39 amphetamine mono-dependent, 44 heroin mono-dependent, 58 polysubstance dependent, and 81 non-substance dependent individuals. The majority of substance dependent participants were in protracted abstinence. We used demographic, personality (trait impulsivity, trait psychopathy, aggression, sensation seeking), psychiatric (attention deficit hyperactivity disorder, conduct disorder, antisocial personality disorder, psychopathy, anxiety, depression), and neurocognitive impulsivity measures (Delay Discounting, Go/No-Go, Stop Signal, Immediate Memory, Balloon Analogue Risk, Cambridge Gambling, and Iowa Gambling tasks) as predictors in a machine-learning algorithm. The machine-learning approach revealed substance-specific multivariate profiles that classified HD and AD in new samples with high degree of accuracy. Out of 54 predictors, psychopathy was the only classifier common to both types of addiction. Important dissociations emerged between factors classifying HD and AD, which often showed opposite patterns among individuals with HD and AD. These results suggest that different mechanisms may underlie HD and AD, challenging the unitary account of drug addiction. This line of work may shed light on the development of standardized and cost-efficient clinical diagnostic tests and facilitate the development of individualized prevention and intervention programs for HD and AD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Validation of analysis of amphetamines, opiates, phencyclidine, cocaine, and benzoylecgonine in oral fluids by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Kala, Subbarao V; Harris, Steve E; Freijo, Tom D; Gerlich, Stan

    2008-10-01

    The aim of the present study was to develop and validate a method for the detection and quantitation of drugs of abuse in oral fluids. Fortified oral fluid samples (made in-house) and samples from donors collected with Quantasil oral fluid collection kits from Immunalysis were screened on an Olympus 5400 using reagents purchased from Immunalysis. Amphetamines (AMPs), opiates, phencyclidine (PCP), and cocaine and its metabolite benzoylecgonine (BE) in oral fluids were quantitated by an Applied Biosystems 3200 QTRAP liquid chromatograph-tandem mass spectrometer (LC-MS-MS). AMPs, opiates, PCP, cocaine, and BE were extracted from samples using liquid-liquid or solid-phase extractions and the extracts were separated on a Shimadzu high-performance liquid chromatograph prior to the MS-MS analysis. For each drug, two multiple reaction mode transitions were monitored using positive electrospray ionization coupled to an MS-MS detector. Corresponding d3, d5, d6, and d11 internal standards were used to quantitate the results. The limit of detection/quantitation for AMPs, opiates, PCP, cocaine, and its metabolite BE were 10, 10, 2, 2, and 2 ng/mL of oral fluid, respectively, on a signal-to-noise ratio > 4. This corresponded to 25, 25, 5, 5, and 5 pg on column. The method was verified by participating in the North America Oral Fluid Proficiency Testing administered by Research Triangle Institute and by analyzing real samples from donors. In conclusion, LC-MS-MS provided a simple way to analyze and quantitate drugs of abuse in oral fluids.

  7. Alcohol-related brief intervention in patients treated for opiate or cocaine dependence: a randomized controlled study

    Directory of Open Access Journals (Sweden)

    Khan Riaz

    2011-08-01

    Full Text Available Abstract Background Despite the importance of heavy drinking and alcohol dependence among patients with opiate and cocaine dependence, few studies have evaluated specific interventions within this group. The aim of the present study was to evaluate the impact of screening with the Alcohol Use Disorders Identification Test (AUDIT and of brief intervention (BI on alcohol use in a sample of patients treated for opioid or cocaine dependence in a specialized outpatient clinic. Methods Adult outpatients treated for opioid or cocaine dependence in Switzerland were screened for excessive alcohol drinking and dependence with the AUDIT. Patients with AUDIT scores that indicated excessive drinking or dependence were randomized into two groups--treatment as usual or treatment as usual together with BI--and assessed at 3 months and 9 months. Results Findings revealed a high rate (44% of problematic alcohol use (excessive drinking and dependence among patients with opiate and cocaine dependence. The number of drinks per week decreased significantly between T0 (inclusion and T3 (month 3. A decrease in average AUDIT scores was observed between T0 and T3 and between T0 and T9 (month 9. No statistically significant difference between treatment groups was observed. Conclusions In a substance abuse specialized setting, screening for alcohol use with the AUDIT, followed by feedback on the score, and use of alcohol BI are both possibly useful strategies to induce changes in problematic alcohol use. Definitive conclusions cannot, however, be drawn from the study because of limitations such as lack of a naturalistic group. An important result of the study is the excellent internal consistency of AUDIT in a population treated for opiate or cocaine dependence.

  8. HIV-1 alters neural and glial progenitor cell dynamics in the central nervous system: coordinated response to opiates during maturation.

    Science.gov (United States)

    Hahn, Yun Kyung; Podhaizer, Elizabeth M; Hauser, Kurt F; Knapp, Pamela E

    2012-12-01

    HIV-associated neurocognitive disorders (HANDs) are common sequelae of human immunodeficiency virus (HIV) infection, even when viral titers are well controlled by antiretroviral therapy. Evidence in patients and animal models suggests that neurologic deficits are increased during chronic opiate exposure. We have hypothesized that central nervous system (CNS) progenitor cells in both adult and developing CNS are affected by HIV infection and that opiates exacerbate these effects. To examine this question, neural progenitors were exposed to HIV-1 Tat(1-86) in the developing brain of inducible transgenic mice and in vitro. We examined whether Tat affected the proliferation or balance of progenitor populations expressing nestin, Sox2, and Olig2. Disease relevance was further tested by exposing human-derived progenitors to supernatant from HIV-1 infected monocytes. Studies concentrated on striatum, a region preferentially targeted by HIV and opiates. Results were similar among experimental paradigms. Tat or HIV exposure reduced the proliferation of undifferentiated (Sox2(+)) progenitors and oligodendroglial (Olig2(+)) progenitors. Coexposure to morphine exacerbated the effects of Tat or HIV-1(SF162) supernatant, but partially reversed HIV-1(IIIB) supernatant effects. Populations of Sox2(+) and Olig2(+) cells were also reduced by Tat exposure, although progenitor survival was unaffected. In rare instances, p24 immunolabeling was detected in viable human progenitors by confocal imaging. The vulnerability of progenitors is likely to distort the dynamic balance among neuron/glial populations as the brain matures, perhaps contributing to reports that neurologic disease is especially prevalent in pediatric HIV patients. Pediatric disease is atypical in developed regions but remains a serious concern in resource-limited areas where infection occurs commonly at birth and through breast feeding.

  9. Opiate sensitization induces FosB/ΔFosB expression in prefrontal cortical, striatal and amygdala brain regions.

    Directory of Open Access Journals (Sweden)

    Gary B Kaplan

    Full Text Available Sensitization to the effects of drugs of abuse and associated stimuli contributes to drug craving, compulsive drug use, and relapse in addiction. Repeated opiate exposure produces behavioral sensitization that is hypothesized to result from neural plasticity in specific limbic, striatal and cortical systems. ΔFosB and FosB are members of the Fos family of transcription factors that are implicated in neural plasticity in addiction. This study examined the effects of intermittent morphine treatment, associated with motor sensitization, on FosB/ΔFosB levels using quantitative immunohistochemistry. Motor sensitization was tested in C57BL/6 mice that received six intermittent pre-treatments (on days 1, 3, 5, 8, 10, 12 with either subcutaneous morphine (10 mg/kg or saline followed by a challenge injection of morphine or saline on day 16. Mice receiving repeated morphine injections demonstrated significant increases in locomotor activity on days 8, 10, and 12 of treatment (vs. day 1, consistent with development of locomotor sensitization. A morphine challenge on day 16 significantly increased locomotor activity of saline pre-treated mice and produced even larger increases in motor activity in the morphine pre-treated mice, consistent with the expression of opiate sensitization. Intermittent morphine pre-treatment on these six pre-treatment days produced a significant induction of FosB/ΔFosB, measured on day 16, in multiple brain regions including prelimbic (PL and infralimbic (IL cortex, nucleus accumbens (NAc core, dorsomedial caudate-putamen (CPU, basolateral amygdala (BLA and central nucleus of the amygdala (CNA but not in a motor cortex control region. Opiate induced sensitization may develop via Fos/ΔFosB plasticity in motivational pathways (NAc, motor outputs (CPU, and associative learning (PL, IL, BLA and stress pathways (CNA.

  10. [The therapeutic alliance as a main factor of building cooperation during the treatment of patients with opiate addiction].

    Science.gov (United States)

    Agibalova, T V; Tuchin, P V; Shustov, D I; Buzik, O Zh

    2014-01-01

    Objective. To assess an alliance-centred method of short-term psychotherapy (AP) in the formation of compliance in patients with opiate addiction. Material and methods. Authors studied 100 male inpatients with ICD-10 diagnosis Opioid Dependence (F11.2). Patients were stratified into main (with use of AP) and control groups. The tasks of short-term psychotherapy were to determine mutual goals for the patient and the physician and the interaction between them. Results and Conclusion. Based on some special quantitative psychological tests and correlation analysis, it was identified that AP stimulated compliance behaviour in patients with opioid dependence more effectively than traditional recommendations.

  11. Rapid analysis of urinary opiates using fast gas chromatography–mass spectrometry and hydrogen as a carrier gas

    OpenAIRE

    Sumandeep Rana; Rakesh K. Garg; Anu Singla

    2014-01-01

    A sensitive and specific fast gas chromatography–mass spectrometry (FGC–MS) analytical method using hydrogen as a carrier gas is developed for the rapid simultaneous determination of morphine, codeine, hydrocodone and hydromorphone in human urine. Urine samples were spiked with deuterated internal standards, morphine-d3, codeine-d3, hydrocodone-d3 and hydro-morphone-d3, subjected to acid hydrolysis, treated with hydroxylamine to convert the keto-opiates to oximes and then extracted using a po...

  12. Buprenorphine-induced antinociception is mediated by mu-opioid receptors and compromised by concomitant activation of opioid receptor-like receptors.

    Science.gov (United States)

    Lutfy, Kabirullah; Eitan, Shoshana; Bryant, Camron D; Yang, Yu C; Saliminejad, Nazli; Walwyn, Wendy; Kieffer, Brigitte L; Takeshima, Hiroshi; Carroll, F Ivy; Maidment, Nigel T; Evans, Christopher J

    2003-11-12

    Buprenorphine is a mixed opioid receptor agonist-antagonist used clinically for maintenance therapy in opiate addicts and pain management. Dose-response curves for buprenorphine-induced antinociception display ceiling effects or are bell shaped, which have been attributed to the partial agonist activity of buprenorphine at opioid receptors. Recently, buprenorphine has been shown to activate opioid receptor-like (ORL-1) receptors, also known as OP4 receptors. Here we demonstrate that buprenorphine, but not morphine, activates mitogen-activated protein kinase and Akt via ORL-1 receptors. Because the ORL-1 receptor agonist orphanin FQ/nociceptin blocks opioid-induced antinociception, we tested the hypothesis that buprenorphine-induced antinociception might be compromised by concomitant activation of ORL-1 receptors. In support of this hypothesis, the antinociceptive effect of buprenorphine, but not morphine, was markedly enhanced in mice lacking ORL-1 receptors using the tail-flick assay. Additional support for a modulatory role for ORL-1 receptors in buprenorphine-induced antinociception was that coadministration of J-113397, an ORL-1 receptor antagonist, enhanced the antinociceptive efficacy of buprenorphine in wild-type mice but not in mice lacking ORL-1 receptors. The ORL-1 antagonist also eliminated the bell-shaped dose-response curve for buprenorphine-induced antinociception in wild-type mice. Although buprenorphine has been shown to interact with multiple opioid receptors, mice lacking micro-opioid receptors failed to exhibit antinociception after buprenorphine administration. Our results indicate that the antinociceptive effect of buprenorphine in mice is micro-opioid receptor-mediated yet severely compromised by concomitant activation of ORL-1 receptors.

  13. Sequential pattern of non-medical drug use in the drug career of opiate dependents in Nagpur, India.

    Science.gov (United States)

    Wairagkar, N S; Wahab, S N; Kulkarni, H R

    1996-12-01

    A study was carried out in a group of opiate addicts who reported to various centers in Nagpur city, India, to know the sequential pattern of nonmedical drug use in the drug career of opiate dependents in Nagpur. The mean age of the study group was 28.2 years, the majority were males, educated up to 10th standard, employed in various occupations like petty business, vehicle driving, etc, with an average monthly income of Rs. 316. The average number of drugs ever used per person was 3.7 +/- 1.2, those recently used was 2.6 +/- 0.9 and currently used was 2.2 +/- 0.6. The study group experienced 13 drug types in their addict careers. Beedi¿cigarette was the first drug abused by the majority. Drug careers starting with beedi¿cigarette, progressing to alcohol and then to canabis and finally to heroin were observed in a majority of subjects. There appeared to be a shift from multidrug use to the singular combination of heroin and beedi¿cigarette currently. Use of all other drugs declined in favor of heroin as the career progressed. The study indicates that preventive programs should be directed at reducing the use of initial drugs like beedi¿cigarette and alcohol and also reducing the social acceptability of these drugs as measure for preventing progression to hard drugs like heroin.

  14. The Effectiveness of Methadone Maintenance Therapy Among Opiate - Dependants Registered with Hospital Raja Perempuan Zainab II Kota Bharu, Kelantan.

    Science.gov (United States)

    Premila Devi, Jeganathan; Azriani, Ab Rahman; Zahiruddin, Wan Mohd; Mohd Ariff, Mohd Noor; Noor Hashimah, Abdullah

    2012-10-01

    The objective of this study was to determine the effectiveness of MMT program among injecting drug users (IDUs) in Kota Bharu, Kelantan. The study was a retrospective study based on the records of injecting drug users (IDUs) involved in the MMT program from November 2005 to 31st Jan 2008, registered at the Psychiatric Clinic of Hospital Raja Perempuan Zainab II. Opiate Treatment Index (OTI) was used as the research instrument. Repeated measures ANCOVA was used to compare the mean scores during the entry period and after completing twelve months of MMT program after adjusted for age, marital status, and level of education. A total of 117 file records were reviewed. There was significant reduction in the mean scores after 12 months of heroin Q score, HIV Risk-taking Behavior Scale and health scale after adjusted for age, marital status, and level of education. For Heroin Q score, mean difference was 2.01 (95% CI: 1.45, 2.56), for HIV Risk-taking Behavior Scale, mean difference was 7.64 (95% CI: 6.03, 9.26), and for health scale, mean difference was 5.35(95% CI: 3.90, 6.79). This study supports the evidence that MMT program is effective in treating heroin and opiate dependence.

  15. A common molecular motif characterizes extracellular allosteric enhancers of GPCR aminergic receptors and suggests enhancer mechanism of action.

    Science.gov (United States)

    Root-Bernstein, Robert; Dillon, Patrick F

    2014-01-01

    Several classes of compounds that have no intrinsic activity on aminergic systems nonetheless enhance the potency of aminergic receptor ligands three-fold or more while significantly increasing their duration of activity, preventing tachyphylaxis and reversing fade. Enhancer compounds include ascorbic acid, ethylenediaminetetraacetic acid, corticosteroids, opioid peptides, opiates and opiate antagonists. This paper provides the first review of aminergic enhancement, demonstrating that all enhancers have a common, inobvious molecular motif and work through a common mechanism that is manifested by three common characteristics. First, aminergic enhancers bind directly to the amines they enhance, suggesting that the common structural motif is reflected in common binding targets. Second, one common target is the first extracellular loop of aminergic receptors. Third, at least some enhancers are antiphosphodiesterases. These observations suggest that aminergic enhancers act on the extracellular surface of aminergic receptors to keep the receptor in its high affinity state, trapping the ligand inside the receptor. Enhancer binding produces allosteric modifications of the receptor structure that interfere with phosphorylation of the receptor, thereby inhibiting down-regulation of the receptor. The mechanism explains how enhancers potentiate aminergic activity and increase duration of activity and makes testable predictions about additional compounds that should act as aminergic enhancers.

  16. Regulation of opioid receptor signalling: Implications for the development of analgesic tolerance

    Directory of Open Access Journals (Sweden)

    Nagi Karim

    2011-06-01

    Full Text Available Abstract Opiate drugs are the most effective analgesics available but their clinical use is restricted by severe side effects. Some of these undesired actions appear after repeated administration and are related to adaptive changes directed at counteracting the consequences of sustained opioid receptor activation. Here we will discuss adaptations that contribute to the development of tolerance. The focus of the first part of the review is set on molecular mechanisms involved in the regulation of opioid receptor signalling in heterologous expression systems and neurons. In the second part we assess how adaptations that take place in vivo may contribute to analgesic tolerance developed during repeated opioid administration.

  17. The use of bifunctional NOP/mu and NOP receptor selective compounds for the treatment of pain, drug abuse, and psychiatric disorders.

    Science.gov (United States)

    Toll, Lawrence

    2013-01-01

    The NOP receptor, the fourth receptor in the opioid receptor family, is found throughout the brain and is involved in a variety of CNS systems and pathways. The endogenous ligand for NOP receptors, nociceptin/orphanin FQ (now called N/OFQ), was originally thought to increase a painful stimulus since intracerebroventricular (i.c.v.) administration of this heptadecapeptide led to a decrease in tail-flick and hot-plate latency in mice. Further studies suggested that N/OFQ blocks opiate analgesia when administered i.c.v. but potentiates opiate analgesia and has antinociceptive activity when administered intrathecally. I.c.v. administration of N/OFQ has other beneficial actions including inhibition of reward induced by several different abused drugs, as well as anti-anxiety activity. Recent work has demonstrated that individual small molecules that activate both NOP and mu receptors possess mu-mediated antinociceptive activity with reduced reward, as determined by conditioned place preference tests. Furthermore, selective NOP receptor agonists appear to be active in certain chronic pain models and reduce both drug craving and anxiety. NOP receptor antagonists may also have therapeutic benefits since both peptide and small molecule antagonists have anti-depressant activity in two different animal models. Therefore, both selective NOP receptor compounds and non-selective compounds, with both NOP receptor and mu opioid receptor activity, appear to have potential for clinical use for several neurological and psychiatric disorders including acute and chronic pain, drug abuse, anxiety and depression.

  18. Investigating the relationship between sexual and chemical addictions by comparing executive function in subjects with pedophilia or opiate addiction and healthy controls.

    Science.gov (United States)

    Cohen, Lisa J; Nesci, Cristina; Steinfeld, Matthew; Haeri, Sophia; Galynker, Igor

    2010-11-01

    Disorders of driven sexual behavior have been conceptualized as sexual addictions. In the following study, we compared 51 subjects with pedophilia, 53 subjects with opiate addiction, and 84 healthy control subjects on neuropsychological tests that tap executive functions. The test battery included the Wisconsin Card Sorting Test (WCST), Stroop Color-Word Test, the Matching Familiar Figures Test (MFFT), Porteus Mazes, Controlled Word Association (COWA), and Trailmaking Test. The groups differed on tests of cognitive flexibility and set switching (WCST), sustained attention (Stroop), and impulsivity (MFFT and Porteus Mazes). There were no differences on verbal fluency (COWA). The subjects with pedophilia differed significantly from those with opiate addiction on several tests, with longer latency to response on MFFT and fewer completed mazes but also fewer errors on Porteus Mazes. Thus, while both subjects with pedophilia and those with opiate addiction show executive dysfunction, the nature of that dysfunction may differ between the two groups; specifically, opiate addicted subjects may be more prone to cognitive impulsivity.

  19. The Impact of Take-Home Naloxone Distribution and Training on Opiate Overdose Knowledge and Response: An Evaluation of the THN Project in Wales

    Science.gov (United States)

    Bennett, Trevor; Holloway, Katy

    2012-01-01

    Aims: To determine the impact of naloxone training on knowledge of opiate overdose and confidence and willingness to take appropriate action and to examine the use of naloxone and other harm-reduction actions at the time of overdose events. Methods: The evaluation was based on a repeated-measure design, whereby clients were tested before and after…

  20. Reliability of self-reported use of amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates among acutely hospitalized elderly medical patients

    DEFF Research Database (Denmark)

    Glintborg, B.; Olsen, L.; Poulsen, H.

    2008-01-01

    Undisclosed use of illicit drugs and prescription controlled substances is frequent in some settings. The aim of the present study was to estimate the reliability of self-reported use of amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates among acutely...

  1. The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS prisons project: a randomised controlled trial comparing dihydrocodeine and buprenorphine for opiate detoxification

    Directory of Open Access Journals (Sweden)

    Li Ryan

    2009-02-01

    Full Text Available Abstract Background Many opiate users entering British prisons require prescribed medication to help them achieve abstinence. This commonly takes the form of a detoxification regime. Previously, a range of detoxification agents have been prescribed without a clear evidence base to recommend a drug of choice. There are few trials and very few in the prison setting. This study compares dihydrocodeine with buprenorphine. Methods Open label, pragmatic, randomised controlled trial in a large remand prison in the North of England. Ninety adult male prisoners requesting an opiate detoxification were randomised to receive either daily sublingual buprenorphine or daily oral dihydrocodeine, given in the context of routine care. All participants gave written, informed consent. Reducing regimens were within a standard regimen of not more than 20 days and were at the discretion of the prescribing doctor. Primary outcome was abstinence from illicit opiates as indicated by a urine test at five days post detoxification. Secondary outcomes were collected during the detoxification period and then at one, three and six months post detoxification. Analysis was undertaken using relative risk tests for categorical data and unpaired t-tests for continuous data. Results 64% of those approached took part in the study. 63 men (70% gave a urine sample at five days post detoxification. At the completion of detoxification, by intention to treat analysis, a higher proportion of people allocated to buprenorphine provided a urine sample negative for opiates (abstinent compared with those who received dihydrocodeine (57% vs 35%, RR 1.61 CI 1.02–2.56. At the 1, 3 and 6 month follow-up points, there were no significant differences for urine samples negative for opiates between the two groups. Follow up rates were low for those participants who had subsequently been released into the community. Conclusion These findings would suggest that dihydrocodeine should not be routinely

  2. Comparison of childhood sexual histories in subjects with pedophilia or opiate addiction and healthy controls: is childhood sexual abuse a risk factor for addictions?

    Science.gov (United States)

    Cohen, Lisa J; Forman, Howard; Steinfeld, Matthew; Fradkin, Yuli; Frenda, Steven; Galynker, Igor

    2010-11-01

    Given the recent interest in the concept of sexual addictions, it is instructive to study subjects with pedophilia alongside chemically addicted individuals and non-addicted controls in order to help identify which factors may determine the objects of people's respective addictions, as well as any factors that may predispose people to developing an addictive disorder. In this study, we considered whether childhood sexual abuse (CSA) is a specific risk factor for pedophilia as opposed to other types of addictive disorders by comparing the childhood sexual histories of 48 pedophilic sex offenders, 25 subjects with opiate addiction in remission, and 61 healthy controls. CSA was assessed with The Sexual History Questionnaire and the Child Trauma Questionnaire (CTQ). Compared with both opiate addicted subjects and healthy controls, subjects with pedophilia were more likely to report experiencing adult sexual advances when they were children and a first sexual contact by age 13 with a partner at least 5 years older. Although both subjects with pedophilia and those with opiate addiction first had sex at a younger age than healthy controls, opiate addicted subjects, compared with healthy controls, reported neither increased reception of sexual advances as children nor increased rates of first sexual contact before age 13 with a partner at least 5 years older. Further, subjects with pedophilia but not those with opiate addiction scored significantly higher than healthy controls on the CTQ. Sexual abuse in childhood may be a specific risk factor for sexual addictions such as pedophilia but may not be a specific risk factor for chemical addictions.

  3. Opioid receptor imaging and displacement studies with [6-O-[{sup 11}C]methyl]buprenorphine in baboon brain

    Energy Technology Data Exchange (ETDEWEB)

    Galynker, Igor; Schlyer, David J.; Dewey, Stephen L.; Fowler, Joanna S.; Logan, Jean; Gatley, S. John; MacGregor, Robert R.; Ferrieri, Richard A.; Holland, M. J.; Brodie, Jonathan; Simon, Eric; Wolf, Alfred P

    1996-04-01

    Buprenorphine (BPN) is a mixed opiate agonist-antagonist used as an analgesic and in the treatment of opiate addiction. We have used [6-O-[{sup 11}C]methyl]buprenorphine ([{sup 11}C]BPN) to measure the regional distribution in baboon brain, the test-retest stability of repeated studies in the same animal, the displacement of the labeled drug by naloxone in vivo, and the tissue distribution in mice. The regional distribution of radioactivity in baboon brain determined with PET was striatum > thalamus > cingulate gyrus > frontal cortex > parietal cortex > occipital cortex > cerebellum. This distribution corresponded to opiate receptor density and to previously published data (37). The tracer uptake in adult female baboons showed no significant variation in serial scans in the same baboon with no intervention in the same scanning session. HPLC analysis of baboon plasma showed the presence of labeled metabolites with 92% {+-} 2.2% and 43% {+-} 14.4% of the intact tracer remaining at 5 and 30 min, respectively. Naloxone, an opiate receptor antagonist, administered 30-40 min after tracer injection at a dose of 1.0 mg/kg i.v., reduced [{sup 11}C]BPN binding in thalamus, striatum, cingulate gyrus, and frontal cortex to values 0.25 to 0.60 of that with no intervention. There were minimal (< 15%) effects on cerebellum. Naloxone treatment significantly reduced the slope of the Patlak plot in receptor-containing regions. These results demonstrate that [{sup 11}C]BPN can be displaced by naloxone in vivo, and they affirm the feasibility of using this tracer and displacement methodology for short-term kinetics studies with PET. Mouse tissue distribution data were used to estimate the radiation dosimetry to humans. The critical organ was the small intestine, with a radiation dose estimate to humans of 117 nrad/mCi.

  4. Molecular modeling of interactions of the non-peptide antagonist YM087 with the human vasopressin V1a, V2 receptors and with oxytocin receptors.

    Science.gov (United States)

    Giełdoń, Artur; Kaźmierkiewicz, Rajmund; Ślusarz, Rafał; Ciarkowski, Jerzy

    2001-12-01

    The nonapeptide hormones arginine vasopressin (CYFQNCPRG-NH2, AVP) and oxytocin (CYIQNCPLG-NH2, OT), control many essential functions in mammals. Their main activities include the urine concentration (via stimulation of AVP V2 receptors, V2R, in the kidneys), blood pressure regulation (via stimulation of vascular V1a AVP receptors, V1aR), ACTH control (via stimulation of V1b receptors, V1bR, in the pituitary) and labor and lactation control (via stimulation of OT receptors, OTR, in the uterus and nipples, respectively). All four receptor subtypes belong to the GTP-binding (G) protein-coupled receptor (GPCR) family. This work consists of docking of YM087, a potent non-peptide V1aR and V2R - but not OTR - antagonist, into the receptor models based on relatively new theoretical templates of rhodopsin (RD) and opiate receptors, proposed by Mosberg et al. (Univ. of Michigan, Ann Arbor, USA). It is simultaneously demonstrated that this RD template satisfactorily compares with the first historical GPCR structure of bovine rhodopsin (Palczewski et al., 2000) and that homology-modeling of V2R, V1aR and OTR using opiate receptors as templates is rational, based on relatively high (20-60%) sequence homology among the set of 4 neurophyseal and 4 opiate receptors. YM087 was computer-docked to V1aR, V2R and OTR using the AutoDock (Olson et al., Scripps Research Institute, La Jolla, USA) and subsequently relaxed using restrained simulated annealing and molecular dynamics, as implemented in AMBER program (Kollman et al., University of California, San Francisco, USA). From about 80 diverse configurations, sampled for each of the three ligand/receptor systems, 3 best energy-relaxed complexes were selected for mutual comparisons. Similar docking modes were found for the YM087/V1aR and YM087/V2R complexes, diverse from those of the YM087/OTR complexes, in agreement with the molecular affinity data.

  5. Rapid simultaneous determination of ephedrines, amphetamines, cocaine, cocaine metabolites, and opiates in human urine by GC-MS.

    Science.gov (United States)

    Saito, Takeshi; Mase, Hiroyasu; Takeichi, Sanae; Inokuchi, Sadaki

    2007-01-04

    This paper presents a simple and sensitive chromatographic procedure for the simultaneous determination and quantification of ephedrines, amphetamines, cocaine, cocaine metabolites, and opiates in human urine by gas chromatography-mass spectrometry. This method involves enzyme hydrolysis in the presence of a deuterated internal standard, liquid-liquid extraction, and derivatization with pentafluoropropionic anhydride and pentafluoropropanol. The recovery of each compound averaged at 65.8% or more. The limits of detection determined for each compound by using a 2-mL sample volume ranged from 5 to 50 ng/mL. The calibration curves were linear to 100 ng/mL for all compounds when determined using methamphetamine-d4 and MDMA-d5 as internal standards. This method was successfully applied for the analysis of urine samples suspected to contain intoxicants such as methamphetamine and heroin.

  6. Performance characteristics of DRI, CEDIA, and REMEDi systems for preliminary tests of amphetamines and opiates in human urine.

    Science.gov (United States)

    Huang, Min-Kun; Dai, Yu-Shan; Lee, Choung-Huei; Liu, Chiareiy; Tsay, Wen-Ing; Li, Jih-Heng

    2006-01-01

    Arrestee urine specimens (930) were tested with DRI, CEDIA, and REMEDi; those that tested positive for amphetamines and opiates (616 and 414, respectively) were then confirmed by gas chromatography-mass spectrometry. The performance characteristics of these three preliminary systems were evaluated using the following commonly used parameters: true positive, true negative, false positive, and false negative. The sensitivity, specificity, and efficiency of these methods were also calculated. Data derived from this study indicated DRI and CEDIA adapted by this study generated acceptable preliminary test results for amphetamine/methamphetamine and morphine/codeine, but not for MDA/MDMA and REMEDi has lower sensitivity than DRI and CEDIA, but with better specificity and efficiency, supporting its use under emergency room settings where drug concentrations in overdose cases are expectedly at high levels.

  7. Poverty and fatal accidental drug overdoses of cocaine and opiates in New York City: an ecological study.

    Science.gov (United States)

    Marzuk, P M; Tardiff, K; Leon, A C; Hirsch, C S; Stajic, M; Portera, L; Hartwell, N

    1997-05-01

    This ecological study examines the association of the poverty status of urban communities in New York City with their mortality rates of accidental drug overdoses. Mean annual age-adjusted rates of drug overdoses involving cocaine, opiates, or both (n = 1,684) were calculated for each of 59 residential community districts in New York City for 1990-1992. A linear regression analysis was performed to test the association of the mortality rate with the poverty status of the district as measured by the proportion of the district living below the 1989 U.S. poverty line. Poverty status accounted for 69% of the variance in the drug overdose mortality rates of communities (p poverty status of communities in New York City.

  8. PET in neuroscience. Dopaminergic, CABA/benzodiazepine, and opiate system; PET in den Neurowisssenschaften: dopaminerges, GABA/Benzodiazepin- und Opiatsystem

    Energy Technology Data Exchange (ETDEWEB)

    Bartenstein, P. [Mainz Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin

    2004-02-01

    This article gives an overview on radiotracer imaging with positron emission tomography (PET) in measuring various aspects of neurotransmission. The review focusses on the dopaminergic system, the GABA/benzodiazepine system, and the opiate system. Besides dealing with the current clinical applications for brain PET studies with specific radiopharmaceuticals this article outlines an idea on potential future developments for the use of these methods in basic neuroscience. (orig.) [German] Diese Arbeit praesentiert eine Uebersicht zur aktuellen Forschung und klinischen Anwendung von PET-Untersuchungen mit Radiopharmaka, die verschiedene Komponenten der Neurotransmission erfassen. Ausserdem werden Perspektiven und Trend der Methodik gezeigt. Im Mittelpunkt stehen das dopaminerge System, das GABA/Benzodiazepinsystem, und das Opiatsystem. Ausfuehrlich dargestellt werden aktuelle klinische und kliniknahe Moeglichkeiten sowie methodische Aspekte der grundlagenorientierten Forschung, die fuer eine zukunftsorientierte Anwendung von PET-Studien mit Rezeptorliganden u.a. Radiopharmaka zur Bildgebung komplexer biochemischer Prozesse von Bedeutung sind. (orig.)

  9. Glucocorticoids regulation of FosB/ΔFosB expression induced by chronic opiate exposure in the brain stress system.

    Directory of Open Access Journals (Sweden)

    Daniel García-Pérez

    Full Text Available Chronic use of drugs of abuse profoundly alters stress-responsive system. Repeated exposure to morphine leads to accumulation of the transcription factor ΔFosB, particularly in brain areas associated with reward and stress. The persistent effects of ΔFosB on target genes may play an important role in the plasticity induced by drugs of abuse. Recent evidence suggests that stress-related hormones (e.g., glucocorticoids, GC may induce adaptations in the brain stress system that is likely to involve alteration in gene expression and transcription factors. This study examined the role of GC in regulation of FosB/ΔFosB in both hypothalamic and extrahypothalamic brain stress systems during morphine dependence. For that, expression of FosB/ΔFosB was measured in control (sham-operated and adrenalectomized (ADX rats that were made opiate dependent after ten days of morphine treatment. In sham-operated rats, FosB/ΔFosB was induced after chronic morphine administration in all the brain stress areas investigated: nucleus accumbens(shell (NAc, bed nucleus of the stria terminalis (BNST, central amygdala (CeA, hypothalamic paraventricular nucleus (PVN and nucleus of the solitary tract noradrenergic cell group (NTS-A(2. Adrenalectomy attenuated the increased production of FosB/ΔFosB observed after chronic morphine exposure in NAc, CeA, and NTS. Furthermore, ADX decreased expression of FosB/ΔFosB within CRH-positive neurons of the BNST, PVN and CeA. Similar results were obtained in NTS-A(2 TH-positive neurons and NAc pro-dynorphin-positive neurons. These data suggest that neuroadaptation (estimated as accumulation of FosB/ΔFosB to opiates in brain areas associated with stress is modulated by GC, supporting the evidence of a link between brain stress hormones and addiction.

  10. Simultaneous determination of opiates, methadone, buprenorphine and metabolites in human urine by superficially porous liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Lin, Huei-Ru; Chen, Chin-Lun; Huang, Chieh-Liang; Chen, Shao-Tsu; Lua, Ahai-Chuang

    2013-04-15

    For monitoring compliance of methadone or buprenorphine maintenance patient, a method for the simultaneous determination of methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, norbuprenorphine, opiates (morphine, codeine, 6-monoacetylmorphine) in urine by superficially porous liquid chromatography tandem mass spectrometry was developed and validated. After enzyme digestion and liquid-liquid extraction, reverse-phase separation was achieved in 5.2 min and quantification was performed by multiple reaction monitoring. Chromatographic separation was performed at 40 °C on a reversed phase Poroshell column with gradient elution. The mobile phase consisted of water and methanol, each containing 0.1% formic acid, at a flow rate of 0.32 mL/min. Intra-day and inter-day precision were less than 12.1% and accuracy was between -9.8% and 13.7%. Extraction efficiencies were more than 68%. Although ion suppression was detected, deuterated internal standards compensated for these effects. Carryover was minimal, less than 0.20%. All analytes were stable at room temperature for 16 h, 4 °C for 72 h, and after three freeze-thaw cycles. The assay also fulfilled compound identification criteria in accordance with the European Commission Decision 2002/657/EC. We analyzed 62 urine samples from patients received maintenance therapy and found that 54.8% of the patient samples tested were detected for morphine, codeine, or 6-monoacetylmorphine. This method provides a reliable and simultaneous quantification of opiates, maintenance drugs, and their metabolites in urine samples. It facilitates the routine monitoring in individuals prescribed the drug to ensure compliance and help therapeutic process.

  11. Psychosocial and treatment correlates of opiate free success in a clinical review of a naltrexone implant program

    Directory of Open Access Journals (Sweden)

    Reece AS

    2007-11-01

    Full Text Available Abstract Background There is on-going controversy in relation to the efficacy of naltrexone used for the treatment of heroin addiction, and the important covariates of that success. We were also interested to review our experience with two depot forms of implantable naltrexone. Methods A retrospective review of patients' charts was undertaken, patients were recalled by telephone and by letter, and urine drug screen samples were collected. Opiate free success (OFS was the parameter of interest. Three groups were defined. The first two were treated in the previous 12 months and comprised "implant" and "tablet" patients. A third group was "historical" comprising those treated orally in the preceding 12 months. Results There were 102, 113 and 161 patients in each group respectively. Groups were matched for age, sex, and dose of heroin used, but not financial status or social support. The overall follow-up rate was 82%. The Kaplan Meier 12 month OFS were 82%, 58% and 52% respectively. 12 post-treatment variables were independently associated with treatment retention. In a Cox proportional hazard multivariate model social support, the number of detoxification episodes, post-treatment employment, the use of multiple implant episodes and spiritual belief were significantly related to OFS. Conclusion Consistent with the voluminous international literature clinically useful retention rates can be achieved with naltrexone, which may be improved by implants and particularly serial implants, repeat detoxification, meticulous clinical follow-up, and social support. As depot formulations of naltrexone become increasingly available such results can guide their clinical deployment, improve treatment outcomes, and enlarge the policy options for an exciting non-addictive pharmacotherapy for opiate addiction.

  12. Psychometric evaluation of the 10-item Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in patients undergoing opioid detoxification.

    Science.gov (United States)

    Vernon, Margaret K; Reinders, Stefan; Mannix, Sally; Gullo, Kristen; Gorodetzky, Charles W; Clinch, Thomas

    2016-09-01

    The Short Opiate Withdrawal Scale (SOWS)-Gossop is a 10-item questionnaire developed to evaluate opioid withdrawal symptom severity. The scale was derived from the original 32-item Opiate Withdrawal Scale in order to reduce redundancy while providing an equally sensitive measure of opioid withdrawal symptom severity appropriate for research and clinical practice. The objective of this study was to examine the psychometric properties and provide score interpretation guidelines for the SOWS-Gossop 10-item version. Blinded, pooled data from two trials assessing the efficacy of lofexidine hydrochloride in reducing withdrawal symptoms in patients undergoing opioid detoxification were used to evaluate the quantitative psychometric properties and score interpretation of the SOWS-Gossop. Five hundred fifty-five (N=555) observations were available at baseline with numbers decreasing to n=213 at day 7. Mean (standard deviation) SOWS-Gossop scores were 10.4 (6.86) at baseline, 8.7 (6.49) on day 1, 10.5 (7.21) on day 2, and 3.1 (3.95) on day 7. Confirmatory factor analysis indicated that the SOWS-Gossop items loaded on a single factor consistent with a single total score. Intra-class correlations (95% confidence interval) were 0.78 (0.70-0.85) between baseline and day 1, 0.84 (0.79-0.89) between days 4 and 5, and 0.88 (0.83-0.91) between days 6 and 7, demonstrating good test-retest reliability. Mean SOWS-Gossop scores varied significantly (pSOWS-Gossop Total Score. The findings of this study indicate that the SOWS-Gossop includes concepts that are relevant to patients' experiences with opioid withdrawal and has excellent psychometric properties. The SOWS-Gossop is an appropriate, precise, and sensitive measure to evaluate the symptoms of acute opioid withdrawal in research or clinical settings. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Endogenous Opiates in the Nucleus Tractus Solitarius Mediate Electroacupuncture-Induced Sleep Activities in Rats

    Directory of Open Access Journals (Sweden)

    Chiung-Hsiang Cheng

    2011-01-01

    Full Text Available Electroacupuncture (EA possesses various therapeutic effects, including alleviation of pain, reduction of inflammation and improvement of sleep disturbance. The mechanisms of EA on sleep improvement, however, remain to be determined. It has been stated in ancient Chinese literature that the Anmian (EX17 acupoint is one of the trigger points that alleviates insomnia. We previously demonstrated that EA stimulation of Anmian acupoints in rats during the dark period enhances non-rapid eye movement (NREM sleep, which involves the induction of cholinergic activity in the nucleus tractus solitarius (NTS. In addition to cholinergic activation of the NTS, activation of the endogenous opioidergic system may also be a mechanism by which acupuncture affects sleep. Therefore, this study was designed to investigate the involvement of the NTS opioidergic system in EA-induced alterations in sleep. Our present results indicate that EA of Anmian acupoints increased NREM sleep, but not rapid eye movement sleep, during the dark period in rats. This enhancement in NREM sleep was dose-dependently blocked by microinjection of opioid receptor antagonist, naloxone, and the μ-opioid receptor antagonist, naloxonazine, into the NTS; administrations of δ-receptor antagonist, natrindole, and the κ-receptor antagonist, nor-binaltrophimine, however, did not affect EA-induced alterations in sleep. Furthermore, β-endorphin was significantly increased in both the brainstem and hippocampus after the EA stimuli, an effect blocked by administration of the muscarinic antagonist scopolamine into the NTS. Our findings suggest that mechanisms of EA-induced NREM sleep enhancement may be mediated, in part, by cholinergic activation, stimulation of the opiodergic neurons to increase the concentrations of β-endorphin and the involvement of the μ-opioid receptors.

  14. Galanin-induced decreases in nucleus accumbens/striatum excitatory postsynaptic potentials and morphine conditioned place preference require both galanin receptor 1 and galanin receptor 2.

    Science.gov (United States)

    Einstein, Emily B; Asaka, Yukiko; Yeckel, Mark F; Higley, Michael J; Picciotto, Marina R

    2013-05-01

    The neuropeptide galanin has been shown to alter the rewarding properties of morphine. To identify potential cellular mechanisms that might be involved in the ability of galanin to modulate opiate reward, we measured excitatory postsynaptic potentials (EPSPs), using both field and whole-cell recordings from striatal brain slices extracted from wild-type mice and mice lacking specific galanin receptor (GalR) subtypes. We found that galanin decreased the amplitude of EPSPs in both the dorsal striatum and nucleus accumbens. We then performed recordings in slices from knockout mice lacking either the GalR1 or GalR2 gene, and found that the ability of galanin to decrease EPSP amplitude was absent from both mouse lines, suggesting that both receptor subtypes are required for this effect. In order to determine whether behavioral responses to opiates were dependent on the same receptor subtypes, we tested GalR1 and GalR2 knockout mice for morphine conditioned place preference (CPP). Morphine CPP was significantly attenuated in both GalR1 and GalR2 knockout mice. These data suggest that mesolimbic excitatory signaling is significantly modulated by galanin in a GalR1-dependent and GalR2-dependent manner, and that morphine CPP is dependent on the same receptor subtypes.

  15. Morphine induces μ opioid receptor endocytosis in guinea pig enteric neurons following prolonged receptor activation

    Science.gov (United States)

    Patierno, Simona; Anselmi, Laura; Jaramillo, Ingrid; Scott, David; Garcia, Rachel; Sternini, Catia

    2010-01-01

    Background & Aims The μ opioid receptor (μOR) undergoes rapid endocytosis following acute stimulation with opioids and most opiates, but not with morphine. We investigated whether prolonged activation of μOR affects morphine’s ability to induce receptor endocytosis in enteric neurons. Methods We compared the effects of morphine, a poor μOR-internalizing opiate, and [D-Ala2, MePhe4,Gly-ol5] enkephalin (DAMGO), a potent μOR-internalizing agonist, on μOR trafficking in enteric neurons and on the expression of dynamin and β-arrestin immunoreactivity in the ileum of guinea pigs rendered tolerant by chronic administration of morphine. Results Morphine (100 µM) strongly induced endocytosis of μOR in tolerant but not naïve neurons (55.7%±9.3% vs. 24.2%±7.3%, P<0.001) whereas DAMGO (10 µM) strongly induced internalization of μOR in neurons from tolerant and naïve animals (63.6%±8.4% and 66.5%±3.6%). Morphine- or DAMGO-induced μOR endocytosis resulted from direct interactions between the ligand and the μOR, because endocytosis was not affected by tetrodotoxin, a blocker of endogenous neurotransmitter release. Ligand-induced μOR internalization was inhibited by pretreatment with the dynamin inhibitor, dynasore. Chronic morphine administration resulted in a significant increase in dynamin and translocation of dynamin immunoreactivity from the intracellular pool to the plasma membrane, but did not affect β arrestin immunoreactivity. Conclusion Chronic activation of μORs increases the ability of morphine to induce μOR endocytosis in enteric neurons, which depends on the level and cellular localization of dynamin, a regulatory protein that has an important role in receptor-mediated signal transduction in cells. PMID:21070774

  16. The imidazoline receptors and ligands in pain modulation

    Directory of Open Access Journals (Sweden)

    Nurcan Bektas

    2015-01-01

    Full Text Available Pain is an unpleasant experience and effects daily routine negatively. Although there are various drugs, many of them are not entirely successful in relieving pain, since pain modulation is a complex process involving numerous mediators and receptors. Therefore, it is a rational approach to identify the factors involved in the complex process and develop new agents that act on these pain producing mechanisms. In this respect, the involvement of the imidazoline receptors in pain modulation has drawn attention in recent years. In this review, it is aimed to focus on the imidazoline receptors and their ligands which contribute to the pain modulation. It is demonstrated that imidazoline-2 (I2 receptors are steady new drug targets for analgesics. Even if the mechanism of I2receptor is not well known in the modulation of pain, it is known that it plays a role in tonic and chronic pain but not in acute phasic pain. Moreover, the I2receptor ligands increase the analgesic effects of opioids in both acute and chronic pain and prevent the development of opioid tolerance. So, they are valuable for the chronic pain treatment and also therapeutic coadjuvants in the management of chronic pain with opiate drugs due to the attenuation of opioid tolerance and addiction. Thus, the use of the ligands which bind to the imidazoline receptors is an effective strategy for relieving pain. This educational forum exhibits the role of imidazoline receptors and ligands in pain process by utilizing experimental studies.

  17. Epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, R.S.; Frost, J.J. (Johns Hopkins Univ., Baltimore, MD (USA))

    1991-04-01

    As surgical treatments for adult and pediatric forms of epilepsy have become more refined, methods for noninvasive localization of epileptogenic foci have become increasingly important. Detection of focal brain metabolic or flow abnormalities is now well recognized as an essential step in the presurgical evaluation of many patients with epilepsy. Positron emission tomography (PET) scanning is most beneficial when used in the context of the total clinical evaluation of patients, including scalp EEG, invasive EEG, neuropsychologic testing, etc. Metabolic PET studies also give insight into pathophysiologic mechanisms of epilepsy. The dynamic nature of the interictal hypometabolism observed with 18(F)FDG in some patients suggests that excitatory or inhibitory neurotransmitters and their receptors may be involved. An exciting current application of PET scanning is the use of tracers for neurotransmitter receptors in the study of epilepsy patients. Mu and non-mu opiate receptors have been extensively studied and are beginning to give new insights into this disorder. Increased labeling of mu receptors in temporal neocortex using 11C-carfentanil has been demonstrated and, in some patients, supplements the clinical localization information from 18(F)FDG studies. Increased mu opiate receptor number or affinity is thought to play a role in anticonvulsant mechanisms. Specificity of increased mu receptors is supported by the absence of significant changes in non-mu opiate receptors. Other brain receptors are also of interest for future studies, particularly those for excitatory neurotransmitters. Combined studies of flow, metabolism, and neuroreceptors may elucidate the factors responsible for initiation and termination of seizures, thus improving patient treatment.95 references.

  18. A comparison of locomotor responses to some psychotropic drugs and cerebral receptors in the Acomys cahirinus and the laboratory mouse.

    Science.gov (United States)

    Marona-Lewicka, D; Michaluk, J; Antkiewicz-Michaluk, L; Vetulani, J

    1987-01-01

    Comparative studies of the laboratory mouse and Acomys cahirinus have shown differences in their motor activity patterns and motor responses to morphine, apomorphine and clonidine. The two species also differed in respect of the density of cerebral alpha 2-adrenergic receptors, but no significant differences between other types of receptors (alpha 1-adrenergic, beta-adrenergic, opiate mu and delta, and spiroperidol binding sites) were found. It is suggested that the high excitability of the Acomys may be related to a deficit in the inhibitory noradrenergic transmission in the central nervous system.

  19. Specific binding of a ligand of sigma-opioid receptors - N-allylnormetazocine (SKF 10047) - with liver membranes

    Energy Technology Data Exchange (ETDEWEB)

    Samovilova, N.N.; Yarygin, K.N.; Vinogradov, V.A.

    1986-08-01

    A ligand of the sigma-opioid receptors - N-allylnormetazocine (SKF 10047) -binds specifically and reversible with rat liver membranes. In relation to a number of properties, the sites binding SKF 10047 in the liver are similar to the sigma-opioid receptors of the central nervous system. They do not interact with classical opiates (morphine, naloxone) and with opioid peptides, but bind well benzomorphans (bremazocine, SKF 10047) and a number of compounds of different chemical structures with a pronounced psychtropic action (haloperidol, imipramine, phencyclidine, etc.).

  20. Anti-opioid effects of neuropeptide FF receptors in the ventral tegmental area.

    Science.gov (United States)

    Kersanté, Flavie; Wang, Jin-Ya; Chen, Jin-Chung; Mollereau, Catherine; Zajac, Jean-Marie

    2011-01-25

    The present study investigates the modulatory effects of neuropeptide FF (NPFF) receptors on the mesolimbic dopaminergic pathway controlled by opioid receptors. A stable NPFF(2) receptor agonist, dNPA, was injected into the ventral tegmental area (VTA) and the release of dopamine and serotonin within the nucleus accumbens (NAc), induced by intraperitoneal injection of morphine, was monitored using the brain microdialysis, in non-constrained rat. dNPA decreased systemic morphine-induced elevation of dopamine and serotonin metabolites within the NAc. Furthermore, co-injected with morphine into the VTA, NPFF inhibited morphine-induced stereotypy 60-120min after the injection. This neurochemical and behavioural anti-opioid effect mediated by NPFF(2) receptors at the level of VTA suggests the involvement of NPFF in the rewarding effects of opiates on the mesolimbic dopamine system.

  1. 阿片类药物成瘾者执行功能的研究进展%Review on Executive Functions of Opiate Addicts

    Institute of Scientific and Technical Information of China (English)

    朱千

    2015-01-01

    Executive functions play an important role in the course of forming,maintenance,treatment and relapse of opiate addic-tion. Long-term chronic opioids abuse can cause the executive functions of addicts generally damaged,then affect the treatment and re-lapse of opiate addiction. The present article reviewed the research results related to executive functions in the field of neuropsychology, event-related potentials and imageology,attempting to provide the scientific basis from cognitive neuroscience for the work on the treat-ment of opiate addiction in China.%执行功能在阿片成瘾的形成、维持、戒治与复发中都具有重要作用。长期慢性的阿片类药物滥用会导致成瘾者的执行功能普遍受到损伤,继而影响药物成瘾的戒治与复发。本文梳理了近年来阿片类药物在神经心理学、事件相关电位以及影像学等领域的执行功能相关研究结果,以期为我国的阿片类药物成瘾的戒治工作提供来自认知神经科学的科学依据。

  2. The Comparison of Early Maladaptive Schema’s Domains Between Successful And Non-Successful Opiate Addicts and Non-Clinical Persons

    Directory of Open Access Journals (Sweden)

    Bahram Sahand

    2009-10-01

    Full Text Available Introduction: The current research was done in order to compare the early maladaptive schema’s domains between successful and non-successful opiate addicts and non-clinical persons in Tehran. Method: The research design was causal effect method. In this purpose 90 men (include successful and non-successful opiate addicts, and non-clinical persons (30 for each group, were selected by the available sampling method. Young Schema Questionnaire (YSQ-RE2R, General Health Questionnaire (GHQ, and Personal Characteristic Questionnaire were administered among selected sample. The results were analyzed by ANOVA, chi square, MANOVA, and tukey test. Results: The findings of this research indicated that there was a significant difference on “Early Maladaptive Schema’s domains” between these three groups. Conclusion: The results have important clinical interpretations. It is assumed that medical interference with the aim of modifying and correcting the “Early Maladaptive Schema’s domains” can be effective on the level of success for opiate addicts to give up their addiction.

  3. 阿片类成瘾者脱毒后感受的质性研究%Qualitative research on feelings after detoxification for opiates addicts

    Institute of Scientific and Technical Information of China (English)

    邢小珍; 杜荣荣; 张景明; 夏瑛

    2012-01-01

    Objective To study the feelings after detoxification by mcthadonc maintenance treatment for opiates addicts. Method Interview 14 opiates addicts after detoxification by phenomenology method from qualitative research. Result Conclude 3 themes by generic analysis, namely effective mcthadonc maintenance treatment, lonely and helpless, coping methods to avoiding re-addiction. Conclusion Opiates addicts arc facing many mental and social problems in community rehabilitation after detoxification. A community rehabilitation system should be established to help them return to the society.%目的 了解阿片类成瘾者经美沙酮维持治疗脱毒后的心理感受.方法 采用质性研究中的现象学方法,对14名脱毒者进行访谈.结果 采用类属分析法升华出3个主题:美沙酮替代治疗效果显著;孤独无助;避免复吸而采取各种应对方式.结论 阿片类成瘾者脱毒后,在社区康复中面临着诸多心理社会问题,需要建立社区康复机制以促进脱毒者的社会回归.

  4. 'Not just methadone Tracy': transformations in service-user identity following the introduction of hepatitis C treatment into Australian opiate substitution settings.

    Science.gov (United States)

    Rance, Jake; Treloar, Carla

    2014-03-01

    To explore identity transformation among service users attending opiate substitution therapy (OST) clinics following the introduction of hepatitis C (HCV) care and treatment. An interview-based substudy of the Australian ETHOS (Enhancing Treatment for Hepatitis C in Opiate Substitution Settings) project. Three OST clinics and one community health centre (operating a public OST) in New South Wales, Australia. Participants were interviewed at the recruitment sites. The sample consisted of 57 OST service users concurrently living with HCV, 16 staff, including specialist HCV clinicians, and three peer-support workers, employed on the ETHOS project. Semi-structured interviews. Service-user participants largely welcomed the introduction of HCV treatment as a practical, clinical intervention that also intimated a more comprehensive, holistic form of care. Negative stereotypes characteristic of OST settings-of limited, routinized clinical exchanges and minimal social-care interaction-were unsettled, opening up the possibility of new relations between staff and service users. The shift in the dynamic of the clinical encounter to address health in addition to dependence appeared to catalyse transformative possibilities not only for the therapeutic alliance but also for service-user understandings of self and identity. Trial introduction of HCV care and treatment in selected Australian opiate substitution therapy (OST) clinics may have facilitated alternative, 'non-addict' identities to emerge from a clinical setting where the stigmatizing figure of 'the drug user' has traditionally prevailed.

  5. The disposition of cocaine and opiate analytes in hair and fingernails of humans following cocaine and codeine administration.

    Science.gov (United States)

    Ropero-Miller, J D; Goldberger, B A; Cone, E J; Joseph, R E

    2000-10-01

    This study investigated the disposition patterns of cocaine and opiates into hair and fingernail specimens collected from 8 volunteers enrolled in a 10-week inpatient clinical study. All subjects were African-American males with a confirmed drug use history. Scalp hair and fingernail scrapings were collected weekly throughout the course of the study. Head hair was collected from the posterior vertex region, and fingernail scrapings were collected along the entire ventral surface of the nail plate. The specimens were introduced to successive decontamination washes including an isopropanol wash and three phosphate buffer washes. All decontamination washes were collected and analyzed. All specimens were enzymatically digested prior to being subjected to solid-phase extraction and derivatization. Analyses were performed using electron impact gas chromatography-mass spectrometry. Analytes investigated included eight cocaine analytes and five codeine analytes. The limit of quantitation for all analytes ranged from 0.1 to 0.5 ng/mg for both matrices. Cocaine was present at the highest concentrations of any analyte in both hair and nail. Benzoylecgonine and ecgonine methyl ester were the primary metabolites in both matrices and were typically less than 15% of cocaine concentrations. Codeine was the only opiate analyte identified in either hair or nail. Observed drug disposition profiles were different for hair and nails. A significant dose-response relationship was observed for hair specimens. The mean peak concentrations in hair after low dosing were half the concentration observed after high-dose administration. Generally, no clear relationship was evident between nail drug concentrations and dose. Decontamination washes removed less than 20% of the total drug present in hair, but removed most of the drug concentrations (60-100%) in nail. This investigation demonstrated that higher concentrations of drug were found in the subjects' hair than in their fingernails and that

  6. The Comparison of Attention Biases to Opiates in Substance Dependent and Treated Clients of Therapeutic Clinics and Narcotics Anonymous Memberships

    Directory of Open Access Journals (Sweden)

    Javad Enayat

    2012-11-01

    Full Text Available Aim: The purpose of this study was to compare the attention bias about tempting incentives related to opium materials in treated, addicted and normal people. Duration of consumption and treating were also considered. Method: In this causal-comparative study population was all addicted people who were referred to the rehabilitation offices, addiction treatment clinic, rebirthing centers and Narcotics Anonymous of East Azerbaijan. This study consisted of five groups of men, including addicted to opium materials which are divided into two groups namely: long consumption period and people with short consumption period, also, treated people including long term treated and short term treated, and a normal control group. Altogether, 103 selected people were studied. Sample groups were similar in terms of age, education, and sex. For measuring attention bias towards tempting stimuli related opiates, a words recognition test was used. This test included three subtests and one recognition test. The recognition scores for the three categories of words were measured. Results: The findings indicated that there was a difference in attention against opium material incentives between control group and the mild and severe consumers groups. Also there were significant differences between treated people with the short time distance and control group, and control group had less temptation and biases in comparison to the other groups. Finally, those who have mild consumption are threatened more in comparison with the control group. Conclusion: The findings have applied implications.

  7. Opiates, cocaine and alcohol combinations in accidental drug overdose deaths in New York City, 1990-98.

    Science.gov (United States)

    Coffin, Phillip O; Galea, Sandro; Ahern, Jennifer; Leon, Andrew C; Vlahov, David; Tardiff, Kenneth

    2003-06-01

    Accidental drug overdose contributes substantially to mortality among drug users. Multi-drug use has been documented as a key risk factor in overdose and overdose mortality in several studies. This study investigated the contribution of multiple drug combinations to overdose mortality trends. We collected data on all overdose deaths in New York City between 1990 and 1998 using records from the Office of the Chief Medical Examiner (OCME). We standardized yearly overdose death rates by age, sex and race to the 1990 census population for NYC to enable comparability between years relevant to this analysis. Opiates, cocaine and alcohol were the three drugs most commonly attributed as the cause of accidental overdose death by the OCME, accounting for 97.6% of all deaths; 57.8% of those deaths were attributed to two or more of these three drugs in combination. Accidental overdose deaths increased in 1990-93 and subsequently declined slightly in 1993-98. Changes in the rate of multi-drug combination deaths accounted for most of the change in overdose death rates, whereas single drug overdose death rates remained relatively stable. Trends in accidental overdose death rates within gender and racial/ethnic strata varied by drug combination suggesting different patterns of multi-drug use among different subpopulations. These data suggest that interventions to prevent accidental overdose mortality should address the use of drugs such as heroin, cocaine and alcohol in combination.

  8. Comparison of personality traits in pedophiles, abstinent opiate addicts, and healthy controls: considering pedophilia as an addictive behavior.

    Science.gov (United States)

    Cohen, Lisa J; Grebchenko, Yuli F; Steinfeld, Matthew; Frenda, Steven J; Galynker, Igor I

    2008-11-01

    To investigate the model of pedophilia as a disorder of addictive behavior, pedophiles and chemically addicted individuals were compared on personality traits potentially associated with impaired behavioral inhibition. Twenty-nine pedophiles, 25 opiate addicts (OA's), and 27 healthy controls were administered the Barratt Impulsivity Scale, Hare Psychopathy Checklist-Revised (PCL-R), and Structured Clinical Interview for DSM-V for Axis-II. OA's scored higher than either pedophiles or controls on the Barratt. Pedophiles and OA's scored higher than controls on all 3 Psychopathy Checklist-Revised scores but OA's scored marginally higher than pedophiles on factor 2 (behavioral) and total scores. On Structured Clinical Interview for DSM-V for Axis-II, pedophiles scored higher than controls on paranoid and schizoid scores whereas OA's did so on paranoid scores. Thus, both pedophiles and OA's may have elevated psychopathic traits and propensity toward cognitive distortions, as reflected in cluster A traits. Such similarities support the conceptualization of pedophilia as a behavioral addiction. Pedophiles may be less impulsive than OA's, however, and more prone toward cognitive distortions.

  9. Truncated G protein-coupled mu opioid receptor MOR-1 splice variants are targets for highly potent opioid analgesics lacking side effects.

    Science.gov (United States)

    Majumdar, Susruta; Grinnell, Steven; Le Rouzic, Valerie; Burgman, Maxim; Polikar, Lisa; Ansonoff, Michael; Pintar, John; Pan, Ying-Xian; Pasternak, Gavril W

    2011-12-06

    Pain remains a pervasive problem throughout medicine, transcending all specialty boundaries. Despite the extraordinary insights into pain and its mechanisms over the past few decades, few advances have been made with analgesics. Most pain remains treated by opiates, which have significant side effects that limit their utility. We now describe a potent opiate analgesic lacking the traditional side effects associated with classical opiates, including respiratory depression, significant constipation, physical dependence, and, perhaps most important, reinforcing behavior, demonstrating that it is possible to dissociate side effects from analgesia. Evidence indicates that this agent acts through a truncated, six-transmembrane variant of the G protein-coupled mu opioid receptor MOR-1. Although truncated splice variants have been reported for a number of G protein-coupled receptors, their functional relevance has been unclear. Our evidence now suggests that truncated variants can be physiologically important through heterodimerization, even when inactive alone, and can comprise new therapeutic targets, as illustrated by our unique opioid analgesics with a vastly improved pharmacological profile.

  10. A structural feature of the non-peptide ligand interactions with mice mu-opioid receptors.

    Science.gov (United States)

    Noori, Hamid R; Mucksch, Christian; Urbassek, Herbert M

    2014-01-01

    By binding to and activating the G-protein coupled μ-, κ- and δ-opioid receptors in the central nervous system, opiates are known to induce analgesic and sedative effects. In particular, non-peptide opioid ligands are often used in clinical applications to induce these therapeutically beneficial effects, due to their superior pharmacokinetics and bioavailability in comparison to endogenous neuropeptides. However, since opioid alkaloids are highly addictive substances, it is necessary to understand the exact mechanisms of their actions, specifically the ligand-binding properties of the target receptors, in order to safely apply opiates for therapeutic purposes. Using an in silico molecular docking approach (AutoDock Vina) combined with two-step cluster analysis, we have computationally obtained the docking scores and the ligand-binding pockets of twelve representative non-peptide nonendogenous agonists and antagonists at the crystallographically identified μ-opioid receptor. Our study predicts the existence of two main binding sites that are congruently present in all opioid receptor types. Interestingly, in terms of the agonist or antagonist properties of the substances on the receptors, the clustering analysis suggests a relationship with the position of the ligand-binding pockets, particularly its depth within the receptor structure. Furthermore, the binding affinity of the substances is directly correlated to the proximity of the binding pockets to the extracellular space. In conclusion, the results provide further insights into the structural features of the functional pharmacology of opioid receptors, suggesting the importance of the binding position of non-peptide agonists and antagonists- specifically the distance and the level of exposure to the extracellular space- to their dissociation kinetics and subsequent potency.

  11. Decision-making in stimulant and opiate addicts in protracted abstinence: evidence from computational modeling with pure users

    Science.gov (United States)

    Ahn, Woo-Young; Vasilev, Georgi; Lee, Sung-Ha; Busemeyer, Jerome R.; Kruschke, John K.; Bechara, Antoine; Vassileva, Jasmin

    2014-01-01

    Substance dependent individuals (SDI) often exhibit decision-making deficits; however, it remains unclear whether the nature of the underlying decision-making processes is the same in users of different classes of drugs and whether these deficits persist after discontinuation of drug use. We used computational modeling to address these questions in a unique sample of relatively “pure” amphetamine-dependent (N = 38) and heroin-dependent individuals (N = 43) who were currently in protracted abstinence, and in 48 healthy controls (HC). A Bayesian model comparison technique, a simulation method, and parameter recovery tests were used to compare three cognitive models: (1) Prospect Valence Learning with decay reinforcement learning rule (PVL-DecayRI), (2) PVL with delta learning rule (PVL-Delta), and (3) Value-Plus-Perseverance (VPP) model based on Win-Stay-Lose-Switch (WSLS) strategy. The model comparison results indicated that the VPP model, a hybrid model of reinforcement learning (RL) and a heuristic strategy of perseverance had the best post-hoc model fit, but the two PVL models showed better simulation and parameter recovery performance. Computational modeling results suggested that overall all three groups relied more on RL than on a WSLS strategy. Heroin users displayed reduced loss aversion relative to HC across all three models, which suggests that their decision-making deficits are longstanding (or pre-existing) and may be driven by reduced sensitivity to loss. In contrast, amphetamine users showed comparable cognitive functions to HC with the VPP model, whereas the second best-fitting model with relatively good simulation performance (PVL-DecayRI) revealed increased reward sensitivity relative to HC. These results suggest that some decision-making deficits persist in protracted abstinence and may be mediated by different mechanisms in opiate and stimulant users. PMID:25161631

  12. Decision-making in stimulant and opiate addicts in protracted abstinence: evidence from computational modeling with pure users

    Directory of Open Access Journals (Sweden)

    Woo-Young eAhn

    2014-08-01

    Full Text Available Substance dependent individuals (SDI often exhibit decision-making deficits; however, it remains unclear whether the nature of the underlying decision-making processes is the same in users of different classes of drugs and whether these deficits persist after discontinuation of drug use. We used computational modeling to address these questions in a unique sample of relatively pure amphetamine-dependent (N=38 and heroin-dependent individuals (N=43 who were currently in protracted abstinence, and in 48 healthy controls. A Bayesian model comparison technique, a simulation method, and parameter recovery tests were used to compare three cognitive models: (1 Prospect Valence Learning with decay reinforcement learning rule (PVL-DecayRI, (2 PVL with delta learning rule (PVL-Delta, and (3 Value-Plus-Perseverance (VPP models based on Win-Stay-Lose-Switch (WSLS strategy. The model comparison results indicated that the VPP model, a hybrid model of reinforcement learning (RL and a heuristic strategy of perseverance had the best post hoc model fit, but the two PVL models showed better simulation performance. Computational modeling results suggested that overall all three groups relied more on RL than on a WSLS strategy. Heroin users displayed reduced loss aversion relative to healthy controls across all three models, which suggests that their decision-making deficits are longstanding (or pre-existing and may be driven by reduced sensitivity to loss. In contrast, amphetamine users showed comparable cognitive functions to healthy controls with the VPP model, whereas the second best-fitting model with relatively good simulation performance (PVL-DecayRI revealed increased reward sensitivity relative to healthy controls. These results suggest that some decision-making deficits persist in protracted abstinence and may be mediated by different mechanisms in opiate and stimulant users.

  13. On-line liquid chromatography/tandem mass spectrometry simultaneous determination of opiates, cocainics and amphetamines in dried blood spots.

    Science.gov (United States)

    Saussereau, E; Lacroix, C; Gaulier, J M; Goulle, J P

    2012-02-15

    A novel approach has been developed for the illicit drugs quantitative determination using dried blood spots (DBS) on filter paper. The illicit drugs tested were opiates (morphine and its 3- and 6-glucuronide metabolites, codeine, 6-monoacetylmorphine), cocainics (ecgonine methylester, benzoylecgonine, cocaine, cocaethylene) and amphetamines (amphetamine, methamphetamine, MDA, MDMA, MDEA). The described method, requiring a small blood volume, is based on high performance liquid chromatography coupled to tandem mass spectrometry using on-line extraction. A Whatman card 903 was spotted with 30μL of whole blood and left overnight to dry at room temperature. A 3-mm diameter disk was removed using a manual punch, suspended in 150μL of water for 10min with ultrasonication, and then 100μL was injected in the on-line LC-MS/MS system. An Oasis HLB was used as an extraction column and a C18 Atlantis as an analytical column. The chromatographic cycle was performed with 20mM ammonium formate buffer (pH 2.8) (solvent A) and acetonitrile/solvent A (90:10, v/v) gradient in 16min. Detection was performed in positive electrospray ionization mode (ESI+) with a Quattro Micro (Waters). Recoveries of all analytes were up to 80%. DBS were stored in duplicate at 4°C and -20°C for up to 6 months. Illicit drugs seemed to be much more stabled at -20°C. Furthermore, it was tested whether analysis of DBS may be as reliable as that of whole blood investigating authentic samples; significant correlations were obtained. This DBS assay has potential as rapid, sensitive and inexpensive option for the illicit drugs determination in small blood volumes, which seems of great interest in suspected cases of driving under the influence of drugs.

  14. Unambiguous characterization of analytical markers in complex, seized opiate samples using an enhanced ion mobility trace detector-mass spectrometer.

    Science.gov (United States)

    Liuni, Peter; Romanov, Vladimir; Binette, Marie-Josée; Zaknoun, Hafid; Tam, Maggie; Pilon, Pierre; Hendrikse, Jan; Wilson, Derek J

    2014-11-04

    Ion mobility spectroscopy (IMS)-based trace-compound detectors (TCDs) are powerful and widely implemented tools for the detection of illicit substances. They combine high sensitivity, reproducibility, rapid analysis time, and resistance to dirt with an acceptable false alarm rate. The analytical specificity of TCD-IMS instruments for a given analyte depends strongly on a detailed knowledge of the ion chemistry involved, as well as the ability to translate this knowledge into field-robust analytical methods. In this work, we introduce an enhanced hybrid TCD-IMS/mass spectrometer (TCD-IMS/MS) that combines the strengths of ion-mobility-based target compound detection with unambiguous identification by tandem MS. Building on earlier efforts along these lines (Kozole et al., Anal. Chem. 2011, 83, 8596-8603), the current instrument is capable of positive and negative-mode analyses with tightly controlled gating between the IMS and MS modules and direct measurement of ion mobility profiles. We demonstrate the unique capabilities of this instrument using four samples of opium seized by the Canada Border Services Agency (CBSA), consisting of a mixture of opioid alkaloids and other naturally occurring compounds typically found in these samples. Although many analytical methods have been developed for analyzing naturally occurring opiates, this is the first detailed ion mobility study on seized opium samples. This work demonstrates all available analytical modes for the new IMS-MS system including "single-gate", "dual-gate", MS/MS, and precursor ion scan methods. Using a combination of these modes, we unambiguously identify all signals in the IMS spectra, including previously uncharacterized minor peaks arising from compounds that are common in raw opium.

  15. Development, optimization, and validation of a novel extraction procedure for the removal of opiates from human hair's surface.

    Science.gov (United States)

    Restolho, José; Barroso, Mário; Saramago, Benilde; Dias, Mário; Afonso, Carlos A M

    2015-05-01

    Room temperature ionic liquids (ILs) have proved to be efficient extraction media for several systems, and their ability to capture volatile compounds from the atmosphere is well established. We report herein a contactless extraction procedure for the removal of opiate drugs from the surface of human hair. The compounds were chosen as a model drug, particularly due to their low volatility. Equal amounts of IL and hair (about 100 mg) were introduced in a customized Y-shaped vial, and the process occurred simply by heating. After testing several ILs, some of them (e.g. 1-methyl-3-ethanol-imidazolium tetrafluoroborate, phenyl-trimethyl-ammonium triflate or bis(dimethyl) diheptylguanidinium iodide) showed extraction efficiencies higher than 80% for the two studied compounds, morphine and 6-monoacetylmorphine. Using the design of experiments (DOE) approach as an optimization tool, and bearing in mind the hygroscopic properties of the ILs (in particular, 1-methyl-3-ethanol-imidazolium tetrafluoroborate), the process was optimized concerning the following variables: temperature (50-120 ºC), extraction time (8-24 h), IL amount (50-200 mg) and water content of the IL (0.01-60%). This study not only provided the optimum conditions for the process (120 ºC, 16 h, 100 mg of IL containing 40% of water), but has also showed that the water content of the IL represents the variable with the most significant effect on the extraction efficiency. Finally, we validated our method through the comparison of the results obtained by treating hair samples with the described procedure to those obtained using a standard washing method and criteria for positivity.

  16. Alpha2C-adrenoceptor Del322-325 polymorphism and risk of psychiatric disorders: significant association with opiate abuse and dependence.

    Science.gov (United States)

    Rivero, Guadalupe; Martín-Guerrero, Idoia; de Prado, Elena; Gabilondo, Ane M; Callado, Luis F; García-Sevilla, Jesús A; García-Orad, África; Meana, J Javier

    2016-06-01

    Objectives α2C-adrenoceptors (α2C-AR) are involved in behavioural responses relevant to psychiatric disorders and suicide completion. The genetic polymorphism α2CDel322-325-AR confers a loss-of-function phenotype. Functional human studies have associated α2CDel322-325-AR polymorphism with major depression pathophysiology. The aim of this study was to analyse, for the first time, the association of α2CDel322-325-AR polymorphism with suicide completion and with related psychiatric disorders: major depression, schizophrenia, opiate and alcohol abuse and dependence. Methods Post-mortem brain DNA was extracted (n = 516) and genotyping performed by HaeIII restriction endonuclease digestion of PCR products and DNA fragment analysis on capillary sequencer. Amplified products were sequenced to confirm the presence of the polymorphism. Results The frequency of α2CDel322-325-AR in suicide (9%, n = 236) and non-suicide victims (11%, n = 280) was similar. Genotype frequencies for the α2CDel322-325-AR polymorphism in depressed (15%, n = 39) and schizophrenic subjects (18%, n = 39) were higher than in controls (7%, n = 187), but these differences did not reach statistical significance (P = 0.125 and P = 0.063, respectively). A selective and significant association of α2CDel322-325-AR polymorphism with opiate abuse and dependence was found (23%, n = 35, P = 0.011). Conclusions Our results indicate that α2CDel322-325-AR may play a role in the pathophysiology of opiate abuse and dependence and raise the interest for larger genetic associative studies.

  17. Direct and efficient liquid chromatographic-tandem mass spectrometric method for opiates in urine drug testing - importance of 6-acetylmorphine and reduction of analytes.

    Science.gov (United States)

    Andersson, Maria; Stephanson, Nikolai; Ohman, Inger; Terzuoli, Tommy; Lindh, Jonatan D; Beck, Olof

    2014-04-01

    Opiates comprise a class of abused drugs that is of primary interest in clinical and forensic urine drug testing. Determination of heroin, codeine, or a multi-drug ingestion is complicated since both heroin and codeine can lead to urinary excretion of free and conjugated morphine. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) offers advantage over gas chromatography-mass spectrometry by simplifying sample preparation but increases the number of analytes. A method based on direct injection of five-fold diluted urine for confirmation of morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine, codeine-6-glucuronide and 6-acetylmorphine was validated using LC-MS/MS in positive electrospray mode monitoring two transitions using selected reaction monitoring. The method was applied for the analysis of 3155 unknown urine samples which were positive for opiates in immunochemical screening. A linear response was observed for all compounds in the calibration curves covering more than three orders of magnitude. Cut off was set to 2 ng/ml for 6-acetylmorphine and 150 ng/ml for the other analytes. 6-Acetylmorphine was found to be effective (sensitivity 82%) in detecting samples as heroin intake. Morphine-3-glucuronide and codeine-6-glucuronide was the predominant components of total morphine and codeine, 84% and 93%, respectively. The authors have validated a robust LC-MS/MS method for rapid qualitative and quantitative analysis of opiates in urine. 6-Acetylmorphine has been demonstrated as a sensitive and important parameter for a heroin intake. A possible interpretation strategy to conclude the source of detected analytes was proposed. The method might be further developed by reducing the number of analytes to morphine-3-glucuronide, codeine-6-glucuronide and 6-acetylmorphine without compromising test performance.

  18. Decreased mitochondrial DNA copy number in the hippocampus and peripheral blood during opiate addiction is mediated by autophagy and can be salvaged by melatonin.

    Science.gov (United States)

    Feng, Yue-Mei; Jia, Yun-Fang; Su, Ling-Yan; Wang, Dong; Lv, Li; Xu, Lin; Yao, Yong-Gang

    2013-09-01

    Drug addiction is a chronic brain disease that is a serious social problem and causes enormous financial burden. Because mitochondrial abnormalities have been associated with opiate addiction, we examined the effect of morphine on mtDNA levels in rat and mouse models of addiction and in cultured cells. We found that mtDNA copy number was significantly reduced in the hippocampus and peripheral blood of morphine-addicted rats and mice compared with control animals. Concordantly, decreased mtDNA copy number and elevated mtDNA damage were observed in the peripheral blood from opiate-addicted patients, indicating detrimental effects of drug abuse and stress. In cultured rat pheochromocytoma (PC12) cells and mouse neurons, morphine treatment caused many mitochondrial defects, including a reduction in mtDNA copy number that was mediated by autophagy. Knockdown of the Atg7 gene was able to counteract the loss of mtDNA copy number induced by morphine. The mitochondria-targeted antioxidant melatonin restored mtDNA content and neuronal outgrowth and prevented the increase in autophagy upon morphine treatment. In mice, coadministration of melatonin with morphine ameliorated morphine-induced behavioral sensitization, analgesic tolerance and mtDNA content reduction. During drug withdrawal in opiate-addicted patients and improvement of protracted abstinence syndrome, we observed an increase of serum melatonin level. Taken together, our study indicates that opioid addiction is associated with mtDNA copy number reduction and neurostructural remodeling. These effects appear to be mediated by autophagy and can be salvaged by melatonin.

  19. Productive infection of human neural progenitor cells by R5 tropic HIV-1: opiate co-exposure heightens infectivity and functional vulnerability

    Science.gov (United States)

    Balinang, Joyce M.; Masvekar, Ruturaj R.; Hauser, Kurt F.; Knapp, Pamela E.

    2017-01-01

    Objective HIV type-1 (HIV-1) causes a spectrum of central nervous system (CNS) complications; many are worsened by opiate co-exposure. Human neural progenitor cells (hNPCs) give rise to all CNS neurons and macroglia. We tested the hypothesis that hNPC maturation and fate are altered by HIV and opiates, contributing to HIV-1-related neuropathology. Reports of hNPC infection remain controversial. We rigorously examined this question, testing whether hNPC propagated infection and whether HIV affected hNPCs absent their infection. Design and methods Primary hNPCs were characterized over multiple passages. Following R5 HIV-1BaL exposure, p24, Nef, and tat assays monitored infection; a serial dilution approach tested infection transfer to naive hNPCs. Bromodeoxyuridine uptake, population doubling time, and immunostaining assessed proliferation and differentiation. Morphine co-exposure assessed opiate interactions. Supernatant from HIV-1BaL-infected PBMCs (HIVsup), HIV-1BaL, and ultraviolet light-inactivated HIVsup were compared to test effects of inflammatory milieu versus virus or infection per se. Results The hNPCs (CD4_/CD8_/Iba_/CXC3CL1_/CD11b_) were infectable and could transfer infection to naive hNPCs. Infection was partly blocked by maraviroc, implicating CCR5. HIVsup reduced hNPC proliferation and caused premature differentiation into neurons/astroglia. Effects on proliferation were due to soluble factors/viral proteins, not infection per se. Morphine co-exposure exacerbated certain functional consequences of HIVsup, and sustained the infection of hNPCs. Conclusion hNPCs can be infected and propagate virus in vitro. hNPCs or their progeny may represent an underappreciated viral reservoir. Factors from infected cells alter hNPC proliferation and neural cell maturation which likely compromises CNS structure and function. Morphine–HIV interactions may worsen dysfunction and sustain infection. PMID:28099189

  20. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

    2003-01-01

    therefore been acknowledged to be a third endogenous ligand at SRIF receptors. This review goes through mechanisms of signal transduction, pharmacology, and anatomical distribution of SRIF receptors. Structurally, SRIF receptors belong to the superfamily of G protein-coupled (GPC) receptors, sharing....... The generation of knock-out (KO) mice, intended as a means to define the contributions made by individual receptor subtypes, necessarily marks but an approximation. Furthermore, we must now take into account the stunning complexity of receptor co-operation indicated by the observation of receptor homo......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

  1. S-Nitrosothiols modulate G protein-coupled receptor signaling in a reversible and highly receptor-specific manner

    Directory of Open Access Journals (Sweden)

    Mönkkönen Kati S

    2005-04-01

    Full Text Available Abstract Background Recent studies indicate that the G protein-coupled receptor (GPCR signaling machinery can serve as a direct target of reactive oxygen species, including nitric oxide (NO and S-nitrosothiols (RSNOs. To gain a broader view into the way that receptor-dependent G protein activation – an early step in signal transduction – might be affected by RSNOs, we have studied several receptors coupling to the Gi family of G proteins in their native cellular environment using the powerful functional approach of [35S]GTPγS autoradiography with brain cryostat sections in combination with classical G protein activation assays. Results We demonstrate that RSNOs, like S-nitrosoglutathione (GSNO and S-nitrosocysteine (CysNO, can modulate GPCR signaling via reversible, thiol-sensitive mechanisms probably involving S-nitrosylation. RSNOs are capable of very targeted regulation, as they potentiate the signaling of some receptors (exemplified by the M2/M4 muscarinic cholinergic receptors, inhibit others (P2Y12 purinergic, LPA1lysophosphatidic acid, and cannabinoid CB1 receptors, but may only marginally affect signaling of others, such as adenosine A1, μ-opioid, and opiate related receptors. Amplification of M2/M4 muscarinic responses is explained by an accelerated rate of guanine nucleotide exchange, as well as an increased number of high-affinity [35S]GTPγS binding sites available for the agonist-activated receptor. GSNO amplified human M4 receptor signaling also under heterologous expression in CHO cells, but the effect diminished with increasing constitutive receptor activity. RSNOs markedly inhibited P2Y12 receptor signaling in native tissues (rat brain and human platelets, but failed to affect human P2Y12 receptor signaling under heterologous expression in CHO cells, indicating that the native cellular signaling partners, rather than the P2Y12 receptor protein, act as a molecular target for this action. Conclusion These in vitro studies

  2. Psychiatric comorbidity differences between women with history of childhood sexual abuse who are methadone-maintained former opiate addicts and non-addicts.

    Science.gov (United States)

    Peles, Einat; Adelson, Miriam; Seligman, Zivya; Bloch, Miki; Potik, David; Schreiber, Shaul

    2014-09-30

    Following our finding of high rates of obsessive compulsive disorder (OCD) among methadone maintained (MMT) former opiate addict women with a history of childhood sexual abuse, we compared 68 MMT sexually abused women to 48 women from a Sexual Abuse Treatment Center (SATC) without a history of opiate addiction, for clinical-OCD (Yale-Brown Obsessive Compulsive Scale), dissociation (Dissociative Experiences Scale (DES), complex-post-traumatic stress disorder (PTSD) (Structured Interview for Disorders of Extreme Stress - Non-Other Specify), sexual PTSD (the Clinician-Administered PTSD Scale) and trauma events history (Life Event Inventory). MMT patients were treated for longer periods and were older and less educated. Clinical OCD was more prevalent among the MMT patients (66.2% vs. 30.4%, respectively), while complex-PTSD and high dissociation score (DES≥30) were more prevalent among the non-addicts (46.9% vs. 19.1%, and 57.1% vs. 11.8% respectively). The high rate of OCD among sexually abused MMT women was not found in women who are sexually abused non-addicts. As dissociation was rare among the MMT group, it may just be that the opioids (either as street-drugs or as MMT) serve as an external coping mechanism when the access to the internal one is not possible. Future study about OCD and dissociation before entry to MMT are needed.

  3. [Low-threshold primary care for patients in opiate maintenance therapy. A pilot project in Malmö, Sweden, integrates primary care and OMT].

    Science.gov (United States)

    Dahlman, Disa; Palm, Åsa; Sunesdotter, Christina; Troberg, Katja; Wallin, Camilla

    2016-10-14

    Low-threshold primary care for patients in opiate maintenance therapy. A pilot project in Malmö, Sweden, integrates primary care and OMT  This report illustrates how integration of primary care and opiate maintenance therapy (OMT) may improve OMT patients health and minimize obstacles for care seeking. OMT patients have poor health. Around 80 % have hepatitis C, a majority smoke tobacco, and socio-economic status is generally low. However, somatic health is often under-prioritized in this group. To improve OMT patients physical health', two OMT clinics and one primary care center in Malmö, Sweden, started a pilot project in 2014. This project includes: OMT personnel suggest their patients to see a primary care physician and assist with booking; Primary care physicians interested in and/or experienced from addiction care; Closer contact between primary care and OMT, regarding initiated medication, recommended follow-up, referrals, etc. Patients and care givers stress the importance of easily accessible care for this vulnerable patient group. To scientifically evaluate such projects, controlled studies are necessary.

  4. Determination of opiates in whole blood and vitreous humor: a study of the matrix effect and an experimental design to optimize conditions for the enzymatic hydrolysis of glucuronides.

    Science.gov (United States)

    Sanches, Livia Rentas; Seulin, Saskia Carolina; Leyton, Vilma; Paranhos, Beatriz Aparecida Passos Bismara; Pasqualucci, Carlos Augusto; Muñoz, Daniel Romero; Osselton, Michael David; Yonamine, Mauricio

    2012-04-01

    Undoubtedly, whole blood and vitreous humor have been biological samples of great importance in forensic toxicology. The determination of opiates and their metabolites has been essential for better interpretation of toxicological findings. This report describes the application of experimental design and response surface methodology to optimize conditions for enzymatic hydrolysis of morphine-3-glucuronide and morphine-6-glucuronide. The analytes (free morphine, 6-acetylmorphine and codeine) were extracted from the samples using solid-phase extraction on mixed-mode cartridges, followed by derivatization to their trimethylsilyl derivatives. The extracts were analysed by gas chromatography-mass spectrometry with electron ionization and full scan mode. The method was validated for both specimens (whole blood and vitreous humor). A significant matrix effect was found by applying the F-test. Different recovery values were also found (82% on average for whole blood and 100% on average for vitreous humor). The calibration curves were linear for all analytes in the concentration range of 10-1,500 ng/mL. The limits of detection ranged from 2.0 to 5.0 ng/mL. The method was applied to a case in which a victim presented with a previous history of opiate use.

  5. The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS prisons project pilot study: protocol for a randomised controlled trial comparing dihydrocodeine and buprenorphine for opiate detoxification

    Directory of Open Access Journals (Sweden)

    Dalton Richard

    2007-01-01

    Full Text Available Abstract Background In the United Kingdom (UK, there is an extensive market for the class 'A' drug heroin. Many heroin users spend time in prison. People addicted to heroin often require prescribed medication when attempting to cease their drug use. The most commonly used detoxification agents in UK prisons are buprenorphine, dihydrocodeine and methadone. However, national guidelines do not state a detoxification drug of choice. Indeed, there is a paucity of research evaluating the most effective treatment for opiate detoxification in prisons. This study seeks to address the paucity by evaluating routinely used interventions amongst drug using prisoners within UK prisons. Methods/Design The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS Prisons Pilot Study will use randomised controlled trial methodology to compare the open use of buprenorphine and dihydrocodeine for opiate detoxification, given in the context of routine care, within HMP Leeds. Prisoners who are eligible and give informed consent will be entered into the trial. The primary outcome measure will be abstinence status at five days post detoxification, as determined by a urine test. Secondary outcomes during the detoxification and then at one, three and six months post detoxification will be recorded.

  6. Development and validation of a single LC-MS/MS assay following SPE for simultaneous hair analysis of amphetamines, opiates, cocaine and metabolites.

    Science.gov (United States)

    Imbert, L; Dulaurent, S; Mercerolle, M; Morichon, J; Lachâtre, G; Gaulier, J-M

    2014-01-01

    The two major challenges in hair analysis are the limited amount of samples usually available and the low targeted concentrations. To overcome these limitations, a liquid chromatography-electrospray-tandem mass spectrometry method (LC-ESI-MS/MS) allowing the simultaneous analysis of 17 amphetamines (amphetamine, BDB, m-CPP, dexfenfluramine, DOB, DOM, ephedrine, MBDB, MDA, MDEA, MDMA, methamphetamine, methylphenidate, 4-MTA, norephedrine, norfenfluramine and PMA), 5 opiates (morphine, codeine, heroin, ethylmorphine, and 6AM), cocaine and 5 metabolites [ecgonine methyl ester (EME), benzoylecgonine (BZE), anhydroecgonine methyl ester (AME), cocaethylene, and norcocaine] has been developed. The validation procedure included linearity, intra-day and inter-day variability and accuracy for 5 days (5 replicates at 3 concentration levels). Proficiency studies were used to check the accuracy of the method. As a result, all amphetamines, opiates and cocaine derivatives were satisfactory identified by 2 MRM transitions in 15 min. Calibration curves were performed by a quadratic 1/X weighted regression. The calibration model fits from 0.05 to 10 ng/mg. The limits of detection (LODs) range between 0.005 and 0.030 ng/mg. Precision has been checked by intra-day and inter-day RSD, and associated relative bias, which were lower than 25% for the limits of quantifications (LOQs) and lower than 20% for the other levels tested. This method was routinely applied to hair samples: two positive results of adult drug addicts are presented.

  7. The Effectiveness of Cognitive-Behavioral Group Therapy on Reduction of Craving, Depression and Anxiety Symptoms among the Opiate Abusers Under MMT

    Directory of Open Access Journals (Sweden)

    Fereshtwh Momeni

    2009-10-01

    Full Text Available Introduction: The aim of this study was to examine the effectiveness of cognitive behavior group therapy on reduction of craving, depression and anxiety symptoms among the Opiate abusers under MMT. Method: In this experimental research, 36 addicts on MMT were selected between the entire opiate addicts referred to Iranian national center for addiction studies (INCAS by convenience sampling and were randomly assigned into experimental and control groups. In experimental group, cognitive behavior group therapy was performed in 8 sessions, one each week. Sessions were performed for craving, depression and anxiety management. Data was gathered by demographic questionnaire, scale of relapse predicts craving assessment, BDI-II and BAI for depression and anxiety symptoms assessment. The data was analyzed, independent and paired samples t test. Results: Data analysis revealed that craving index was decreased in post- test and follow-up and it was statistically significant. Also beck depression and anxiety symptoms were decreased significantly in post-test and follow-up. Conclusion: The results show that cognitive-behavior group therapy was efficient on reduction of drug craving, depression, and anxiety symptoms in post-test and follow-up, and it can apply as a method of treatment.

  8. Evaluation of the Counter-regulatory Responses to Hypoglycemia in Patients with Type 1 Diabetes during Opiate Receptor Blockade with Naltrexone

    DEFF Research Database (Denmark)

    Naik, Sarita; Belfort-DeAguiar, Renata; Sejling, Anne-Sophie

    2016-01-01

    with a high risk for hypoglycemia. MATERIALS AND METHODS: We performed a randomized, placebo-controlled, double-blinded, cross-over study in which 9 intensively treated subjects with T1DM underwent a 2-step euglycemic-hypoglycemic-hyperinsulinemic clamp on two separate occasions. Twelve hours and 1 hour...

  9. The probability distribution of side-chain conformations in [Leu] and [Met]enkephalin determines the potency and selectivity to mu and delta opiate receptors

    DEFF Research Database (Denmark)

    Nielsen, Bjørn Gilbert; Jensen, Morten Østergaard; Bohr, Henrik

    2003-01-01

    The structure of enkephalin, a small neuropeptide with five amino acids, has been simulated on computers using molecular dynamics. Such simulations exhibit a few stable conformations, which also have been identified experimentally. The simulations provide the possibility to perform cluster analysis...... in the space defined by potentially pharmacophoric measures such as dihedral angles, side-chain orientation, etc. By analyzing the statistics of the resulting clusters, the probability distribution of the side-chain conformations may be determined. These probabilities allow us to predict the selectivity...

  10. Subgroups Among Opiate Addicts

    Science.gov (United States)

    Berzins, Juris I.; And Others

    1974-01-01

    The principal objective of the present investigation was to delineate homogeneous MMPI profile subgroups (types) through multivariate clustering procedures and to compare the derived (replicable) types on measures of the components of "sociopathy" as well as on other psychometric devices. (Author)

  11. Subgroups Among Opiate Addicts

    Science.gov (United States)

    Berzins, Juris I.; And Others

    1974-01-01

    The principal objective of the present investigation was to delineate homogeneous MMPI profile subgroups (types) through multivariate clustering procedures and to compare the derived (replicable) types on measures of the components of "sociopathy" as well as on other psychometric devices. (Author)

  12. Calcitonin receptors in the rat mesencephalon mediate its analgesic actions: autoradiographic and behavioral analyses

    Energy Technology Data Exchange (ETDEWEB)

    Fabbri, A.; Pert, C.B.; Pert, A.; Fraioli, F.

    1985-09-23

    Autoradiographic analyses of salmon calcitonin (sCT) binding in the rat mesencephalon revealed an exceptionally high concentration of receptors in the ventral and ventrolateral segments of the periaqueductal gray matter (PAG) extending along the entire rostralcaudal axis. Relatively heavy labeling was also seen along a band extending ventrolaterally through the mesencephalic reticular formation. Other receptor-rich areas include the nucleus linearis, pars compacta and lateralis of the substantia nigra, locus coeruleus, parabrachial nuclei and nucleus raphe pontis of the pontine reticular formation. The biological effects are consistent with the potencies of both peptides in displacing SVI-sCT from slide-mounted sections of rat PAG. Naloxone failed to antagonize sCT-induced analgesia, suggesting an opiate independent mechanism for this peptide in elicting analgesia. (Auth.). 60 refs.; 9 figs.

  13. Rats that binge eat fat-rich food do not show somatic signs or anxiety associated with opiate-like withdrawal: implications for nutrient-specific food addiction behaviors.

    Science.gov (United States)

    Bocarsly, Miriam E; Berner, Laura A; Hoebel, Bartley G; Avena, Nicole M

    2011-10-24

    Previous studies suggest that binge eating sugar leads to behavioral and neurochemical changes similar to those seen with drug addiction, including signs of opiate-like withdrawal. Studies are emerging that show multiple neurochemical and behavioral indices of addiction when animals overeat a fat-rich diet. The goal of the present study was to utilize liquid and solid diets high in sugar and fat content to determine whether opiate-like withdrawal is seen after binge consumption of these diets in Sprague-Dawley rats. Control groups were given ad libitum access to the sweet-fat food or standard chow. All rats were then given a battery of tests to measure signs of opiate-like withdrawal, which included somatic signs of distress, elevated plus-maze anxiety, and locomotor hypoactivity. Neither naloxone-precipitated (3 mg/kg) nor deprivation-induced withdrawal was observed in rats that were maintained on a nutritionally complete pelleted sweet-fat diet or a sweet, high-fat diet supplemented with standard rodent chow. Naloxone-precipitated withdrawal was also not seen in rats fed a liquid sweet-fat food. Further, body weight reduction to 85%, which is known to potentiate the reinforcing effects of substances of abuse, did not affect naloxone-precipitated signs of opiate-like withdrawal. Thus, unlike previous findings reported regarding rats with binge access to a sucrose solution, rats that binge eat sweet-fat combinations do not show signs of opiate-like withdrawal under the conditions tested. These data support the idea that excessive consumption of different nutrients can induce behaviors associated with addiction in different ways, and that the behaviors that could characterize "food addiction" may be subtyped based on the nutritional composition of the food consumed.

  14. Respiratory health screening for opiate misusers in a specialist community clinic: a mixed-methods pilot study, with integrated staff and service user feedback

    Science.gov (United States)

    Mitchell, Caroline Anne; Pitt, Alice; Hulin, Joe; Lawson, Rod; Ashby, Fleur; Appelqvist, Ivan; Delaney, Brigitte

    2016-01-01

    Objectives Increased rates of illicit drug inhalation are thought to expose opiate misusers (OMUs) to an enhanced risk of respiratory health problems. This pilot study aimed to determine the feasibility of undertaking respiratory screening of OMUs in a community clinic. Setting Single-centre UK community substance misuse clinic. Participants All clinic attendees receiving treatment for opiate misuse were eligible to participate. 36 participants (mean age=37) were recruited over a 5-week period. The sample included 26 males and 10 females. Outcome measures Spirometry without bronchodilation; health related quality of life EQ-5D-3L; Asthma Control Test; Mini Asthma Quality of Life; Clinical COPD Questionnaire and the Treatment Outcome Profile were used to assess the respiratory health of participants. Findings were discussed with staff and service users in 2 patient and public involvement events and feedback was analysed thematically. Results 34 participants reported that they had smoked heroin. 8 participants diagnosed with asthma, scored under 13 on the Asthma Control Test, suggesting poorly controlled asthma. Participants (n=28), without a diagnosis of asthma completed the Lung Function Questionnaire. Of these, 79% produced scores under 18, indicating symptoms associated with the development of chronic obstructive pulmonary disease. Spirometry showed 14% of all participants had forced expiratory volume in 1 s/forced vital capacity <0.7 (without bronchodilator), indicating potential obstructive lung disease. Feedback from service users and staff suggested a willingness and capacity to deliver respiratory health screening programmes. Insight towards the difficulties service users have in accessing services and the burden of respiratory health was also provided. Conclusions It is feasible to undertake respiratory health screening of OMUs in a community clinic. Larger screening studies are warranted to determine the prevalence of respiratory health problems in this

  15. HIV-related cognitive impairment shows bi-directional association with dopamine receptor DRD1 and DRD2 polymorphisms in substance-dependent and substance-independent populations.

    Science.gov (United States)

    Jacobs, Michelle M; Murray, Jacinta; Byrd, Desiree A; Hurd, Yasmin L; Morgello, Susan

    2013-10-01

    It has been postulated that drugs of abuse act synergistically with HIV, leading to increased neurotoxicity and neurocognitive impairment. The CNS impacts of HIV and drug use converge on the mesocorticolimbic dopamine (DA) system, which contains two main receptor subtypes: dopamine receptors 1 (DRD1) and 2 (DRD2). DRD1 and DRD2 have been linked to substance dependence; whether they predict HIV-associated neurocognitive disorder (HAND) is unclear. Using an advanced-stage HIV+ population, we sought to determine if drug dependence impacts the contribution of DA receptor polymorphisms on neurocognition. We observed that both DRD1 and DRD2 polymorphisms were associated with opiate and cocaine dependence (P opiate and cocaine dependency. In the Motor domain, we observed an association for two DRD2 polymorphisms (P < 0.05) in Caucasian subjects. The effects differed for substance dependence groups as the direction of the correlations with DRD2 were opposite to what was seen in subjects without these dependencies. In African-American subjects, associations were observed in nearly every domain, and again, the direction of the correlation differed between substance-dependent and substance-independent groups. We conclude that studies to examine genetic risk for HAND must carefully account for substance dependence patterns when assaying dopaminergic systems, as the neurobiological substrates of cognition in HIV populations may vary with tonic alterations secondary to chronic substance exposures.

  16. Spinal Tolerance and Dependence: Some Observations on the Role of Spinal N-Methyl-D-Aspartate Receptors and Phosphorylation in the Loss of Opioid Analgesic Responses

    Directory of Open Access Journals (Sweden)

    Tony L Yaksh

    2000-01-01

    Full Text Available The continuous delivery of opiates can lead to a reduction in analgesic effects. In humans, as in other animals, some component of this change in sensitivity seems likely to have a strong pharmacodynamic component. Such loss of effect, deemed to be tolerance in the present article, can be readily demonstrated in animals with repeated bolus and continuous intrathecal infusion of mu and delta opioids and alpha-2 adrenergic agonists. Research has shown that this loss of effect can be diminished by concurrent treatment with N-methyl-D-aspartate (NMDA receptor antagonists and by the suppression of the activity of spinal protein kinase C (PKC. This suggests in part the probable role of PKC-mediated phosphorylation in the right shift in the dose-effect curves observed with continuous opiate or adrenergic exposure. Importantly, this right shift is seen to occur in parallel with an increase in the phosphorylating activity in the dorsal horn and in the expression of several PKC isozymes. The target of this phosphorylation is not certain. Phosphorylation of the NMDA receptor enhances its functionality, while phosphorylation of the opioid receptor or associated channels seems to diminish their activity or to enhance internalization. While the focus is on several specific components, the accumulating data emphasize the biological complexity of these changes in spinal drug reactivity.

  17. Effects of chronic delta-9-tetrahydrocannabinol (THC) administration on neurotransmitter concentrations and receptor binding in the rat brain.

    Science.gov (United States)

    Ali, S F; Newport, G D; Scallet, A C; Gee, K W; Paule, M G; Brown, R M; Slikker, W

    1989-01-01

    THC is the major psychoactive constituent of marijuana and is also known as an hallucinogenic compound. Numerous reports have shown that large doses of THC produce significant alterations in various neurotransmitter systems. The present study was designed to determine whether chronic exposure to THC produces significant alterations in selected neurotransmitter systems (dopamine, serotonin, acetylcholine, GABAergic, benzodiazepine, and opiate) in the rat brain. In Experiment 1, male Sprague-Dawley rats were gavaged with vehicle, 10 or 20 mg THC/kg body weight daily, 5 days/week for 90 days. Animals were killed either 24 hours or two months after the last dose. Brains were dissected into different regions for neurochemical analyses. Two months after the cessation of chronic administration, there was a significant decrease in GABA receptor binding in the hippocampus of animals in the high dose group. However, no other significant changes were found in neurotransmitter receptor binding characteristics in the hippocampus or in neurotransmitter concentrations in the caudate nucleus, hypothalamus or septum after chronic THC administration. In an attempt to replicate the GABA receptor binding changes and also to determine the [35S]TBPS binding in hippocampus, we designed Experiment 2. In this experiment, we dosed the animals by gavage with 0, 5, 10 or 20 mg THC/kg daily, 5 days/week or with 20 mg THC/kg Monday through Thursday and 60 mg/kg on Friday for 90 days. Results from this experiment failed to replicate the dose-dependent effect of THC on GABA receptor binding in hippocampus. Modulation of [35S]TBPS binding by GABA or 3 alpha-OH-DHP or inhibition by cold TBPS in frontal cortex did not show any significant dose-related effects. Results from these experiments suggest that chronic exposure to THC does not produce significant alterations in catecholamine or indoleamine neurotransmitter systems or in opiate or GABA receptor systems in the rat brain.

  18. Lipoxin Receptors

    Directory of Open Access Journals (Sweden)

    Mario Romano

    2007-01-01

    Full Text Available Lipoxins (LXs represent a class of arachidonic acid (AA metabolites that carry potent immunoregulatory and anti-inflammatory properties, LXA4 and LXB4 being the main components of this series. LXs are generated by cooperation between 5-lipoxygenase (LO and 12- or 15-LO during cell-cell interactions or by single cell types. LX epimers at carbon 15, the 15-epi-LXs, are formed by aspirin-acetylated cyclooxygenase-2 (COX-2 in cooperation with 5-LO. 15-epi-LXA4 is also termed aspirin-triggered LX (ATL. In vivo studies with stable LX and ATL analogs have established that these eicosanoids possess potent anti-inflammatory activities. A LXA4 receptor has been cloned. It belongs to the family of chemotactic receptors and clusters with formyl peptide receptors on chromosome 19. Therefore, it was initially denominated formyl peptide receptor like 1 (FPRL1. This receptor binds with high affinity and stereoselectivity LXA4 and ATL. It also recognizes a variety of peptides, synthetic, endogenously generated, or disease associated, but with lower affinity compared to LXA4. For this reason, this receptor has been renamed ALX. This review summarizes the current knowledge on ALX expression, signaling, and potential pathophysiological role. The involvement of additional recognition sites in LX bioactions is also discussed.

  19. Abnormal nociception and opiate sensitivity of STOP null mice exhibiting elevated levels of the endogenous alkaloid morphine

    Directory of Open Access Journals (Sweden)

    Aunis Dominique

    2010-12-01

    Full Text Available Abstract Background- Mice deficient for the stable tubule only peptide (STOP display altered dopaminergic neurotransmission associated with severe behavioural defects including disorganized locomotor activity. Endogenous morphine, which is present in nervous tissues and synthesized from dopamine, may contribute to these behavioral alterations since it is thought to play a role in normal and pathological neurotransmission. Results- In this study, we showed that STOP null brain structures, including cortex, hippocampus, cerebellum and spinal cord, contain high endogenous morphine amounts. The presence of elevated levels of morphine was associated with the presence of a higher density of mu opioid receptor with a higher affinity for morphine in STOP null brains. Interestingly, STOP null mice exhibited significantly lower nociceptive thresholds to thermal and mechanical stimulations. They also had abnormal behavioural responses to the administration of exogenous morphine and naloxone. Low dose of morphine (1 mg/kg, i.p. produced a significant mechanical antinociception in STOP null mice whereas it has no effect on wild-type mice. High concentration of naloxone (1 mg/kg was pronociceptive for both mice strain, a lower concentration (0.1 mg/kg was found to increase the mean mechanical nociceptive threshold only in the case of STOP null mice. Conclusions- Together, our data show that STOP null mice displayed elevated levels of endogenous morphine, as well as an increase of morphine receptor affinity and density in brain. This was correlated with hypernociception and impaired pharmacological sensitivity to mu opioid receptor ligands.

  20. Mu Opioid Receptors in Gamma-Aminobutyric Acidergic Forebrain Neurons Moderate Motivation for Heroin and Palatable Food.

    Science.gov (United States)

    Charbogne, Pauline; Gardon, Olivier; Martín-García, Elena; Keyworth, Helen L; Matsui, Aya; Mechling, Anna E; Bienert, Thomas; Nasseef, Taufiq; Robé, Anne; Moquin, Luc; Darcq, Emmanuel; Ben Hamida, Sami; Robledo, Patricia; Matifas, Audrey; Befort, Katia; Gavériaux-Ruff, Claire; Harsan, Laura-Adela; von Elverfeldt, Dominik; Hennig, Jurgen; Gratton, Alain; Kitchen, Ian; Bailey, Alexis; Alvarez, Veronica A; Maldonado, Rafael; Kieffer, Brigitte L

    2017-05-01

    Mu opioid receptors (MORs) are central to pain control, drug reward, and addictive behaviors, but underlying circuit mechanisms have been poorly explored by genetic approaches. Here we investigate the contribution of MORs expressed in gamma-aminobutyric acidergic forebrain neurons to major biological effects of opiates, and also challenge the canonical disinhibition model of opiate reward. We used Dlx5/6-mediated recombination to create conditional Oprm1 mice in gamma-aminobutyric acidergic forebrain neurons. We characterized the genetic deletion by histology, electrophysiology, and microdialysis; probed neuronal activation by c-Fos immunohistochemistry and resting-state functional magnetic resonance imaging; and investigated main behavioral responses to opiates, including motivation to obtain heroin and palatable food. Mutant mice showed MOR transcript deletion mainly in the striatum. In the ventral tegmental area, local MOR activity was intact, and reduced activity was only observed at the level of striatonigral afferents. Heroin-induced neuronal activation was modified at both sites, and whole-brain functional networks were altered in live animals. Morphine analgesia was not altered, and neither was physical dependence to chronic morphine. In contrast, locomotor effects of heroin were abolished, and heroin-induced catalepsy was increased. Place preference to heroin was not modified, but remarkably, motivation to obtain heroin and palatable food was enhanced in operant self-administration procedures. Our study reveals dissociable MOR functions across mesocorticolimbic networks. Thus, beyond a well-established role in reward processing, operating at the level of local ventral tegmental area neurons, MORs also moderate motivation for appetitive stimuli within forebrain circuits that drive motivated behaviors. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Research on epidemiologlcal investigation of 4472 opiate dependence patients in Guangdong area%广东地区4472例阿片类药物依赖者流行病学调查

    Institute of Scientific and Technical Information of China (English)

    张伟杰; 刘锋; 李云贵; 吴培德; 陈海棠; 舒畅; 苏木金

    2011-01-01

    目的:了解广东地区阿片类药物依赖者流行病学特征,进一步做好阿片类药物依赖防治工作.方法:采用问卷调查,对2000年1月~2009年12月在解放军广州疗养院自愿戒毒中心住院的广东地区阿片类药物依赖者的资料进行分析.结果:本地区阿片类药物依赖者中90.52%为男性,29岁以下青少年占71.38%,职业为个体工商户占77.64%,初中及以下文化占84.27%.阿片类药物中海洛因占98.66%,吸毒方式中烫吸占46.88%,静脉注射占39.04%,引起并发症的占89.27%.传染性疾病占62.66%,乙肝、丙肝、艾滋病HIV阳性、性病、活动性肺结核分别占32.42%、24.02%、1.59%、2.77%、1.86%.结论:海洛因是广东地区阿片类药物依赖的主要类型,29岁以下的青少年是阿片类药物依赖的高危易感人群,吸毒方式主要是烫吸和静脉注射,吸毒人员合并的乙肝、丙肝、艾滋病等传染性疾病明显高于正常人群.%Objective: To study the epidemic characteristics of opiate dependence patients in Guangdong area, further improve the prevention and treatment of opiate dependence. Methods: Adopt questionnaire investigation, analysis was carried out among Guangdong area opiate dependence patients who were hospitalized in Guangzhou sanatorium voluntary detoxifi cation center of Chinese People's Liberation Army (PLA) from January 2000 to December 2009. Results: Opiate dependence patients in Guangdong area tended to be male (90.52%), young people aged below 29 years (71.38%), private entrepreneurs (77.64%) and 84.27% of those got only junior school or below education. Heroin (98.66%) was the major opiates abused. Inhalation and intravenous injection were the first two ways of administration (46.88% and 39.04%). Most of those had complications (89.27%), especially infectious complications (62.66%), such as viral hepatitis type B(32.42%), viral hepatitis C(24.02%), HIV positive(1.59%), sexually-transmitted disease (2

  2. YFa and analogs: Investigation of opioid receptors in smooth muscle contraction

    Institute of Scientific and Technical Information of China (English)

    Krishan Kumar; Ritika Goyal; Annu Mudgal; Anita Mohan; Santosh Pasha

    2011-01-01

    AIM: To study the pharmacological profile and inhibition of smooth muscle contraction by YFa and its analogs in conjunction with their receptor selectivity. METHODS: The effects of YFa and its analogs (D-Ala2) YFa, Y (D-Ala2) GFMKKKFMRF amide and Des-Phe- YGGFMKKKFMR amide in guinea pig ileum (GPI) and mouse vas deferens (MVD) motility were studied using an isolated tissue organ bath system, and morphine and DynA (1-13) served as controls. Acetylcholine was used for muscle stimulation. The observations were validated by specific antagonist pretreatment experiments using naloxonazine, naltrindole and norbinaltorphimine norBNI. RESULTS: YFa did not demonstrate significant inhibition of GPI muscle contraction as compared with morphine (15% vs 62%, P = 0.0002), but moderate inhibition of MVD muscle contraction, indicating the role of κ opioid receptors in the contraction. A moderate inhibition of GPI muscles by (Des-Phe) YFa revealed the role of anti-opiate receptors in the smooth muscle contraction. (D-Ala-2) YFa showed significant inhibition of smooth muscle contraction, indicating the involvement of mainly d receptors in MVD contraction. These results were supported by specific antagonist pretreatment assays. CONCLUSION: YFa revealed its side-effect-free analgesic properties with regard to arrest of gastrointestinal transit. The study provides evidences for the involvement of κ and anti-opioid receptors in smooth muscle contraction.

  3. Opioid Receptors.

    Science.gov (United States)

    Stein, Christoph

    2016-01-01

    Opioids are the oldest and most potent drugs for the treatment of severe pain. Their clinical application is undisputed in acute (e.g., postoperative) and cancer pain, but their long-term use in chronic pain has met increasing scrutiny. This article reviews mechanisms underlying opioid analgesia and other opioid actions. It discusses the structure, function, and plasticity of opioid receptors; the central and peripheral sites of analgesic actions and side effects; endogenous and exogenous opioid receptor ligands; and conventional and novel opioid compounds. Challenging clinical situations, such as the tension between chronic pain and addiction, are also illustrated.

  4. Comparison of prescriber evaluations and patient-directed self-reports in office-based practice for buprenorphine treatment of opiate-dependent individuals in France, 2002

    Directory of Open Access Journals (Sweden)

    Estelle Lavie

    2008-11-01

    Full Text Available Estelle Lavie1, Mélina Fatséas1, Jean-Pierre Daulouède1,2, Cécile Denis1, Jacques Dubernet1, Laurent Cattan3, Marc Auriacombe11Laboratoire de psychiatrie/EA4139, INSERM IFR-99 and Faculté de médecine Victor Pachon, University Victor Segalen Bordeaux 2, Bordeaux, France; 2Bizia, Centre de soins d’addictologie, Centre Hospitalier de la Côte Basque, Bayonne, France; 3Centre médical, Noisy-le-sec, FranceAbstract: The objective of this cross-sectional evaluation study was to compare data generated through prescriber assessments, and data generated from independent direct contact with opiate-dependent patients in office-based practice to evaluate buprenorphine treatment for modality of buprenorphine absorption, benzodiazepine use, and depressive symptoms. A group of buprenorphine office-based practice prescribers was selected to participate in this study. They were asked to screen for inclusion all their patients coming for a visit from February to August 2002. Once included by their prescribing physician, patients were given a series of self-administered questionnaires to be returned directly to the research staff, independently of their prescriber. Each prescriber was given a questionnaire to complete based on their knowledge and interview of the patient. Items assessed were history of current treatment, current substance use, buprenorphine treatment related behavior (daily frequency of intake, route of administration, benzodiazepine use and existence of a major depressive episode. Prescribers and patients’ questionnaires were compared. Concordance of both assessments was assessed by kappa statistics. The sensitivity and specificity as well as the positive and negative predictive values of prescriber collected information were compared to that of their patients’. There was an overall good correlation between both data sources on the procedures for buprenorphine use especially for intravenous use of buprenorphine. There were important

  5. Online extraction LC-MS/MS method for the simultaneous quantitative confirmation of urine drugs of abuse and metabolites: amphetamines, opiates, cocaine, cannabis, benzodiazepines and methadone.

    Science.gov (United States)

    de Jager, Andrew D; Bailey, Neville L

    2011-09-01

    A rapid LC-MS/MS method for confirmatory testing of five major categories of drugs of abuse (amphetamine-type substances, opiates, cocaine, cannabis metabolites and benzodiazepines) in urine has been developed. All drugs of abuse mandated by the Australian/New Zealand Standard AS/NZS 4308:2008 are quantified in a single chromatographic run. Urine samples are diluted with a mixture of isotope labelled internal standards. An on-line trap-and-flush approach, followed by LC-ESI-MS/MS has been successfully used to process samples in a functioning drugs of abuse laboratory. Following injection of diluted urine samples, compounds retained on the trap cartridge are flushed onto a reverse-phase C18 HPLC column (5-μm particle size) with embedded hydrophylic functionality. A total chromatographic run-time of 15 min is required for adequate resolution. Automated quantitation software algorithms have been developed in-house using XML scripting to partially automate the identification of positive samples, taking into account ion ratio (IR) and retention times (Rt). The sensitivity of the assay was found to be adequate for the quantitation of drugs in urine at and below the confirmation cut-off concentrations prescribed by AS/NZS 4308:2008.

  6. Dissociative disorders and possession experiences in Israel: a comparison of opiate use disorder patients, Arab women subjected to domestic violence, and a nonclinical group.

    Science.gov (United States)

    Somer, Eli; Ross, Colin; Kirshberg, Revital; Bakri, Rana Shawahdy; Ismail, Shefa

    2015-02-01

    This study examined the association between exposure to domestic violence and dissociative symptoms. A sample of 68 Israeli opiate use disorder patients in recovery, 80 battered Arab Israeli women, and 103 respondents from a community sample participated in structured interviews that included the Dissociative Disorders Interview Schedule (DDIS), the Dissociative Trance Disorder Interview Schedule (DTDIS), and the Dissociative Experiences Scale (DES). As predicted, community participants reported significantly less exposure to traumatizing events and lower levels of dissociative psychopathology than individuals sampled from specialized treatment centers. In all, 91% of battered female participants were taxon-positive for dissociative disorder with 1 of every 2 respondents reporting symptoms corresponding to dissociative amnesia and depersonalization disorder, suggesting that this group may be particularly vulnerable to dissociative psychopathology. Extrasensory and paranormal experiences (ESP) and dissociative trance disorder experiences were strongly related to dissociative experiences and features of dissociative identity disorder (DID). These statistical associations suggest that dissociative disorders and ESP/trance experiences may share an underlying construct. Further research is needed on trauma and dissociation among female victims of domestic abuse in patriarchal, collectivist societies, particularly in the Arab world. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  7. How can a methadone and an opiate-positive immunoassay result be reconciled in a patient prescribed only OxyContin and Wellbutrin?

    Science.gov (United States)

    Abadie, Jude M

    2013-01-01

    Appropriate management of patients in pain clinics can be complex and sometimes confusing because providers must correctly interpret multiple sources of patient information. The correct interpretation of laboratory results is essential to guide subsequent patient treatment and management; however, laboratory and clinical pictures can appear to be conflicting in cases of substance abuse. Incorrect interpretation of laboratory results can multiply negative impacts on clinical outcomes and may lead to patient harm or death. This report introduces the complex nature involved in understanding and interpreting urine drug testing (UDT) results in pain patients who are prescribed opioid medications. Laboratory testing examples of UDT results are provided to illustrate the sometimes discordant nature of UDT interpretation. This case study describes one method of approaching cases where laboratory result interpretation in pain clinic patients is essential for medical treatment and management. The case presented in this manuscript illustrates a reconciliation of an opiate positive immunoassay result in a patient who was prescribed only OxyContin and Wellbutrin after traumatic amputations.

  8. General pharmacological properties of a new non-opiate antitussive: zipeprol (3024 CERM). II. Actions on the cardiovascular system, intestinal transit and central nervous system.

    Science.gov (United States)

    Cosnier, D; Hache, J; Labrid, C; Rispat, G

    1976-01-01

    The effects of 1-(2-methoxy-2-phenyl)-ethyl-4-(2-hydroxy-3-methoxy-3-phenyl)-propyl-piperazine-dihydrochloride (zipeprol, 3024 CERM, Respilene), a new nonopiate antitussive agent, have been studied on the cardiovascular system, intestinal function and the central nervous system. Most of these studies were performed comparatively with reference antitussives, particularly codeine, whose activites in these fields are the basis of its undesirable side effects. In the dog, zipeprol showed no hypotensive or cardiac-depressant activity. It did not alter pulmonary arterial pressure. An important antiarrhythmic action was apparent in studies on rhythm disturbances induced by ouabain and coronary ligation. Intestinal function, measured by the recording of peristaltic movements in the dog and the speed of intestinal transit in the rat, was not modified by the product. Zipeprol showed no characteristic action on the central nervous system. Analgesic activity was seen only at doses just below toxic levels. Finally in the rat and the mouse, no evidence of physical dependence was seen after prolonged treatment. This together with the absence of chemical similarity to the morphinics, leads to exclude the possibility of zipeprol treatment leading to addiction. The results of these studies allow zipeprol to be clearly distinguished from the opiate antitussives.

  9. Activation of mu opioid receptor inhibits the excitatory glutamatergic transmission in the anterior cingulate cortex of the rats with peripheral inflammation.

    Science.gov (United States)

    Zheng, Weihong

    2010-02-25

    Emerging evidence recently indicates that the anterior cingulate cortex is critically involved in the central processing and modulation of noxious stimulus, although the neuroadaptation in the anterior cingulate cortex has not been well documented in the conditions of chronic pain. Meanwhile, the cellular mechanism underlying opiate analgesia in the anterior cingulate cortex remains unclear. To address these issues, the present study was undertaken to explore the adaptation of excitatory glutamatergic transmission and mu opioid receptor-mediated modulation of glutamatergic transmission in the anterior cingulate cortex slices from the complete Freund's adjuvant (CFA)-inflamed rats. The results demonstrated that glutamatergic paired-pulse facilitation was decreased in the anterior cingulate cortex neurons from the CFA-inflamed rats, indicating an enhanced presynaptic glutamate release. In addition, activation of mu opioid receptor significantly inhibited the glutamatergic excitatory postsynaptic currents (EPSCs) in the anterior cingulate cortex neurons, which was attained through the suppression of presynaptic glutamate release. Taken together, these findings provided the evidence for the functional adaptation of central glutamatergic transmission induced by peripheral inflammation, and elucidated the cellular mechanism underlying opiate analgesia in the anterior cingulate cortex.

  10. (99m)Tc-Cyclopentadienyl Tricarbonyl Chelate-Labeled Compounds as Selective Sigma-2 Receptor Ligands for Tumor Imaging.

    Science.gov (United States)

    Li, Dan; Chen, Yuanyuan; Wang, Xia; Deuther-Conrad, Winnie; Chen, Xin; Jia, Bing; Dong, Chengyan; Steinbach, Jörg; Brust, Peter; Liu, Boli; Jia, Hongmei

    2016-02-11

    We have designed and synthesized a series of cyclopentadienyl tricarbonyl rhenium complexes containing a 5,6-dimethoxyisoindoline or a 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline pharmacophore as σ2 receptor ligands. Rhenium compound 20a possessed low nanomolar σ2 receptor affinity (K(i) = 2.97 nM) and moderate subtype selectivity (10-fold). Moreover, it showed high selectivity toward vesicular acetylcholine transporter (2374-fold), dopamine D2L receptor, NMDA receptor, opiate receptor, dopamine transporter, norepinephrine transporter, and serotonin transporter. Its corresponding radiotracer [(99m)Tc]20b showed high uptake in a time- and dose-dependent manner in DU145 prostate cells and C6 glioma cells. In addition, this tracer exhibited high tumor uptake (5.92% ID/g at 240 min) and high tumor/blood and tumor/muscle ratios (21 and 16 at 240 min, respectively) as well as specific binding to σ receptors in nude mice bearing C6 glioma xenografts. Small animal SPECT/CT imaging of [(99m)Tc]20b in the C6 glioma xenograft model demonstrated a clear visualization of the tumor at 180 min after injection.

  11. [Opioid μ receptors mediate the stress-induced spatial reference memory impairment].

    Science.gov (United States)

    Cao, Lan-Qin; Wen, Jie; Liu, Zhi-Qiang

    2015-04-25

    Learning/memory impairment is one of the most serious problems induced by stress, and the underlying mechanisms remain unclear. Opiates and opioid receptors are implicated in multiple physiological functions including learning and memory. However, there is no clear evidence whether the endogenous opioid system is involved in the formation of the stress-induced spatial reference memory impairment. The aim of the present study was to evaluate the role of μ opioid receptor in the stress-induced spatial reference memory impairment by means of Morris water maze (MWM) test in a mouse elevated platform stress model. The mice were trained in the MWM for four trials a session for 4 consecutive days after receiving the elevated platform stress, and intracerebroventricular injection of μ opioid receptor agonist DAMGO, antagonist CTAP or saline. Retention of the spatial training was assessed 24 h after the last training session with a 60-s free-swim probe trial using a new starting position. The results showed that intracerebroventricular injection of μ opioid receptor agonist DAMGO but not antagonist CTAP before MWM training impaired the memory retrieval of mice. Elevated platform stress before MWM training also impaired memory retrieval, which could be reversed by pre-injection of CTAP, and aggravated by DAMGO. These results suggest that endogenous opioid system may play a crucial role in the formation of the stress-induced memory impairment.

  12. Antagonistas de los receptores glutamatérgicos NMDA en el tratamiento del dolor crónico NMDA glutamatergic receptor antagonists for the management of chronic pain

    Directory of Open Access Journals (Sweden)

    F. Neira

    2004-05-01

    (ketamine, memantine, amantadine, dextromethorphan, methadone is analyzed. Their potential indications include: cancer-related neuropathic pain; postherpetic neuralgia, chronic traumatism; amputation; spine injury; centrally-originated pain secondary to cerebrovascular accident, phantom limb pain; restless legs syndrome, orofacial chronic pain; fibromyalgia and surgery, among others. The effectiveness of ketamine when orally or parenterally administered has been studied in central dysesthesic pain, neuropathic pain in the traumatic cauda equina syndrome, alodynia and hyperalgesia. Dextromethorphan is a non-opiate antitussive and a non-competitive blocker of NMDA receptors. One of its indications is the management of diabetic neuropathy. Methadone binds mainly to opiate receptors mu, but it is also a non-competitive antagonist of NMDA receptors. The use of methadone improves the management of pain since it reduces the development of tolerance to opiates. Memantine is a non-competitive antagonist of NMDA receptors. It reduces the intracortical activation and increases the intracortical inhibition. Experimentally, it has shown antinociceptive effects during the phase secondary to the inflammation induced by the formaline test. It reduces the thermal and mechanical hyperalgesia. NMDA receptor antagonists open new perspectives for the management of neuropathic pain. These drugs are frequently combined with other analgesics, generally acting as coadjuvants. The disparate results obtained with different antagonists used for the same indication confirm the complexity of their mechanism of action, which is not limited to antagonism of NMDA receptors, but it goes much more beyond that.

  13. Effect of electromagnetic field on cyclic adenosine monophosphate (cAMP) in a human mu-opioid receptor cell model.

    Science.gov (United States)

    Ross, Christina L; Teli, Thaleia; Harrison, Benjamin S

    2016-01-01

    During the cell communication process, endogenous and exogenous signaling affect normal as well as pathological developmental conditions. Exogenous influences such as extra-low-frequency electromagnetic field (EMF) have been shown to effect pain and inflammation by modulating G-protein receptors, down-regulating cyclooxygenase-2 activity, and affecting the calcium/calmodulin/nitric oxide pathway. Investigators have reported changes in opioid receptors and second messengers, such as cyclic adenosine monophosphate (cAMP), in opiate tolerance and dependence by showing how repeated exposure to morphine decreases adenylate cyclase activity causing cAMP to return to control levels in the tolerant state, and increase above control levels during withdrawal. Resonance responses to biological systems using exogenous EMF signals suggest that frequency response characteristics of the target can determine the EMF biological response. In our past research we found significant down regulation of inflammatory markers tumor necrosis factor alpha (TNF-α) and nuclear factor kappa B (NFκB) using 5 Hz EMF frequency. In this study cAMP was stimulated in Chinese Hamster Ovary (CHO) cells transfected with human mu-opioid receptors, then exposed to 5 Hz EMF, and outcomes were compared with morphine treatment. Results showed a 23% greater inhibition of cAMP-treating cells with EMF than with morphine. In order to test our results for frequency specific effects, we ran identical experiments using 13 Hz EMF, which produced results similar to controls. This study suggests the use of EMF as a complementary or alternative treatment to morphine that could both reduce pain and enhance patient quality of life without the side-effects of opiates.

  14. Reliability and Development of Opiate Addiction Severity Inventory%阿片依赖程度评定量表的编制与信度测试

    Institute of Scientific and Technical Information of China (English)

    连智; 刘志民

    2004-01-01

    目的:编制阿片依赖程度评定量表,并对量表进行信度检验.方法:参考相关文献自行设计"12项阿片依赖程度量表"(12 Items Opiate Addiction SeverityInventory,OASI-12),对北京市公安局强制戒毒所收治的360例海洛因依赖者进行结构性访谈.其中88例首次评估后2周重测.依据访谈获得的数据采用同质性信度和重测信度对量表进行信度评价.结果:同质性信度:各因子及量表总的Cronbach's α系数在0.4128~0.8224之间.各症状项目分与总分的相关系数在0.473~0.670之间,P值均为0.000.重测信度:12个条目的重测相关系数在0.581~0.900之间,P值均为0.000.各因子的重测相关系数在0.793~0.858之间,P值均为0.000.量表总分的重测相关系数为0.872,P值均为0.000.结论:该量表具有较好的同质性信度和重测信度.

  15. A validated hybrid quadrupole linear ion-trap LC-MS method for the analysis of morphine and morphine glucuronides applied to opiate deaths.

    Science.gov (United States)

    Taylor, Kerry; Elliott, Simon

    2009-05-30

    A hybrid quadrupole linear ion-trap mass spectrometer using an electrospray ionisation ion source coupled to a HPLC system has been used to develop a method which can accurately measure morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) in plasma, whole blood and post-mortem blood following solid-phase extraction. The method can also qualitatively detect various other opioids and related compounds including: codeine, dihydrocodeine (and metabolites), noscapine, papaverine and 6-acetylmorphine (6-AM). The method has been favourably compared to an existing laboratory method using a now discontinued radio-immunoassay technique. The advantage of measuring the glucuronides directly rather than following deconjugation by beta-glucuronidase has also been shown. Detection and quantification of compounds was achieved using multiple reaction monitoring (MRM) incorporating the use of deuterated morphine and M3G as internal standards. Precision and accuracy was determined to be less than 10% at both high and low levels for all analytes and the calibration curve was deemed linear over an acceptable range. Recovery in blood was greater than 90% and ion suppression/enhancement was shown to be less than 15%. This method was applied to over 130 post-mortem cases involving the use of heroin, prescribed morphine and codeine. The range of concentrations of morphine, M3G and M6G was large (particularly in heroin and prescribed morphine cases), reflecting the many different factors involved with therapeutic use or fatal opiate poisonings, including tolerance associated with regular use, variable dose regimens and co-administration of other drugs. Detection of other constituents of the opium poppy such as noscapine and papaverine and metabolites of diacetylmorphine in the blood (6-AM) was useful in determining the source of the morphine (i.e. illicit heroin) and the rapidity of death after administration.

  16. Examining the factor structure of the Clinical Opiate Withdrawal Scale: A secondary data analysis from the National Drug Abuse Treatment Clinical Trials Network (CTN) 0003.

    Science.gov (United States)

    Barbosa-Leiker, Celestina; McPherson, Sterling; Mamey, Mary Rose; Burns, G Leonard; Layton, Matthew E; Roll, John; Ling, Walter

    2015-07-01

    The Clinical Opiate Withdrawal Scale (COWS) is used to assess withdrawal in clinical trials and practice. The aims of this study were to examine the inter-item correlations and factor structure of the COWS in opioid-dependent men and women. This is a secondary data analysis of the National Drug Abuse Treatment Clinical Trials Network 0003, a randomized clinical trial that compared buprenorphine/naloxone tapering strategies. The trial included 11 sites in 10 US cities. Participants were opioid-dependent individuals (n=516) that had data on the COWS. The COWS at study baseline was analyzed in this study. Inter-item correlations showed weak to moderate relationships among the items. A 1-factor model did not fit the data for men (comparative fit index (CFI)=.801, root mean square error of approximation (RMSEA)=.073, weighted root mean square residual (WRMR)=1.132) or women (CFI=.694, RMSEA=.071, WRMR=.933), where resting pulse rate was not related to withdrawal for men, and yawning and gooseflesh skin was not related to withdrawal for women. A reduced model comprised of only the 8 items that were significantly related to the construct of withdrawal in both men and women, and an exploratory 2-factor model, were also assessed but not retained due to inconsistencies across gender. When traditional psychometric models are applied to the COWS, it appears that the scale may not relate to a single underlying construct of withdrawal. Further research testing the hypothesized factor structure in other opioid-dependent samples is needed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Direct Injection LC-MS-MS Analysis of Opiates, Methamphetamine, Buprenorphine, Methadone and Their Metabolites in Oral Fluid from Substitution Therapy Patients.

    Science.gov (United States)

    Liu, Hsiu-Chuan; Lee, Hsi-Tzu; Hsu, Ya-Ching; Huang, Mei-Han; Liu, Ray H; Chen, Tai-Jui; Lin, Dong-Liang

    2015-01-01

    A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed, validated and applied to simultaneous analysis of oral fluid samples for the following 10 analytes: methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, norbuprenorphine, morphine, codeine, 6-acetylmorphine, 6-acetylcodeine, amphetamine, and methamphetamine. The oral fluid sample was briefly centrifuged and the supernatant was directly injected into the LC-MS-MS system operated under reverse-phase chromatography and electrospray ionization (ESI). Deuterated analogs of the analytes were adopted as the internal standards and found to be effective (except for buprenorphine) to compensate for potential matrix effects. Each analytical run took 0.99) established for buprenorphine and the other nine analytes were 5-100 and 1-100 ng/mL. Intra- and interday precision (% CV) ranges for the 10 analytes were 0.87-12.2% and 1.27-12.8%, while the corresponding accuracy (%) ranges were 91.8-113% and 91.9-111%. Limits of detection and quantitation established for these 10 analytes were in the ranges of 0.1-1.0 and 0.25-1.0 ng/mL (5 ng/mL for buprenorphine). The method was successfully applied to the analysis of 62 oral fluid specimens collected from patients participating in methadone and buprenorphine substitution therapy programs. Analytical results of methadone and buprenorphine were compared with data derived from GC-MS analysis and found to be compatible. Overall, the direct injection LC-MS-MS method performed well, permitting rapid analysis of oral fluid samples for simultaneous quantification of methadone, buprenorphine, opiate and amphetamine drug categories without extensive sample preparation steps.

  18. Examining the factor structure of the Clinical Opiate Withdrawal Scale: A secondary data analysis from the National Drug Abuse Treatment Clinical Trials Network (CTN) 0003

    Science.gov (United States)

    Barbosa-Leiker, Celestina; McPherson, Sterling; Mamey, Mary Rose; Burns, G. Leonard; Layton, Matthew E.; Roll, John; Ling, Walter

    2015-01-01

    Background The Clinical Opiate Withdrawal Scale (COWS) is used to assess withdrawal in clinical trials and practice. The aims of this study were to examine the inter-item correlations and factor structure of the COWS in opioid-dependent men and women. Methods This is a secondary data analysis of the National Drug Abuse Treatment Clinical Trials Network 0003, a randomized clinical trial that compared buprenorphine/naloxone tapering strategies. The trial included 11 sites in 10 US cities. Participants were opioid-dependent individuals (n=516) that had data on the COWS. The COWS at study baseline was analyzed in this study. Results Inter-item correlations showed weak to moderate relationships among the items. A 1-factor model did not fit the data for men (comparative fit index (CFI)=.801, root mean square error of approximation (RMSEA)=.073, weighted root mean square residual (WRMR)=1.132) or women (CFI=.694, RMSEA=.071, WRMR=.933), where resting pulse rate was not related to withdrawal for men, and yawning and gooseflesh skin was not related to withdrawal for women. A reduced model comprised of only the 8 items that were significantly related to the construct of withdrawal in both men and women, and an exploratory 2-factor model, were also assessed but not retained due to inconsistencies across gender. Conclusions When traditional psychometric models are applied to the COWS, it appears that the scale may not relate to a single underlying construct of withdrawal. Further research testing the hypothesized factor structure in other opioid-dependent samples is needed. PMID:25908321

  19. The newer Opioid Agonist Treatment with lower substitutive opiate doses is associated with better toxicology outcome than the older Harm Reduction Treatment.

    Science.gov (United States)

    Bizzarri, Jacopo V; Casetti, Valentina; Sanna, Livia; Maremmani, Angelo Giovanni Icro; Rovai, Luca; Bacciardi, Silvia; Piacentino, Daria; Conca, Andreas; Maremmani, Icro

    2016-01-01

    Charge-free heroin use disorder treatment in Italy follows two main approaches, i.e., harm reduction treatment (HRT) strategy in community low-threshold facilities for drug addiction and opioid agonist treatment (OAT) in high-threshold facilities for opioid addiction, focusing on pharmacological maintenance according to the Dole and Nyswander strategy. We aimed to compare the impact of HRT and OAT on patient outcome, as assessed through negativity for drugs on about 1-year urinalyses. We examined retrospectively the urinalyses of HRT and OAT patients for which at least four randomly sampled urinalyses per month were available for about 1 year, during which patients were undergoing methadone or buprenorphine maintenance; urinalyses focused on heroin, cocaine, cannabinoids, and their metabolites. Included were 189 HRT and 58 OAT patients. The latter were observed for a significantly longer period. There was a higher proportion of heroin- and cocaine-clean urinalyses in OAT patients, with cocaine-clean urinalyses discriminating best between the two groups. OAT patients were older, with longer dependence duration, more severe addiction history, and received lower methadone doses. Buprenorphine maintenance was more often associated with heroin-clean urinalyses. The higher the methadone doses, the lower were the percentage of heroin-clean urinalyses in HRT patients (negative correlation). The OAT approach was related to higher recovery and polyabuse abstinence rates compared to the HRT approach, despite greater severity of substance use, psychiatric and physical comorbidities. Our results are consistent with the possibility to use lower maintenance opiate doses (after induction and stabilization in methadone treatment according to Dole and Nyswander methodology) in treating heroin addiction. This seemed to be impossible adopting the currently accepted HRT model.

  20. Involvement of mammalian RF-amide peptides and their receptors in the modulation of nociception in rodents

    Directory of Open Access Journals (Sweden)

    Safia eAyachi

    2014-10-01

    Full Text Available Mammalian RF-amide peptides, which all share a conserved carboxyl-terminal Arg-Phe-NH2 sequence, constitute a family of five groups of neuropeptides that are encoded by five different genes. They act through five G protein-coupled receptors and each group of peptide binds to and activates mostly one receptor: RF-amide related peptide (RFRP group binds to NPFFR1, neuropeptide FF (NPFF group to NPFFR2, pyroglutamylated RF-amide peptide (QRFP group to QRFPR, prolactin releasing peptide (PrRP group to PrRPR, and kisspeptin group to Kiss1R. These peptides and their receptors have been involved in the modulation of several functions including reproduction, feeding and cardiovascular regulation. Data from the literature now provide emerging evidence that all RF-amide peptides and their receptors are also involved in the modulation of nociception. This review will present the current knowledge on the involvement in rodents of the different mammalian RF-amide peptides and their receptors in the modulation of nociception in basal and chronic pain conditions as well as their modulatory effects on the analgesic effects of opiates.

  1. The androgen receptor and estrogen receptor

    NARCIS (Netherlands)

    Oosterkamp, H.M.; Bernards, R.A.

    2002-01-01

    The androgen receptor (AR) and the estrogen receptors (ER) are members of the nuclear receptor (NR) family. These NRs are distinguished from the other transcription factors by their ability to control gene expression upon ligand binding (steroids, retinoids, thyroid hormone, vitamin D, fatty acids,

  2. Interaction of trimebutine and Jo-1196 (fedotozine) with opioid receptors in the canine ileum

    Energy Technology Data Exchange (ETDEWEB)

    Allescher, H.D.; Ahmad, S.; Classen, M.; Daniel, E.E. (Technical Univ., Munich, (West Germany))

    1991-05-01

    Receptor binding of the opioid receptor antagonist, ({sup 3}H)diprenorphine, which has a similar affinity to the various opioid receptor subtypes, was characterized in subcellular fractions derived from either longitudinal or circular smooth muscle of the canine small intestine with their plexuses (myenteric plexus and deep muscular plexus, respectively) attached. The distribution of opioid binding activity showed a good correlation in the different fractions with the binding of the neuronal marker ({sup 3}H)saxitoxin but no correlation to the smooth muscle plasma membrane marker 5'-nucleotidase. The saturation data (Kd = 0.12 +/- 0.04 nM and maximum binding = 400 +/- 20 fmol/mg) and the data from kinetic experiments (Kd = 0.08 nmol) in the myenteric plexus were in good agreement with results obtained previously from the circular muscle/deep muscular plexus preparation. Competition experiments using selective drugs for mu (morphiceptin-analog (N-MePhe3-D-Pro4)-morphiceptin), delta (D-Pen2,5-enkephalin) and kappa (dynorphin 1-13, U50488-H) ligands showed the existence of all three receptor subtypes. The existence of kappa receptors was confirmed in saturation experiments using ({sup 3}H) ethylketocycloazocine as labeled ligand. Two putative opioid agonists, with effects on gastrointestinal motility, trimebutine and JO-1196 (fedotozin), were also examined. Trimebutine (Ki = 0.18 microM), Des-Met-trimebutine (Ki = 0.72 microM) and Jo-1196 (Ki = 0.19 microM) displaced specific opiate binding. The relative affinity for the opioid receptor subtypes was mu = 0.44, delta = 0.30 and kappa = 0.26 for trimebutine and mu = 0.25, delta = 0.22 and kappa = 0.52 for Jo-1196.

  3. Hippocampal GluA1-containing AMPA receptors mediate context-dependent sensitization to morphine.

    Science.gov (United States)

    Xia, Yan; Portugal, George S; Fakira, Amanda K; Melyan, Zara; Neve, Rachael; Lee, H Thomas; Russo, Scott J; Liu, Jie; Morón, Jose A

    2011-11-09

    Glutamatergic systems, including AMPA receptors (AMPARs), are involved in opiate-induced neuronal and behavioral plasticity, although the mechanisms underlying these effects are not fully understood. In the present study, we investigated the effects of repeated morphine administration on AMPAR expression, synaptic plasticity, and context-dependent behavioral sensitization to morphine. We found that morphine treatment produced changes of synaptic AMPAR expression in the hippocampus, a brain area that is critically involved in learning and memory. These changes could be observed 1 week after the treatment, but only when mice developed context-dependent behavioral sensitization to morphine in which morphine treatment was associated with drug administration environment. Context-dependent behavioral sensitization to morphine was also associated with increased basal synaptic transmission and disrupted hippocampal long-term potentiation (LTP), whereas these effects were less robust when morphine administration was not paired with the drug administration environment. Interestingly, some effects may be related to the prior history of morphine exposure in the drug-associated environment, since alterations of AMPAR expression, basal synaptic transmission, and LTP were observed in mice that received a saline challenge 1 week after discontinuation of morphine treatment. Furthermore, we demonstrated that phosphorylation of GluA1 AMPAR subunit plays a critical role in the acquisition and expression of context-dependent behavioral sensitization, as this behavior is blocked by a viral vector that disrupts GluA1 phosphorylation. These data provide evidence that glutamatergic signaling in the hippocampus plays an important role in context-dependent sensitization to morphine and supports further investigation of glutamate-based strategies for treating opiate addiction.

  4. Integration of GC/EI-MS and GC/NCI-MS for simultaneous quantitative determination of opiates, amphetamines, MDMA, ketamine, and metabolites in human hair.

    Science.gov (United States)

    Wu, Ya-Hsueh; Lin, Keh-Liang; Chen, Su-Chin; Chang, Yan-Zin

    2008-07-15

    In this paper, the possibility of using a multiple ionization mode approach of GC/MS was developed for the simultaneous hair testing of common drugs of abuse in Asia, including amphetamines (amphetamine, AP; methamphetamine, MA; methylenedioxy amphetamine, MDA; methylenedioxy methamphetamine, MDMA; methylenedioxy ethylamphetamine, MDEA), ketamine (ketamine, K; norketamine, NK), and opiates (morphine, MOR; codeine, COD; 6-acetylmorphine, 6-AM). This strategy integrated the characteristics of gas chromatography-mass spectrometry (GC-MS) using electron impact ionization (EI) and negative chemical ionization (NCI). Hair samples (25 mg) were washed, cut, and incubated overnight at 25 degrees C in methanol-trifluoroacetic acid (methanol-TFA). The samples were extracted by solid phase extraction (SPE) procedure, derivatized using heptafluorobutyric acid anhydride (HFBA) at 70 degrees C for 30 min, and the derivatives analyzed by GC-MS with EI and NCI. The limit of detection (LOD) with GC/EI-MS analysis obtained were 0.03 ng/mg for AP, MA, MDA, MDMA, and MDEA; 0.05 ng/mg for K, NK, MOR, and COD; and 0.08 ng/mg for 6-AM. The LOD of GC/NCI-MS analysis was much lower than GC/EI-MS analysis. The LOD obtained were 30 pg/mg for AP and MDA in GC/EI-MS and 2 pg/mg in GC/NCI-MS. Therefore, the sensitivity of AP and MDA in GC/NCI-MS was improved from 15-fold compared with EI. The sensitivity of AP, MA, MDA, MDMA, MDEA, MOR, and COD was improved from 15- to 60-fold compared with EI. In addition, the sensitivity of 6-AM increased 8-fold through selection of m/z 197 for the quantitative ion. Moreover, K and NK could dramatically improve their sensitivity at 200- and 2000-fold. The integration of GC/EI-MS and GC/NCI-MS can obtain the high sensitivity and complementary results of drugs of abuse in hair. Six hair samples from known drug abusers were examined by this new strategy. These results show that integrating the characteristics of GC/EI-MS and GC/NCI-MS were not only enhancement of

  5. GLP-1 Receptor Agonists

    Science.gov (United States)

    ... in Balance › GLP-1 Receptor Agonists Fact Sheet GLP-1 Receptor Agonists May, 2012 Download PDFs English Espanol Editors Silvio ... are too high or too low. What are GLP-1 receptor agonist medicines? GLP-1 receptor agonist medicines, also called ...

  6. 液相色谱-串联质谱法测定头发中11种阿片类生物碱%Simultaneous determination of 11 opiates in hair by liquid chromatography-tandem mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    孙英英; 向平; 沈敏

    2011-01-01

    The paper reports the establishment of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) for simultaneous analysis of 11 opiates in hair samples, and the study of presence of opiates in the hair of active heroin addicts. About 20 mg of decontaminated and pulverized hair sample was hydrolyzed with buffer solution for 30 min, in the presence of morphine-d3 and acetylmorphine-d6 used as internal standards, and then extracted with the mixture of dichlormethane and isopropanol, separated by the Allure PFP propyl column with a mobile phase consisting of acetonitrile and 20 mmol·L-1 ammonium acetate buffer, and then analyzed by LC-MS/MS. Multiple reaction monitoring (MRM) mode was used to analyze 11 opiates. Eleven opiates showed a fairly good linearity over the corresponding range (r > 0.996 0). The detection limits were less than 0.05 ng·mg-1. The recoveries were between 47.2% and 110%, and the deviations of intra- and inter-day precision were less than 14%. Heroin, acetylmorphine, morphine, codeine, acetylcodeine and hydrocodone were detected in hair samples of 21 herion addicts. The developed method shows high sensitivity and selectivity, and is suitable for the simultaneous analysis of 1 lopiates in hair samples and identify legal and illegal use of opiates.%建立头发中海洛因、吗啡、单乙酰吗啡等11种阿片类生物碱的液相色谱-串联质谱测定方法,并考察海洛因滥用者头发中阿片类组分的存在情况.头发经冷冻研磨后加入硼酸缓冲液超声30 min,用氯仿-异丙醇(9∶1)提取.用Allure PFP丙基柱,以乙腈-乙酸铵(0.1%甲酸)梯度洗脱分离,采用二级质谱多反应监测模式(MRM)检测11种阿片类生物碱.头发中海洛因、吗啡、单乙酰吗啡等11种阿片类生物碱在对应质量浓度范围内线性良好(r> 0.996 0);检测限(LOD)均小于0.05 ng·mg-1;回收率范围为47.2%~110%;日内精密度和日间精密度均小于14%.21例海洛因滥用者头发中

  7. [{sup 11}C]-MeJDTic: a novel radioligand for {kappa}-opioid receptor positron emission tomography imaging

    Energy Technology Data Exchange (ETDEWEB)

    Poisnel, Geraldine; Oueslati, Farhana; Dhilly, Martine; Delamare, Jerome [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France); Perrio, Cecile [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail: perrio@cyceron.fr; Debruyne, Daniele [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)], E-mail: debruyne@cyceron.fr; Barre, Louisa [Groupe de Developpements Methodologiques en Tomographie par Emission de Positons, DSV/DRM UMR CEA 2E, Universite de Caen-Basse Normandie, Centre Cyceron, 14074 Caen Cedex (France)

    2008-07-15

    Introduction: Radiopharmaceuticals that can bind selectively the {kappa}-opioid receptor may present opportunities for staging clinical brain disorders and evaluating the efficiency of new therapies related to stroke, neurodegenerative diseases or opiate addiction. The N-methylated derivative of JDTic (named MeJDTic), which has been recently described as a potent and selective antagonist of {kappa}-opioid receptor in vitro, was labeled with carbon-11 and evaluated for in vivo imaging the {kappa}-opioid receptor in mice. Methods: [{sup 11}C]-MeJDTic was prepared by methylation of JDTic with [{sup 11}C]-methyl triflate. The binding of [{sup 11}C]-MeJDTic to {kappa}-opioid receptor was investigated ex vivo by biodistribution and competition studies using nonfasted male CD1 mice. Results: [{sup 11}C]-MeJDTic exhibited a high and rapid distribution in peripheral organs. The uptake was maximal in lung where the {kappa} receptor is largely expressed. [{sup 11}C]-MeJDTic rapidly crossed the blood-brain barrier and accumulated in the brain regions of interest (hypothalamus). The parent ligand remained the major radioactive compound in brain during the experiment. Chase studies with U50,488 (a {kappa} referring agonist), morphine (a {mu} agonist) and naltrindole (a {delta} antagonist) demonstrated that this uptake was the result of specific binding to the {kappa}-opioid receptor. Conclusion: These findings suggested that [{sup 11}C]-MeJDTic appeared to be a promising selective 'lead' radioligand for {kappa}-opioid receptor PET imaging.

  8. The metabotropic glutamate 5 receptor modulates extinction and reinstatement of methamphetamine-seeking in mice.

    Directory of Open Access Journals (Sweden)

    Rose Chesworth

    Full Text Available Methamphetamine (METH is a highly addictive psychostimulant with no therapeutics registered to assist addicts in discontinuing use. Glutamatergic dysfunction has been implicated in the development and maintenance of addiction. We sought to assess the involvement of the metabotropic glutamate 5 receptor (mGlu5 in behaviours relevant to METH addiction because this receptor has been implicated in the actions of other drugs of abuse, including alcohol, cocaine and opiates. mGlu5 knockout (KO mice were tested in intravenous self-administration, conditioned place preference and locomotor sensitization. Self-administration of sucrose was used to assess the response of KO mice to a natural reward. Acquisition and maintenance of self-administration, as well as the motivation to self-administer METH was intact in mGlu5 KO mice. Importantly, mGlu5 KO mice required more extinction sessions to extinguish the operant response for METH, and exhibited an enhanced propensity to reinstate operant responding following exposure to drug-associated cues. This phenotype was not present when KO mice were tested in an equivalent paradigm assessing operant responding for sucrose. Development of conditioned place preference and locomotor sensitization were intact in KO mice; however, conditioned hyperactivity to the context previously paired with drug was elevated in KO mice. These data demonstrate a role for mGlu5 in the extinction and reinstatement of METH-seeking, and suggests a role for mGlu5 in regulating contextual salience.

  9. Inhibition of Activity of GABA Transporter GAT1 by δ-Opioid Receptor

    Directory of Open Access Journals (Sweden)

    Lu Pu

    2012-01-01

    Full Text Available Analgesia is a well-documented effect of acupuncture. A critical role in pain sensation plays the nervous system, including the GABAergic system and opioid receptor (OR activation. Here we investigated regulation of GABA transporter GAT1 by δOR in rats and in Xenopus oocytes. Synaptosomes of brain from rats chronically exposed to opiates exhibited reduced GABA uptake, indicating that GABA transport might be regulated by opioid receptors. For further investigation we have expressed GAT1 of mouse brain together with mouse δOR and μOR in Xenopus oocytes. The function of GAT1 was analyzed in terms of Na+-dependent [3H]GABA uptake as well as GAT1-mediated currents. Coexpression of δOR led to reduced number of fully functional GAT1 transporters, reduced substrate translocation, and GAT1-mediated current. Activation of δOR further reduced the rate of GABA uptake as well as GAT1-mediated current. Coexpression of μOR, as well as μOR activation, affected neither the number of transporters, nor rate of GABA uptake, nor GAT1-mediated current. Inhibition of GAT1-mediated current by activation of δOR was confirmed in whole-cell patch-clamp experiments on rat brain slices of periaqueductal gray. We conclude that inhibition of GAT1 function will strengthen the inhibitory action of the GABAergic system and hence may contribute to acupuncture-induced analgesia.

  10. Toward a structure-based model of salvinorin A recognition of the kappa-opioid receptor.

    Science.gov (United States)

    Kane, Brian E; McCurdy, Christopher R; Ferguson, David M

    2008-03-27

    The structural basis to salvinorin A recognition of the kappa-opioid receptor is evaluated using a combination of site-directed mutagenesis and molecular-modeling techniques. The results show that salvinorin A recognizes a collection of residues in transmembrane II and VII, including Q115, Y119, Y313, I316, and Y320. The mutation of one hydrophobic residue in particular, I316, was found to completely abolish salvinorin A binding. As expected, none of the residues in transmembrane III or VI commonly associated with opiate recognition (such as D138 or E297) appear to be required for ligand binding. On the basis of the results presented here and elsewhere, a binding site model is proposed that aligns salvinorin A vertically within a pocket spanning transmembrane II and VII, with the 2' substituent directed toward the extracellular domains. The model explains the role that hydrophobic contacts play in binding this lipophilic ligand and gives insight into the structural basis to the mu-opioid receptor selectivity of 2'-benzoyl salvinorin (herkinorin).

  11. The metabotropic glutamate 5 receptor modulates extinction and reinstatement of methamphetamine-seeking in mice.

    Science.gov (United States)

    Chesworth, Rose; Brown, Robyn M; Kim, Jee Hyun; Lawrence, Andrew J

    2013-01-01

    Methamphetamine (METH) is a highly addictive psychostimulant with no therapeutics registered to assist addicts in discontinuing use. Glutamatergic dysfunction has been implicated in the development and maintenance of addiction. We sought to assess the involvement of the metabotropic glutamate 5 receptor (mGlu5) in behaviours relevant to METH addiction because this receptor has been implicated in the actions of other drugs of abuse, including alcohol, cocaine and opiates. mGlu5 knockout (KO) mice were tested in intravenous self-administration, conditioned place preference and locomotor sensitization. Self-administration of sucrose was used to assess the response of KO mice to a natural reward. Acquisition and maintenance of self-administration, as well as the motivation to self-administer METH was intact in mGlu5 KO mice. Importantly, mGlu5 KO mice required more extinction sessions to extinguish the operant response for METH, and exhibited an enhanced propensity to reinstate operant responding following exposure to drug-associated cues. This phenotype was not present when KO mice were tested in an equivalent paradigm assessing operant responding for sucrose. Development of conditioned place preference and locomotor sensitization were intact in KO mice; however, conditioned hyperactivity to the context previously paired with drug was elevated in KO mice. These data demonstrate a role for mGlu5 in the extinction and reinstatement of METH-seeking, and suggests a role for mGlu5 in regulating contextual salience.

  12. Acetylcholine receptor antibody

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood ...

  13. Androgen receptor abnormalities

    NARCIS (Netherlands)

    A.O. Brinkmann (Albert); G.G.J.M. Kuiper (George); C. Ris-Stalpers (Carolyn); H.C.J. van Rooij (Henri); G. Romalo (G.); G. Trifiro (Gianluca); E. Mulder (Eppo); L. Pinsky (L.); H.U. Schweikert (H.); J. Trapman (Jan)

    1991-01-01

    markdownabstract__Abstract__ The human androgen receptor is a member of the superfamily of steroid hormone receptors. Proper functioning of this protein is a prerequisite for normal male sexual differentiation and development. The cloning of the human androgen receptor cDNA and the elucidation of t

  14. Mammalian Sweet Taste Receptors

    National Research Council Canada - National Science Library

    Nelson, Greg; Hoon, Mark A; Chandrashekar, Jayaram; Zhang, Yifeng; Ryba, Nicholas J.P; Zuker, Charles S

    2001-01-01

    ... and information coding, and have focused on the isolation and characterization of genes encoding sweet and bitter taste receptors. The identification of taste receptors generates powerful molecular tools to investigate not only the function of taste receptor cells, but also the logic of taste coding. For example, defining the size and diversity of the re...

  15. Resting-state Functional Connectivity of Medial Prefrontal Cortex in the Active Opiates User%海洛因成瘾者前额叶内侧皮质的静息状态功能连接

    Institute of Scientific and Technical Information of China (English)

    刘海洪; 阎媛; 张会然; 郝以辉; 刘哲宁

    2013-01-01

    目的:探讨海洛因成瘾者脑默认网络静息状态功能连接的异常.方法:对正在接受美沙酮维持治疗的15例海洛因依赖者和15例健康对照进行静息状态脑功能磁共振扫描,以独立成分分析法获取每一个体的默认网络,并比较两组默认网络的功能连接差异.结果:与健康对照相比,海洛因成瘾者双侧前额叶内侧皮质、左侧颞中回和颞下回、小脑的功能连接升高.结论:前额叶内侧皮质可能是物质成瘾的关键脑区,可为成瘾的生物学诊断和靶向治疗提供线索.%Objective:To investigate the effects of active opiates use on the resting-state functional connectivity of the default network.Methods:Resting-state functional images were obtained from 15 heroin-dependent subjects on methadone maintenance therapy and 15 healthy controls matched for sex,age and education years.Individual's default network was obtained by independent component analysis,and the default network difference between the two groups was explored by two sample t test.Results:Compared with the healthy controls,active opiates user showed increased restingstate functional connectivity in bilateral medial prefrontal cortex (MPFC),left middle and inferior temporal gyrus and cerebellum.Conclusion:The MPFC may be a crucial area of substance addiction.This findings provides cues for the biological diagnosis and region-targeted therapy of addiction.

  16. 五地区阿片类物质依赖者复发特点和原因调查%SURVEY OF RELAPSE AMONG OPIATE ADDICTS IN FIVE AREAS

    Institute of Scientific and Technical Information of China (English)

    唐艳; 沈杰; 尹玲; 李煜; 刘志民; 鲍彦平; 孙桂宽; 李晓东; 李卫萍; 杨建辉; 肖早香; 秦德胜; 李军

    2011-01-01

    Objective: To investigate the general situation and related factors of relapse among opiate addicts after detoxification treatment and to explore intervention methods for relapse prevention.Methods: 1085 opiate addicts who had the experience of relapse after detoxificafion completed the" Questionnaire on Relapse for Opiate addicts" in five areas of Kuming, Yichang, Zhuhai/Zhongshan,Beijing and Shanghai.Results:Among 1085 questionnaires ,1065 were eligible questionnaires (98. 2% ).The mean age of 1065 opiate addicts was 35. 1 a ± s 7. 1 a, and their mean time of drug abuse was 10. 9 a ±s 4.4 a. The most vulnerable time for relapse was within five days (40. 2% ) when they returned to the community after detoxificafion treatment. The average value of four related factors "physiological factor,psychological factor, pharmacological factor and social factor" were 720. 8,1003. 0,1019. 5 and 1059.0,respectively,showing statistical significance (x2 = 881.8, P < 0. 001 ). The social factor was the most important factor,which induced relapse after detoxification treatment among opiate addicts in five cities. Conclusion:This survey indicates that social support and psychological intervention are effective measures for preventing opiate addicts from relapse.%目的:了解我国阿片类物质依赖人群戒毒治疗后复发的一般情况和复发的影响因素,为复发的预防干预提供依据.方法:应用自行编制的,在调查人员指导下,对昆明、宜昌、珠海/中山、北京和上海市五地区戒毒机构收治的1085名阿片类物质依赖者进行问卷调查,问卷由被调查对象集体自行匿名填写完成.结果:回收问卷1085份,可进行统计分析的有效问卷1065份(占98.2%).1065例调查对象的年龄35.1 a±s 7.1 a,滥用药物时间10.9 a±s 4.4 a;经历"强制"和"劳教"的戒毒次数为4.4±s 2.3次;出戒毒所后最易复发的时间段为"戒毒后的d1-5"(占40.2%);"躯体生理因素、心理因素、药物成瘾

  17. [Melatonin receptor agonist].

    Science.gov (United States)

    Uchiyama, Makoto

    2015-06-01

    Melatonin is a hormone secreted by the pineal gland and is involved in the regulation of human sleep-wake cycle and circadian rhythms. The melatonin MT1 and MT2 receptors located in the suprachiasmatic nucleus in the hypothalamus play a pivotal role in the sleep-wake regulation. Based on the fact that MT1 receptors are involved in human sleep onset process, melatonin receptor agonists have been developed to treat insomnia. In this article, we first reviewed functions of melatonin receptors with special reference to MT1 and MT2, and properties and clinical application of melatonin receptor agonists as hypnotics.

  18. Dopamine receptors and hypertension.

    Science.gov (United States)

    Banday, Anees Ahmad; Lokhandwala, Mustafa F

    2008-08-01

    Dopamine plays an important role in regulating renal function and blood pressure. Dopamine synthesis and dopamine receptor subtypes have been shown in the kidney. Dopamine acts via cell surface receptors coupled to G proteins; the receptors are classified via pharmacologic and molecular cloning studies into two families, D1-like and D2-like. Two D1-like receptors cloned in mammals, the D1 and D5 receptors (D1A and D1B in rodents), are linked to adenylyl cyclase stimulation. Three D2-like receptors (D2, D3, and D4) have been cloned and are linked mainly to adenylyl cyclase inhibition. Activation of D1-like receptors on the proximal tubules inhibits tubular sodium reabsorption by inhibiting Na/H-exchanger and Na/K-adenosine triphosphatase activity. Reports exist of defective renal dopamine production and/or dopamine receptor function in human primary hypertension and in genetic models of animal hypertension. In humans with essential hypertension, renal dopamine production in response to sodium loading is often impaired and may contribute to hypertension. A primary defect in D1-like receptors and an altered signaling system in proximal tubules may reduce dopamine-mediated effects on renal sodium excretion. The molecular basis for dopamine receptor dysfunction in hypertension is being investigated, and may involve an abnormal posttranslational modification of the dopamine receptor.

  19. NCBI nr-aa BLAST: CBRC-OANA-01-2124 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OANA-01-2124 gb|AAV38759.1| opiate receptor-like 1 [synthetic construct] gb|AAV38760.1| opiate... receptor-like 1 [synthetic construct] gb|AAX43081.1| opiate receptor-like 1 [synthetic construct] gb|AAX43082.1| opi...ate receptor-like 1 [synthetic construct] AAV38759.1 1e-150 69% ...

  20. NCBI nr-aa BLAST: CBRC-ETEL-01-0228 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-ETEL-01-0228 gb|AAV38759.1| opiate receptor-like 1 [synthetic construct] gb|AAV38760.1| opiate... receptor-like 1 [synthetic construct] gb|AAX43081.1| opiate receptor-like 1 [synthetic construct] gb|AAX43082.1| opi...ate receptor-like 1 [synthetic construct] AAV38759.1 1e-149 91% ...

  1. NCBI nr-aa BLAST: CBRC-HSAP-20-0024 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-HSAP-20-0024 gb|AAV38759.1| opiate receptor-like 1 [synthetic construct] gb|AAV38760.1| opiate... receptor-like 1 [synthetic construct] gb|AAX43081.1| opiate receptor-like 1 [synthetic construct] gb|AAX43082.1| opi...ate receptor-like 1 [synthetic construct] AAV38759.1 0.0 100% ...

  2. NCBI nr-aa BLAST: CBRC-TBEL-01-1256 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TBEL-01-1256 gb|AAV38759.1| opiate receptor-like 1 [synthetic construct] gb|AAV38760.1| opiate... receptor-like 1 [synthetic construct] gb|AAX43081.1| opiate receptor-like 1 [synthetic construct] gb|AAX43082.1| opi...ate receptor-like 1 [synthetic construct] AAV38759.1 4e-61 91% ...

  3. NCBI nr-aa BLAST: CBRC-PVAM-01-0526 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PVAM-01-0526 gb|AAV38759.1| opiate receptor-like 1 [synthetic construct] gb|AAV38760.1| opiate... receptor-like 1 [synthetic construct] gb|AAX43081.1| opiate receptor-like 1 [synthetic construct] gb|AAX43082.1| opi...ate receptor-like 1 [synthetic construct] AAV38759.1 1e-77 86% ...

  4. NCBI nr-aa BLAST: CBRC-PHAM-01-0451 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PHAM-01-0451 gb|AAV38759.1| opiate receptor-like 1 [synthetic construct] gb|AAV38760.1| opiate... receptor-like 1 [synthetic construct] gb|AAX43081.1| opiate receptor-like 1 [synthetic construct] gb|AAX43082.1| opi...ate receptor-like 1 [synthetic construct] AAV38759.1 0.0 98% ...

  5. NCBI nr-aa BLAST: CBRC-ACAR-01-1160 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-ACAR-01-1160 gb|AAV38759.1| opiate receptor-like 1 [synthetic construct] gb|AAV38760.1| opiate... receptor-like 1 [synthetic construct] gb|AAX43081.1| opiate receptor-like 1 [synthetic construct] gb|AAX43082.1| opi...ate receptor-like 1 [synthetic construct] AAV38759.1 1e-138 64% ...

  6. NCBI nr-aa BLAST: CBRC-CFAM-24-0010 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CFAM-24-0010 gb|AAV38759.1| opiate receptor-like 1 [synthetic construct] gb|AAV38760.1| opiate... receptor-like 1 [synthetic construct] gb|AAX43081.1| opiate receptor-like 1 [synthetic construct] gb|AAX43082.1| opi...ate receptor-like 1 [synthetic construct] AAV38759.1 0.0 96% ...

  7. NCBI nr-aa BLAST: CBRC-MEUG-01-1362 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MEUG-01-1362 gb|AAV38759.1| opiate receptor-like 1 [synthetic construct] gb|AAV38760.1| opiate... receptor-like 1 [synthetic construct] gb|AAX43081.1| opiate receptor-like 1 [synthetic construct] gb|AAX43082.1| opi...ate receptor-like 1 [synthetic construct] AAV38759.1 1e-106 80% ...

  8. NCBI nr-aa BLAST: CBRC-TGUT-23-0006 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TGUT-23-0006 gb|AAV38759.1| opiate receptor-like 1 [synthetic construct] gb|AAV38760.1| opiate... receptor-like 1 [synthetic construct] gb|AAX43081.1| opiate receptor-like 1 [synthetic construct] gb|AAX43082.1| opi...ate receptor-like 1 [synthetic construct] AAV38759.1 1e-141 66% ...

  9. NCBI nr-aa BLAST: CBRC-GGAL-20-0003 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GGAL-20-0003 gb|AAV38759.1| opiate receptor-like 1 [synthetic construct] gb|AAV38760.1| opiate... receptor-like 1 [synthetic construct] gb|AAX43081.1| opiate receptor-like 1 [synthetic construct] gb|AAX43082.1| opi...ate receptor-like 1 [synthetic construct] AAV38759.1 1e-141 66% ...

  10. NCBI nr-aa BLAST: CBRC-MMUR-01-0596 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MMUR-01-0596 gb|AAV38759.1| opiate receptor-like 1 [synthetic construct] gb|AAV38760.1| opiate... receptor-like 1 [synthetic construct] gb|AAX43081.1| opiate receptor-like 1 [synthetic construct] gb|AAX43082.1| opi...ate receptor-like 1 [synthetic construct] AAV38759.1 0.0 96% ...

  11. NCBI nr-aa BLAST: CBRC-PABE-21-0028 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PABE-21-0028 gb|AAV38759.1| opiate receptor-like 1 [synthetic construct] gb|AAV38760.1| opiate... receptor-like 1 [synthetic construct] gb|AAX43081.1| opiate receptor-like 1 [synthetic construct] gb|AAX43082.1| opi...ate receptor-like 1 [synthetic construct] AAV38759.1 0.0 98% ...

  12. NCBI nr-aa BLAST: CBRC-MLUC-01-0678 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MLUC-01-0678 gb|AAV38759.1| opiate receptor-like 1 [synthetic construct] gb|AAV38760.1| opiate... receptor-like 1 [synthetic construct] gb|AAX43081.1| opiate receptor-like 1 [synthetic construct] gb|AAX43082.1| opi...ate receptor-like 1 [synthetic construct] AAV38759.1 0.0 91% ...

  13. NCBI nr-aa BLAST: CBRC-CJAC-01-0417 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CJAC-01-0417 gb|AAV38759.1| opiate receptor-like 1 [synthetic construct] gb|AAV38760.1| opiate... receptor-like 1 [synthetic construct] gb|AAX43081.1| opiate receptor-like 1 [synthetic construct] gb|AAX43082.1| opi...ate receptor-like 1 [synthetic construct] AAV38759.1 1e-121 99% ...

  14. NCBI nr-aa BLAST: CBRC-DNOV-01-1501 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-1501 gb|AAV38759.1| opiate receptor-like 1 [synthetic construct] gb|AAV38760.1| opiate... receptor-like 1 [synthetic construct] gb|AAX43081.1| opiate receptor-like 1 [synthetic construct] gb|AAX43082.1| opi...ate receptor-like 1 [synthetic construct] AAV38759.1 1e-152 92% ...

  15. NCBI nr-aa BLAST: CBRC-EEUR-01-1541 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-EEUR-01-1541 gb|AAV38759.1| opiate receptor-like 1 [synthetic construct] gb|AAV38760.1| opiate... receptor-like 1 [synthetic construct] gb|AAX43081.1| opiate receptor-like 1 [synthetic construct] gb|AAX43082.1| opi...ate receptor-like 1 [synthetic construct] AAV38759.1 2e-82 88% ...

  16. NCBI nr-aa BLAST: CBRC-MDOM-01-0382 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MDOM-01-0382 gb|AAV38759.1| opiate receptor-like 1 [synthetic construct] gb|AAV38760.1| opiate... receptor-like 1 [synthetic construct] gb|AAX43081.1| opiate receptor-like 1 [synthetic construct] gb|AAX43082.1| opi...ate receptor-like 1 [synthetic construct] AAV38759.1 1e-171 79% ...

  17. The stereoisomer (+)-naloxone potentiates G-protein coupling and feeding associated with stimulation of mu opioid receptors in the parabrachial nucleus.

    Science.gov (United States)

    Chaijale, Nayla N; Aloyo, Vincent J; Simansky, Kenny J

    2013-03-01

    Classically, opioids produce their effects by activating Gi-proteins that inhibit adenylate cyclase activity. Previous studies proposed that mu-opioid receptors can also stimulate adenylate cyclase due to an initial transient coupling to Gs-proteins. Treatment with ultra-low doses of the nonselective opioid antagonist (-)-naloxone or its inactive enantiomer (+)-naloxone blocks this excitatory effect and enhances Gi-coupling. Previously we reported that infusion of the mu-opioid receptor agonist [D-Ala2, N-Me-Phe4, Glycinol5]-Enkephalin (DAMGO) into the mu-opioid receptor expressing lateral parabrachial nucleus increases feeding. Pretreatment with (-)-naloxone blocks this effect. We used this parabrachial circuit as a model to assess cellular actions of ultra-low doses of (-)-naloxone and (+)-naloxone in modifying the effects of DAMGO. Our results showed that an ultra-low concentration of (-)-naloxone (0.001 nM) and several concentrations of (+)-naloxone (0.01-10 nM) enhanced DAMGO-stimulated guanosine-5'-0-(γ-thio)-triphosphate incorporation in parabrachial sections in vitro. Further, we analyzed the relevance of these effects in vivo. In the present study, we show that (+)-naloxone can potentiate DAMGO-induced feeding at doses at which (-)-naloxone was an antagonist. These results implicated (+)-naloxone as a novel tool for studying mu-opioid receptor functions and suggest that (+)-naloxone may have therapeutic value to enhance clinical actions of opiate drugs.

  18. NCBI nr-aa BLAST: CBRC-HSAP-20-0024 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-HSAP-20-0024 ref|NP_000904.1| opiate receptor-like 1 [Homo sapiens] ref|NP_872588.1| opiate...OPRL1 protein [Homo sapiens] gb|AAP23195.1| opiate receptor-like 1 [Homo sapiens] emb|CAG46858.1| OPRL1 [Hom...o sapiens] emb|CAD11904.2| opiate receptor-like 1 [Homo sapiens] emb|CAC17003.2| opiate receptor-like 1 [Hom...o sapiens] gb|ABM84132.1| opiate receptor-like 1 [synthetic construct] gb|ABM84133.1| opiate... receptor-like 1 [synthetic construct] gb|ABW03593.1| opiate receptor-like 1 [synthetic construct] NP_000904.1 0.0 100% ...

  19. NCBI nr-aa BLAST: CBRC-CFAM-24-0010 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CFAM-24-0010 ref|NP_000904.1| opiate receptor-like 1 [Homo sapiens] ref|NP_872588.1| opiate...OPRL1 protein [Homo sapiens] gb|AAP23195.1| opiate receptor-like 1 [Homo sapiens] emb|CAG46858.1| OPRL1 [Hom...o sapiens] emb|CAD11904.2| opiate receptor-like 1 [Homo sapiens] emb|CAC17003.2| opiate receptor-like 1 [Hom...o sapiens] gb|ABM84132.1| opiate receptor-like 1 [synthetic construct] gb|ABM84133.1| opiate... receptor-like 1 [synthetic construct] gb|ABW03593.1| opiate receptor-like 1 [synthetic construct] NP_000904.1 0.0 96% ...

  20. NCBI nr-aa BLAST: CBRC-GGAL-20-0003 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GGAL-20-0003 ref|NP_000904.1| opiate receptor-like 1 [Homo sapiens] ref|NP_872588.1| opiate...OPRL1 protein [Homo sapiens] gb|AAP23195.1| opiate receptor-like 1 [Homo sapiens] emb|CAG46858.1| OPRL1 [Hom...o sapiens] emb|CAD11904.2| opiate receptor-like 1 [Homo sapiens] emb|CAC17003.2| opiate receptor-like 1 [Hom...o sapiens] gb|ABM84132.1| opiate receptor-like 1 [synthetic construct] gb|ABM84133.1| opiate... receptor-like 1 [synthetic construct] gb|ABW03593.1| opiate receptor-like 1 [synthetic construct] NP_000904.1 1e-141 66% ...

  1. NCBI nr-aa BLAST: CBRC-TGUT-23-0006 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TGUT-23-0006 ref|NP_000904.1| opiate receptor-like 1 [Homo sapiens] ref|NP_872588.1| opiate...OPRL1 protein [Homo sapiens] gb|AAP23195.1| opiate receptor-like 1 [Homo sapiens] emb|CAG46858.1| OPRL1 [Hom...o sapiens] emb|CAD11904.2| opiate receptor-like 1 [Homo sapiens] emb|CAC17003.2| opiate receptor-like 1 [Hom...o sapiens] gb|ABM84132.1| opiate receptor-like 1 [synthetic construct] gb|ABM84133.1| opiate... receptor-like 1 [synthetic construct] gb|ABW03593.1| opiate receptor-like 1 [synthetic construct] NP_000904.1 1e-141 66% ...

  2. NCBI nr-aa BLAST: CBRC-ETEL-01-0228 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-ETEL-01-0228 ref|NP_000904.1| opiate receptor-like 1 [Homo sapiens] ref|NP_872588.1| opiate...OPRL1 protein [Homo sapiens] gb|AAP23195.1| opiate receptor-like 1 [Homo sapiens] emb|CAG46858.1| OPRL1 [Hom...o sapiens] emb|CAD11904.2| opiate receptor-like 1 [Homo sapiens] emb|CAC17003.2| opiate receptor-like 1 [Hom...o sapiens] gb|ABM84132.1| opiate receptor-like 1 [synthetic construct] gb|ABM84133.1| opiate... receptor-like 1 [synthetic construct] gb|ABW03593.1| opiate receptor-like 1 [synthetic construct] NP_000904.1 1e-149 91% ...

  3. NCBI nr-aa BLAST: CBRC-TBEL-01-1256 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-TBEL-01-1256 ref|NP_000904.1| opiate receptor-like 1 [Homo sapiens] ref|NP_872588.1| opiate...OPRL1 protein [Homo sapiens] gb|AAP23195.1| opiate receptor-like 1 [Homo sapiens] emb|CAG46858.1| OPRL1 [Hom...o sapiens] emb|CAD11904.2| opiate receptor-like 1 [Homo sapiens] emb|CAC17003.2| opiate receptor-like 1 [Hom...o sapiens] gb|ABM84132.1| opiate receptor-like 1 [synthetic construct] gb|ABM84133.1| opiate... receptor-like 1 [synthetic construct] gb|ABW03593.1| opiate receptor-like 1 [synthetic construct] NP_000904.1 4e-61 91% ...

  4. NCBI nr-aa BLAST: CBRC-PABE-21-0028 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PABE-21-0028 ref|NP_000904.1| opiate receptor-like 1 [Homo sapiens] ref|NP_872588.1| opiate...OPRL1 protein [Homo sapiens] gb|AAP23195.1| opiate receptor-like 1 [Homo sapiens] emb|CAG46858.1| OPRL1 [Hom...o sapiens] emb|CAD11904.2| opiate receptor-like 1 [Homo sapiens] emb|CAC17003.2| opiate receptor-like 1 [Hom...o sapiens] gb|ABM84132.1| opiate receptor-like 1 [synthetic construct] gb|ABM84133.1| opiate... receptor-like 1 [synthetic construct] gb|ABW03593.1| opiate receptor-like 1 [synthetic construct] NP_000904.1 0.0 98% ...

  5. NCBI nr-aa BLAST: CBRC-EEUR-01-1541 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-EEUR-01-1541 ref|NP_000904.1| opiate receptor-like 1 [Homo sapiens] ref|NP_872588.1| opiate...OPRL1 protein [Homo sapiens] gb|AAP23195.1| opiate receptor-like 1 [Homo sapiens] emb|CAG46858.1| OPRL1 [Hom...o sapiens] emb|CAD11904.2| opiate receptor-like 1 [Homo sapiens] emb|CAC17003.2| opiate receptor-like 1 [Hom...o sapiens] gb|ABM84132.1| opiate receptor-like 1 [synthetic construct] gb|ABM84133.1| opiate... receptor-like 1 [synthetic construct] gb|ABW03593.1| opiate receptor-like 1 [synthetic construct] NP_000904.1 2e-82 88% ...

  6. NCBI nr-aa BLAST: CBRC-CJAC-01-0417 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CJAC-01-0417 ref|NP_000904.1| opiate receptor-like 1 [Homo sapiens] ref|NP_872588.1| opiate...OPRL1 protein [Homo sapiens] gb|AAP23195.1| opiate receptor-like 1 [Homo sapiens] emb|CAG46858.1| OPRL1 [Hom...o sapiens] emb|CAD11904.2| opiate receptor-like 1 [Homo sapiens] emb|CAC17003.2| opiate receptor-like 1 [Hom...o sapiens] gb|ABM84132.1| opiate receptor-like 1 [synthetic construct] gb|ABM84133.1| opiate... receptor-like 1 [synthetic construct] gb|ABW03593.1| opiate receptor-like 1 [synthetic construct] NP_000904.1 1e-121 99% ...

  7. NCBI nr-aa BLAST: CBRC-OANA-01-2124 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-OANA-01-2124 ref|NP_000904.1| opiate receptor-like 1 [Homo sapiens] ref|NP_872588.1| opiate...OPRL1 protein [Homo sapiens] gb|AAP23195.1| opiate receptor-like 1 [Homo sapiens] emb|CAG46858.1| OPRL1 [Hom...o sapiens] emb|CAD11904.2| opiate receptor-like 1 [Homo sapiens] emb|CAC17003.2| opiate receptor-like 1 [Hom...o sapiens] gb|ABM84132.1| opiate receptor-like 1 [synthetic construct] gb|ABM84133.1| opiate... receptor-like 1 [synthetic construct] gb|ABW03593.1| opiate receptor-like 1 [synthetic construct] NP_000904.1 1e-150 69% ...

  8. NCBI nr-aa BLAST: CBRC-DNOV-01-1501 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-1501 ref|NP_000904.1| opiate receptor-like 1 [Homo sapiens] ref|NP_872588.1| opiate...OPRL1 protein [Homo sapiens] gb|AAP23195.1| opiate receptor-like 1 [Homo sapiens] emb|CAG46858.1| OPRL1 [Hom...o sapiens] emb|CAD11904.2| opiate receptor-like 1 [Homo sapiens] emb|CAC17003.2| opiate receptor-like 1 [Hom...o sapiens] gb|ABM84132.1| opiate receptor-like 1 [synthetic construct] gb|ABM84133.1| opiate... receptor-like 1 [synthetic construct] gb|ABW03593.1| opiate receptor-like 1 [synthetic construct] NP_000904.1 1e-152 92% ...

  9. An efficient synthesis of 3-OBn-6β,14-epoxy-bridged opiates from naltrexone and identification of a related dual MOR inverse agonist/KOR agonist.

    Science.gov (United States)

    Martin, David J; FitzMorris, Paul E; Li, Bo; Ayestas, Mario; Sally, Ellicott J; Dersch, Christina M; Rothman, Richard B; Deveau, Amy M

    2012-11-15

    In an effort to better understand the conformational preferences that inform the biological activity of naltrexone and related naltrexol derivatives, a new synthesis of the restricted analog 3-OBn-6β,14-epoxymorphinan 4 is described. 4 was synthesized starting from naltrexone in 50% overall yield, proceeding through the OBn-6α-triflate intermediate 8. Key steps to the synthesis include benzylation (96% yield), reduction (90% yield, α:β:3:2), followed by a one-pot triflation/displacement sequence (96% yield) to yield the desired bridged epoxy derivative 4. X-ray crystallographic analysis of intermediate 3-OBn-6α-naltrexol 7a supports population of the key boat conformation required for the epoxy ring closure. We also report that the 6β-mesylate 10-a high affinity opioid receptor ligand, the epimeric derivative of 11, and an analog of 12-functions as an inverse agonist at the mu opioid receptor using herkinorin pre-conditioned cells and an agonist at the kappa opioid receptor when evaluated in independent in vitro [(35)S]-GTP-γ-S assays.

  10. GABA receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, GABA{sub A}-receptor that allows chloride to pass through a ligand gated ion channel and GABA{sub B}-receptor that uses G-proteins for signaling. The GABA{sub A}-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate GABA{sub A}-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with {sup 11}C-FMZ, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, {sup 18}F-fluoroflumazenil (FFMZ) has been developed to overcome {sup 11}C's short half-life. {sup 18}F-FFMZ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using '1{sup 1}C-FMZ PET instead of {sup 18}F-FDG, PET, restrict the foci better and may also help find lesions better than high resolution MR. GABA{sub A} receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, GABA imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

  11. 阿片受体泛素化机制及其对受体功能的影响%Mechanism of opioid receptor ubiquitination and its effect on receptor function

    Institute of Scientific and Technical Information of China (English)

    江洁冰; 周培岚; 郑志兵; 苏瑞斌

    2015-01-01

    Opioid receptors, as an important member of G protein coupled receptors (GPCR), are the binding targets of endogenous opioid peptides and exogenous opiates. The activation of opioid receptors influences the nervous system, immune physiology and endocrine system. However, prolonged activation of opioid receptors is likely to produce opioid tolerance, leading to opioid addiction. Receptor endocytosis and sorting into the recycling pathway contribute to recovery of cellular opioid responsiveness. Recent studies have revealed that GPCR can be modulated by ubiquitination which plays a unique roles in governing GPCR trafficking. Moreover, ubiquitination of the opioid receptors (μ, κand δ) is increased after stimulation of most opioid agonists. Mutation of the ubiquitin sites affects the internalization and degradation of opioid receptors, which contributes to changes in signal pathways and regulation of opioid receptors. ln this paper, ubiquitination of opioid receptors and the fundamental role of ubiquitination in trafficking of opioid receptors are reviewed.%阿片受体是一类重要的 G 蛋白偶联受体(GPCR),是内源性阿片肽及阿片类药物结合的靶点,阿片受体激活后对神经系统、免疫及内分泌系统具有调节作用。但阿片受体在反复激活后,容易出现耐受,导致阿片成瘾。受体的内吞和再循环对受体复敏具有重要意义。近年来研究发现,受体的泛素化修饰参与了 GPCR 的转运过程,并且多数配体作用于阿片受体后,受体的泛素化水平明显升高。将阿片受体的泛素化位点突变后,对不同阿片受体亚型的内吞和降解过程产生了不同的影响,进而影响了阿片受体的信号转导过程。本文着重对阿片受体3种亚型的泛素化修饰特点及泛素化对受体转运的调节作用进行综述。

  12. Chicken NK cell receptors.

    Science.gov (United States)

    Straub, Christian; Neulen, Marie-Luise; Sperling, Beatrice; Windau, Katharina; Zechmann, Maria; Jansen, Christine A; Viertlboeck, Birgit C; Göbel, Thomas W

    2013-11-01

    Natural killer cells are innate immune cells that destroy virally infected or transformed cells. They recognize these altered cells by a plethora of diverse receptors and thereby differ from other lymphocytes that use clonally distributed antigen receptors. To date, several receptor families that play a role in either activating or inhibiting NK cells have been identified in mammals. In the chicken, NK cells have been functionally and morphologically defined, however, a conclusive analysis of receptors involved in NK cell mediated functions has not been available. This is partly due to the low frequencies of NK cells in blood or spleen that has hampered their intensive characterization. Here we will review recent progress regarding the diverse NK cell receptor families, with special emphasis on novel families identified in the chicken genome with potential as chicken NK cell receptors. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Novel cannabinoid receptors

    OpenAIRE

    Brown, A J

    2007-01-01

    Cannabinoids have numerous physiological effects. In the years since the molecular identification of the G protein-coupled receptors CB1 and CB2, the ion channel TRPV1, and their corresponding endogenous ligand systems, many cannabinoid-evoked actions have been shown conclusively to be mediated by one of these specific receptor targets. However, there remain several examples where these classical cannabinoid receptors do not explain observed pharmacology. Studies using mice genetically delete...

  14. Therapeutic androgen receptor ligands

    OpenAIRE

    Allan, George F.; Sui, Zhihua

    2003-01-01

    In the past several years, the concept of tissue-selective nuclear receptor ligands has emerged. This concept has come to fruition with estrogens, with the successful marketing of drugs such as raloxifene. The discovery of raloxifene and other selective estrogen receptor modulators (SERMs) has raised the possibility of generating selective compounds for other pathways, including androgens (that is, selective androgen receptor modulators, or SARMs).

  15. Utilización del citrato de fentanilo oral transmucosa como rescate terapéutico en pacientes con altas dosis de opioides Use of oral transmucosal fentanyl citrate for therapeutic rescue in patients receiving high doses of opiates

    Directory of Open Access Journals (Sweden)

    J. Cevas

    2005-07-01

    crisis de DI en pacientes oncológicos que tienen controlado su dolor basal con dosis altas de opioides. Las dosis de CFOT pueden considerarase como bajas en relación a las utilizadas para su dolor basal. Su administración y titulación es sencilla, aunque el paciente requiere de una educación previa a su uso.The management of breakthrough pain in cancer patients treated with high doses of opiates raises particular problems, such as the election of the drug to be used, the appropriate dosage and the route of administration. No clear guidelines on this issue are found in the medical literature, so each service decides its own particular way of acting. In this paper we review the cases dealt with over a one-year period in terms of the use of high doses of opiates in cancer patients taken care of in 2003 and treated with opiates. Objectives: -To study the group of patients treated with high doses of opiates. -To use OTFC as rescue drug for breakthrough pain events. -To analyze side and toxic effects. -To determine the preferences of the patients. Material and methods: A population of 280 patients with advanced cancer, 25 of which were receiving high doses of opiates. In these patients, breakthrough pain crises were managed with OTFC, starting with 400 micrograms. The satisfaction questionnaire proposed by Kornick was used. Results: -Easy adherence to treatment. -Average effective dose of OTFC: 600 micrograms, median of 627. -Dose titration on the second day. -Seventeen patients preferred OTFC, 6 preferred oral morphine and 2 were indifferent. Conclusions: Easy use of OTFC for the management of breakthrough pain, requiring low doses compared to the total daily dose of the patient. Patient education is required before its administration.

  16. NMDA受体在痛敏与阿片类药依赖和耐受中的作用%The Role of NMDA Receptor in Hyperalgesia and opiate dependence and tolerance

    Institute of Scientific and Technical Information of China (English)

    刘惠芬; 周文华; 杨国栋

    2004-01-01

    近来阿片类药的镇痛与成瘾机制的研究进展非常迅速,多种受体及相应配体参与阿片类药的镇痛和成瘾。NMDA受体在体内参与许多复杂的生理和病理机制。近年实验研究表明NMDA受体除参与学习和记忆,突触的可塑性,缺血缺氧导致的兴奋性作用等外,也参与镇痛的调制和阿片类药依赖与耐受的形成。

  17. AMPA receptor ligands

    DEFF Research Database (Denmark)

    Strømgaard, Kristian; Mellor, Ian

    2004-01-01

    Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the f......Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...

  18. Kinetic analysis of transport and opioid receptor binding of ( sup 3 H)(-)-cyclofoxy in rat brain in vivo: Implications for human studies

    Energy Technology Data Exchange (ETDEWEB)

    Sawada, Y.; Kawai, R.; McManaway, M.; Otsuki, H.; Rice, K.C.; Patlak, C.S.; Blasberg, R.G. (National Institutes of Health, Bethesda, MD (USA))

    1991-03-01

    (3H)Cyclofoxy (CF: 17-cyclopropylmethyl-3,14-dihydroxy-4,5-alpha-epoxy-6-beta-fluoromorp hinan) is an opioid antagonist with affinity to both mu and kappa subtypes that was synthesized for quantitative evaluation of opioid receptor binding in vivo. Two sets of experiments in rats were analyzed. The first involved determining the metabolite-corrected blood concentration and tissue distribution of CF in brain 1 to 60 min after i.v. bolus injection. The second involved measuring brain washout for 15 to 120 s following intracarotid artery injection of CF. A physiologically based model and a classical compartmental pharmacokinetic model were compared. The models included different assumptions for transport across the blood-brain barrier (BBB); estimates of nonspecific tissue binding and specific binding to a single opiate receptor site were found to be essentially the same with both models. The nonspecific binding equilibrium constant varied modestly in different brain structures (Keq = 3-9), whereas the binding potential (BP) varied over a much broader range (BP = 0.6-32). In vivo estimates of the opioid receptor dissociation constant were similar for different brain structures (KD = 2.1-5.2 nM), whereas the apparent receptor density (Bmax) varied between 1 (cerebellum) and 78 (thalamus) pmol/g of brain. The receptor dissociation rate constants in cerebrum (k4 = 0.08-0.16 min-1; koff = 0.16-0.23 min-1) and brain vascular permeability (PS = 1.3-3.4 ml/min/g) are sufficiently high to achieve equilibrium conditions within a reasonable period of time. Graphical analysis of the data is inappropriate due to the high tissue-loss rate constant for CF in brain. From these findings, CF should be a very useful opioid receptor ligand for the estimation of the receptor binding parameters in human subjects using (18F)CF and positron emission tomography.

  19. Differential effects of dopamine and opioid receptor blockade on motivated Coca-Cola drinking behavior and associated changes in brain, skin and muscle temperatures.

    Science.gov (United States)

    Kiyatkin, E A

    2010-05-05

    Although pharmacological blockade of both dopamine (DA) and opiate receptors has an inhibiting effect on appetitive motivated behaviors, it is still unclear which physiological mechanisms affected by these treatments underlie the behavioral deficit. To clarify this issue, we examined how pharmacological blockade of either DA (SCH23390+eticlopride at 0.2 mg/kg each) or opioid receptors (naloxone 1 mg/kg) affects motor activity and temperature fluctuations in the nucleus accumbens (NAcc), temporal muscle, and facial skin associated with motivated Coca-Cola drinking behavior in rats. In drug-free conditions, presentation of a cup containing 5 ml of Coca-Cola induced locomotor activation and rapid NAcc temperature increases, which both transiently decreased during drinking, and phasically increased again after the cup was emptied. Muscle temperatures followed this pattern, but increases were weaker and more delayed than those in the NAcc. Skin temperature rapidly dropped after cup presentation, remained at low levels during consumption, and slowly restored during post-consumption behavioral activation. By itself, DA receptor blockade induced robust decrease in spontaneous locomotion, moderate increases in brain and muscle temperatures, and a relative increase in skin temperatures, suggesting metabolic activation coupled with adynamia. Following this treatment (approximately 180 min), motor activation to cup presentation and Coca-Cola consumption were absent, but rats showed NAcc and muscle temperature increases following cup presentation comparable to control. Therefore, DA receptor blockade does not affect significantly central and peripheral autonomic responses to appetitive stimuli, but eliminates their behavior-activating effects, thus disrupting appetitive behavior and blocking consumption. Naloxone alone slightly decreased brain and muscle temperatures and increased skin temperatures, pointing at the enhanced heat loss and possible minor inhibition of basal

  20. Intra-accumbal CB1 receptor blockade reduced extinction and reinstatement of morphine.

    Science.gov (United States)

    Khaleghzadeh-Ahangar, Hossein; Haghparast, Abbas

    2015-10-01

    The limbic dopaminergic reward system is the main target of morphine-like drugs which begins from the ventral tegmental area (VTA) and sends its dopaminergic projections to the nucleus accumbens (NAc), amygdala, hippocampus and prefrontal cortex. Cannabinoid receptors exist in afferent neurons from these areas to the NAc and can modulate glutamate synaptic transmission in the NAc. Cannabinoids can interact with the opiate system in reward-related behaviors; nevertheless these systems' interaction in extinction duration and reinstatement has not been shown. In the present study, the effects of bilateral intra-accumbal administration of AM251, a CB1 receptor antagonist, on the duration of the extinction phase and reinstatement to morphine were investigated by conditioned place preference (CPP) paradigm. Forty eight adult male albino Wistar rats were used. Bilateral intra-accumbal administration of AM251 (15, 45 and 90μM/0.5μl DMSO per side) was performed. Subcutaneous administration of morphine (5mg/kg) in three consecutive days was used to induce CPP. The results showed that administration of the maximal dose of AM251 during the extinction period significantly reduces duration of extinction and reinstatement to morphine. Administration of the middle dose during the extinction period significantly attenuated reinstatement to morphine. A single microinjection of the middle dose just before the reinstatement phase significantly attenuated reinstatement to morphine only, while bilateral intra-accumbal administration of neither the lowest dose nor the vehicle (DMSO) had any effects. These results for the first time indicated that CB1 receptors within the NAc are involved in the maintenance of morphine rewarding properties, and morphine seeking behaviors in extinguished morphine-induced CPP rats.

  1. 手术戒毒患者术后生命质量与社会支持调查分析%AN ANALYSIS OF QUALITY OF LIFE AND SOCIAL SUPPORT AMONG THE OPIATE USERS AFTER ABSTINENCE BY STEREOTACTIC NEUROSURGERY

    Institute of Scientific and Technical Information of China (English)

    张本

    2009-01-01

    目的:探讨阿片类药物依赖患者在接受立体定向治疗手术一年后,其生命质量和社会支持情况.方法:设立手术组、非手术组、健康对照组,填写相关量表调查3组人群的生命质量与社会支持情况,采用方差分析及多重比较法分析,比较手术组和非手术组通过不同的戒毒治疗方法,一年后的生命质量和社会支持情况,比较术后一年手术组中的复吸与非复吸者的生命质量与社会支持情况,并分别与健康对照组相比较.结果:手术组患者术后一年的生命质量优于非手术组,但仍不及健康对照组,术后一年复吸者的生命质量低于未复吸者;手术组患者术后一年的社会支持优于非手术组,但仍不及健康对照组,术后一年复吸者得到的社会支持比未复吸者少.结论:相比传统的戒毒方法,手术戒毒更有利于提高患者的生命质量及获得更多的社会支持,也有助于降低复吸率.手术戒毒患者术后一年的生命质量及社会支持与健康人群相比仍有一定差距,需通过进一步的综合治疗尽快回归正常生活.%Objective:To probe into the quality of life and social support of the opiate users after abstinence by stereotactic neurosurgery. Methods:Questionnaires have been handed out to the surgical group, non-surgical group and healthy person group. We used statistical methods of ANOVA and LSD to compare the quality of life(QOL) and social support among these 3 groups. The relapsed and un-relapsed patients in surgical group were also taken into consideration. Results:In post-operation more than one year, the QOL of patients in surgical group was better than the non-surgical patients, but still worse compared with the healthy person group. Likewise, the patients in surgical group experienced more social support than the non-surgical group, which would be helpful for drug abstinence. Conclusion:Stereotactic neurosurgery and a series of auxiliary therapies in post

  2. [The LDL receptor family].

    Science.gov (United States)

    Meilinger, Melinda

    2002-12-29

    The members of the LDL receptor family are structurally related endocytic receptors. Our view on these receptors has considerably changed in recent years. Not only have new members of the family been identified, but also several interesting observations have been published concerning the biological function of these molecules. The LDL receptor family members are able to bind and internalize a plethora of ligands; as a consequence, they play important roles in diverse physiological processes. These receptors are key players in the lipoprotein metabolism, vitamin homeostasis, Ca2+ homeostasis, cell migration, and embryonic development. Until recently, LDL receptor family members were thought to be classic endocytic receptors that provide cells with metabolites on one hand, while regulating the concentration of their ligands in the extracellular fluids on the other hand. However, recent findings indicate that in addition to their cargo transport function, LDL receptor family members can act as signal transducers, playing important roles in the development of the central nervous system or the skeleton. Better understanding of physiological and pathophysiological functions of these molecules may open new avenues for the treatment or prevention of many disorders.

  3. 美沙酮维持治疗门诊病人滥用"冰毒"行为调查%INVESTIGATION ON METHAMPHETAMINE ABUSE AMONG OPIATE ADDICTS UNDER METHADONE MAINTENANCE TREATMENT

    Institute of Scientific and Technical Information of China (English)

    伏新艳; 高菁; 潘蕾; 方欣; 车驰

    2012-01-01

    Objective: To understand the situation of methamphetamine abuse among opiate addicts during methadone maintenance treatmen( MMT) , found possible risk of drug abuse among them and provide scientific data for the improvement of MMT. Methods: A survey was conducted on 462 patients in 4 MMT clinics with a self - designed questionnaire, the main contents of which were general conditions, drug abuse and physical status of the patients. Urine tests were also made for amphetamine use ( colloidal gold rapid detection ) . Results: Among 462 cases, 86 cases were amphetamine urine test positive, the positive rate was 18. 61% , with male s positive rate 18.52% and female s positive rate 19.05%. The chi -square test showed that there was no significant difference at variables of gender, age, marital status, occupation classification, level of education, between subjects with amphetamine urine test positive and those with negative urine test. Conclusion: There exists amphetamine abuse phenomenon among opiate addicts on MMT.%目的:了解接受美沙酮维持治疗(methadone maintenance treatment.MMT)的阿片类药物成瘾者接受MMT期间是否存在滥用"冰毒"的行为及发生率,为有关部门及时掌握可能存在的隐匿药物滥用风险,为进一步完善MMT措施提供客观数据与科学建议.方法:采用自编的对某地4所美沙酮维持治疗门诊收治的462名患者进行问卷调查,并对调查对象进行苯丙胺类尿检(胶体金法快速检测).结果:462例被调查对象中苯丙胺类尿检阳性86例,阳性检出率达18.61%,其中,男性阳性率占18.52%,女性阳性率占19.05%.X2检验结果显示,男女性别、年龄、婚姻状况、职业、受教育程度尿检阳性率的差异均无统计学意义(P>0.05).结论:接受美沙酮维持治疗的阿片类药物成瘾者有滥用冰毒的现象.

  4. Glutamate receptor agonists

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Greenwood, Jeremy R; Bunch, Lennart;

    2011-01-01

    The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally a-amino acids with one or more...... stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses...... mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist...

  5. Activation of P2X7 receptors in the midbrain periaqueductal gray of rats facilitates morphine tolerance.

    Science.gov (United States)

    Xiao, Zhi; Li, You-Yan; Sun, Meng-Jie

    2015-08-01

    Opiates such as morphine exhibit analgesic effect in various pain models, but repeated and chronic morphine administration may develop resistance to antinociception. The purinergic signaling system is involved in the mechanisms of pain modulation and morphine tolerance. This study aimed to determine whether the P2X7 receptor in the ventrolateral midbrain periaqueductal gray (vlPAG) is involved in morphine tolerance. Development of tolerance to the antinociceptive effect of morphine was induced in normal adult male Sprague-Dawley (SD) rats through subcutaneous injection of morphine (10mg/kg). The analgesic effect of morphine (5mg/kg, i.p.) was assessed by measuring mechanical withdrawal thresholds (MWTs) in rats with an electronic von Frey anesthesiometer. The expression levels and distribution of the P2X7 receptor in the vlPAG was evaluated through Western blot analysis and immunohistochemistry. The acute effects of intra-vlPAG injection of the selective P2X7 receptor agonist Bz-ATP, the selective P2X7 receptor antagonist A-740003, or antisense oligodeoxynucleotide (AS ODN) targeting the P2X7 receptor on morphine-treated rats were also observed. Results demonstrated that repeated morphine administration decreased the mechanical pain thresholds. By contrast, the expression of the P2X7 receptor protein was up-regulated in the vlPAG in morphine tolerant rats. The percent changes in MWT were markedly but only transiently attenuated by intra-vlPAG injection of Bz-ATP (9nmol/0.3μL) but elevated by A-740003 at doses of 10 and 100nmol/0.3μL. AS ODN (15nmol/0.3μL) against the P2X7 receptor reduced the development of chronic morphine tolerance in rats. These results suggest that the development of antinociceptive tolerance to morphine is partially mediated by activating the vlPAG P2X7 receptors. The present data also suggest that the P2X7 receptors may be a therapeutic target for improving the analgesic effect of morphine in treatments of pain when morphine tolerance

  6. Protein receptor for activated C kinase 1 is involved in morphine reward in mice.

    Science.gov (United States)

    Wan, L; Su, L; Xie, Y; Liu, Y; Wang, Y; Wang, Z

    2009-07-07

    Opiate addiction is associated with upregulation of cAMP signaling in the brain. cAMP-responsive element binding protein (CREB), a nuclear transcription factor, is a downstream component of the extracellular signal-regulated protein kinase (ERK) pathway, which has been shown to regulate different physiological and psychological responses of drug addiction. RACK1, the protein receptor for activated C kinase 1, is a multifunctional scaffolding protein known to be a key regulator of various signaling cascades in the CNS. RACK1 functions specifically in integrin mediated activation of ERK cascade and targets active ERK. We examined if RACK1 is involved in the mechanism of drug addiction by regulating CREB in mouse hippocampus and prefrontal cortex. Several expressions were observed. Chronic administration of morphine made the expression of RACK1 and CREB mRNA increase in hippocampus and prefrontal cortex. The expression of RACK1 and CREB protein was strongly positive in CA1, CA3 and dentate gyrus (DG) of the hippocampus of morphine-treated mice brain, especially the pyramidal neurons in the DG of the hippocampus. Using the small interfering RNA technology, we determined that the expression of CREB mRNA was decreased in hippocampus and prefrontal cortex of morphine-treated mice. The expression of RACK1 and CREB protein was negative in CA1, CA3 and DG of hippocampus. These findings suggest that morphine reward can influence the expression of RACK1 in mouse hippocampus and prefrontal cortex through regulating CREB transcription.

  7. Morphine conditioned place preference depends on glucocorticoid receptors in both hippocampus and nucleus accumbens.

    Science.gov (United States)

    Dong, Zhifang; Han, Huili; Wang, Meina; Xu, Lin; Hao, Wei; Cao, Jun

    2006-01-01

    Learned association between drugs of abuse and context is essential for the formation of drug conditioned place preference (CPP), which is believed to engage many brain regions including hippocampus and nucleus accumbens (NAc). The underlying mechanisms are not fully understood. Here, we examined whether glucocorticoid receptors (GRs) of hippocampus and NAc influenced the formation of morphine CPP in Sprague Dawley rats. We found that systemic or intrahippocampal infused DMSO vehicle (DMSO 20% in saline) 30 min before daily morphine (10 mg/kg, s.c.) conditioning did not affect the formation of morphine CPP. In contrast, systemic administration (5 mg/kg, s.c.) or intrahippocampal infusion (0, 0.1, 1.0, 10, 20 microg per side) of the GR antagonist RU38486 blocked or impaired the formation of CPP in a dose-dependent manner, respectively. Furthermore, intra-NAc infused RU38486 (10 microg per side) but not DMSO vehicle also prevented the formation of CPP. These results demonstrate that both the GRs of hippocampus and NAc are necessary for the formation of morphine CPP, suggesting a neural network function of the GRs in forming the opiate-associated memory.

  8. Relación del efecto analgésico de fentanilo agudo con la regulación a la alta de los receptores 5-HT1A cerebrales en la rata Relationship between the analgesic effect of acute fentanyl and upregulation of brain 5-HT1A receptors in the rat

    Directory of Open Access Journals (Sweden)

    I. Bellido

    2004-07-01

    of opiate neurotransmission acting directly on opiate µ receptors and the increase of 5-HT levels at the central nervous system and the up-regulation of 5-HT1A receptors at the terminal brain areas, hence facilitating the stimulation of such receptors. Since the post-synaptic 5-HT1A receptors act as heteroreceptors that inhibit non-serotoninergic neurons and cause neuronal hyperpolarization, fentanyl would facilitate the stimulation of these receptors and would inhibit the neuronal activity in all such terminal areas, preventing the transmission of the nociceptive stimulus. This would explain the reduced analgesic effect of opiate µ agonists that is observed with selective 5-HT1A antagonists and the increased analgesic effect observed when µ agonists and other drugs capable of increasing 5-HT levels, such as ISRS, are co-administered. Further studies are required in order to accurately determine the mechanism through which the stimulation of µ receptors cause up-regulation of post-synaptic 5-HT1A receptors and the role of each brain area in the perception of the nociceptive stimulus.

  9. Delta opioid receptor on equine sperm cells: subcellular localization and involvement in sperm motility analyzed by computer assisted sperm analyzer (CASA

    Directory of Open Access Journals (Sweden)

    Lacalandra Giovanni M

    2010-06-01

    Full Text Available Abstract Background Opioid receptors and endogenous opioid peptides act not only in the control of nociceptive pathways, indeed several reports demonstrate the effects of opiates on sperm cell motility and morphology suggesting the importance of these receptors in the modulation of reproduction in mammals. In this study we investigated the expression of delta opioid receptors on equine spermatozoa by western blot/indirect immunofluorescence and its relationship with sperm cell physiology. Methods We analyzed viability, motility, capacitation, acrosome reaction and mitochondrial activity in the presence of naltrindole and DPDPE by means of a computer assisted sperm analyzer and a fluorescent confocal microscope. The evaluation of viability, capacitation and acrosome reaction was carried out by the double CTC/Hoechst staining, whereas mitochondrial activity was assessed by means of MitoTracker Orange dye. Results We showed that in equine sperm cells, delta opioid receptor is expressed as a doublet of 65 and 50 kDa molecular mass and is localized in the mid piece of tail; we also demonstrated that naltrindole, a delta opioid receptor antagonist, could be utilized in modulating several physiological parameters of the equine spermatozoon in a dose-dependent way. We also found that low concentrations of the antagonist increase sperm motility whereas high concentrations show the opposite effect. Moreover low concentrations hamper capacitation, acrosome reaction and viability even if the percentage of cells with active mitochondria seems to be increased; the opposite effect is exerted at high concentrations. We have also observed that the delta opioid receptor agonist DPDPE is scarcely involved in affecting the same parameters at the employed concentrations. Conclusions The results described in this paper add new important details in the comprehension of the mammalian sperm physiology and suggest new insights for improving reproduction and for

  10. Effects of chronic delta-9-tetrahydrocannabinol (THC) administration on neurotransmitter concentrations and receptor binding in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Ali, S.F.; Newport, G.D.; Scallet, A.C.; Gee, K.W.; Paule, M.G.; Brown, R.M.; Slikker, W. Jr. (National Center for Toxicological Research, Jefferson, Arkansas (USA))

    THC is the major psychoactive constituent of marijuana and is also known as an hallucinogenic compound. Numerous reports have shown that large doses of THC produce significant alterations in various neurotransmitter systems. The present study was designed to determine whether chronic exposure to THC produces significant alterations in selected neurotransmitter systems (dopamine, serotonin, acetylcholine, GABAergic, benzodiazepine, and opiate) in the rat brain. In Experiment 1, male Sprague-Dawley rats were gavaged with vehicle, 10 or 20 mg THC/kg body weight daily, 5 days/week for 90 days. Animals were killed either 24 hours or two months after the last dose. Brains were dissected into different regions for neurochemical analyses. Two months after the cessation of chronic administration, there was a significant decrease in GABA receptor binding in the hippocampus of animals in the high dose group. However, no other significant changes were found in neurotransmitter receptor binding characteristics in the hippocampus or in neurotransmitter concentrations in the caudate nucleus, hypothalamus or septum after chronic THC administration. In an attempt to replicate the GABA receptor binding changes and also to determine the (35S)TBPS binding in hippocampus, we designed Experiment 2. In this experiment, we dosed the animals by gavage with 0, 5, 10 or 20 mg THC/kg daily, 5 days/week or with 20 mg THC/kg Monday through Thursday and 60 mg/kg on Friday for 90 days. Results from this experiment failed to replicate the dose-dependent effect of THC on GABA receptor binding in hippocampus. Modulation of (35S)TBPS binding by GABA or 3 alpha-OH-DHP or inhibition by cold TBPS in frontal cortex did not show any significant dose-related effects.

  11. Mu Opioid Receptor Modulation of Dopamine Neurons in the Periaqueductal Gray/Dorsal Raphe: A Role in Regulation of Pain.

    Science.gov (United States)

    Li, Chia; Sugam, Jonathan A; Lowery-Gionta, Emily G; McElligott, Zoe A; McCall, Nora M; Lopez, Alberto J; McKlveen, Jessica M; Pleil, Kristen E; Kash, Thomas L

    2016-07-01

    The periaqueductal gray (PAG) is a brain region involved in nociception modulation, and an important relay center for the descending nociceptive pathway through the rostral ventral lateral medulla. Given the dense expression of mu opioid receptors and the role of dopamine in pain, the recently characterized dopamine neurons in the ventral PAG (vPAG)/dorsal raphe (DR) region are a potentially critical site for the antinociceptive actions of opioids. The objectives of this study were to (1) evaluate synaptic modulation of the vPAG/DR dopamine neurons by mu opioid receptors and to (2) dissect the anatomy and neurochemistry of these neurons, in order to assess the downstream loci and functions of their activation. Using a mouse line that expresses eGFP under control of the tyrosine hydroxylase (TH) promoter, we found that mu opioid receptor activation led to a decrease in inhibitory inputs onto the vPAG/DR dopamine neurons. Furthermore, combining immunohistochemistry, optogenetics, electrophysiology, and fast-scan cyclic voltammetry in a TH-cre mouse line, we demonstrated that these neurons also express the vesicular glutamate type 2 transporter and co-release dopamine and glutamate in a major downstream projection structure-the bed nucleus of the stria terminalis. Finally, activation of TH-positive neurons in the vPAG/DR using Gq designer receptors exclusively activated by designer drugs displayed a supraspinal, but not spinal, antinociceptive effect. These results indicate that vPAG/DR dopamine neurons likely play a key role in opiate antinociception, potentially via the activation of downstream structures through dopamine and glutamate release.

  12. Efficacy, adherence and tolerability of once daily tenofovir DF-containing antiretroviral therapy in former injecting drug users with HIV-1 receiving opiate treatment: results of a 48-week open-label study

    Directory of Open Access Journals (Sweden)

    Esser S

    2011-10-01

    Full Text Available Abstract Objective To assess efficacy, adherence and tolerability of once daily antiretroviral therapy containing tenofovir disoproxil fumarate (DF 300 mg in HIV-1-infected former injecting drug users receiving opiate treatment (IVDU. Methods European, 48-week, open-label, single-arm, multicenter study. Patients were either antiretroviral therapy-naïve, restarting therapy after treatment discontinuation without prior virological failure or switching from existing stable treatment. Results Sixty-seven patients were enrolled in the study and 41 patients completed treatment. In the primary analysis (intent-to-treat missing = failure at week 48, 34% of patients (23/67; 95% CI: 23%-47% had plasma HIV-1 RNA 3. Although self-reported adherence appeared high, there were high levels of missing data and adherence results should be treated with caution. No new safety issues were identified. Conclusions Levels of missing data were high in this difficult-to-treat population, but potent antiretroviral suppression was achieved in a substantial proportion of HIV-infected IVDU-patients.

  13. A quantitative, selective and fast ultra-high performance liquid chromatography tandem mass spectrometry method for the simultaneous analysis of 33 basic drugs in hair (amphetamines, cocaine, opiates, opioids and metabolites).

    Science.gov (United States)

    Fernández, María Del Mar Ramírez; Di Fazio, Vincent; Wille, Sarah M R; Kummer, Natalie; Samyn, Nele

    2014-08-15

    Forensic testing for drugs of abuse in hair has become a useful diagnostic tool in determining chronic drug use as well as examining long-term drug history thorough segmental analysis. However, sensitive and specific analytical methods are needed. A simple, rapid and highly sensitive and specific method for the extraction and quantification of 33 opioids, opiates, cocaine, and amphetamines is presented. The method was fully validated according to international guidelines. Twenty milligrams of hair sample was pulverized and then incubated in the same disposable tube with methanol (under sonication at 45°C) during 4h. After centrifugation the supernatant was evaporated up to about 100 μL and a solid phase extraction (SPE) followed by separation and quantification using ultra performance liquid chromatography-tandem mass spectrometry (UHLC-MS/MS) were carried out. Chromatographic separation was achieved using a BEH phenyl column eluted with 0.1% formic acid: methanol (0.1% formic acid). Selectivity of the method was achieved by a combination of retention time, and two precursor-product ion transitions. Good intra-assay and inter-assay precision (relative standard deviations (RSDs) were observed (hair samples obtained from forensic and toxicology cases and to proficiency test (obtaining z-scores lower than 1 for most of the compounds). The validation and actual sample analysis results show that this method is rugged, precise, accurate, and well-suited for routine hair analysis.

  14. Serotonin receptors in hippocampus.

    Science.gov (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system.

  15. Serotonin Receptors in Hippocampus

    Directory of Open Access Journals (Sweden)

    Laura Cristina Berumen

    2012-01-01

    Full Text Available Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system.

  16. Dopamine receptor and hypertension.

    Science.gov (United States)

    Zeng, Chunyu; Eisner, Gilbert M; Felder, Robin A; Jose, Pedro A

    2005-01-01

    Dopamine plays an important role in the pathogenesis of hypertension by regulating epithelial sodium transport and reactive oxygen and by interacting with vasopressin, renin-angiotensin, and the sympathetic nervous system. Decreased renal dopamine production and/or impaired dopamine receptor function have been reported in hypertension. Disruption of any of the dopamine receptors (D(1), D(2), D(3), D(4), and D(5)) results in hypertension. In this paper, we review the mechanisms by which hypertension develops when dopamine receptor function is perturbed.

  17. Serotonin Receptors in Hippocampus

    Science.gov (United States)

    Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

  18. Recognition receptors in biosensors

    CERN Document Server

    Zourob, Mohammed

    2010-01-01

    This book presents a significant and up-to-date review of the various recognition receptors, their immobilization, and an overview of the used surface characterization techniques. It includes more than 150 illustrations that help explain the ideas presented.

  19. Somatostatin receptor skintigrafi

    DEFF Research Database (Denmark)

    Rasmussen, Karin; Nielsen, Jørn Theil; Rehling, Michael

    2005-01-01

    Somatostatin receptor scintigraphy (SRS) is a very valuable imaging technique for visualisation of a diversity of neuroendocrine tumours. The sensitivity for localisation of carcinoid tumours is high, but somewhat lower for other neuroendocrine tumours. The methodology, multiple clinical aspects...

  20. Update on Melatonin Receptors. IUPHAR Review. : Melatonin Receptors

    OpenAIRE

    Jockers, Ralf; Delagrange, Philippe; Dubocovich, Margarita ,; Markus, Regina ,; Renault, Nicolas; Tosini, Gianluca; Cecon, Erika; Zlotos, Darius Paul

    2016-01-01

    International audience; Melatonin receptors are seven transmembrane-spanning proteins belonging to the G protein-coupled receptor super-family. In mammals, two melatonin receptor subtypes exit MT1 and MT2 encoded by the MTNR1A and MTNR1B genes, respectively. The current review provides an update on melatonin receptors by the corresponding sub-committee of the International Union of Basic and Clinical Pharmacology. We will highlight recent developments of melatonin receptor ligands, including ...

  1. Serotonin Receptors in Hippocampus

    OpenAIRE

    Laura Cristina Berumen; Angelina Rodríguez; Ricardo Miledi; Guadalupe García-Alcocer

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a fu...

  2. Receptors for enterovirus 71

    OpenAIRE

    Yamayoshi, Seiya; Fujii, Ken; Koike, Satoshi

    2014-01-01

    Enterovirus 71 (EV71) is one of the major causative agents of hand, foot and mouth disease (HFMD). Occasionally, EV71 infection is associated with severe neurological diseases, such as acute encephalitis, acute flaccid paralysis and cardiopulmonary failure. Several molecules act as cell surface receptors that stimulate EV71 infection, including scavenger receptor B2 (SCARB2), P-selectin glycoprotein ligand-1 (PSGL-1), sialylated glycan, heparan sulfate and annexin II (Anx2). SCARB2 plays crit...

  3. Estimation of BDNF gene polymorphism and predisposition to dependence development for selected psychoactive compounds: genetic aspects of addiction with the selected drugs, amphetamine, tetrahydrocannabinol and opiates.

    Science.gov (United States)

    Biskupska, J; Borowiak, K S; Karlin-Grazewicz, K; Janus, T; Waloszczyk, P; Potocka-Banas, B; Machoy-Mokrzynska, A; Ossowski, A; Ciechanowicz, A

    2013-03-01

    The etiology of drug addiction, a central nervous system (CNS) disease, is not fully known. This complex problem is believed to be connected with concurrently affecting genetic, psychological and environmental factors. The development of addiction is connected with CNS reinforcement system and dopaminergic neurotransmission. Molecular processes are postulated to be of universal character and allow to presume a similar mechanism of dependence for both ethanol and other substances. Therefore, elements of dopaminergic transmission become excellent candidates for the examination of genetic influence on the development of addiction. A relationship between alcoholic disease and the presence of TaqIA1 and DRD2 alleles permits to initiate another investigation of gene-coding DRD2 dopamine receptor. The latest results indicate the importance of brain-derived neurotrophic factor (BDNF) in the regulation of dopaminergic route. The purpose of this research was to reveal the relationship between the Val66Met BDNF gene polymorphism and dependence of psychoactive agent. The examinations were performed with the Local Research Ethics Committee approval and patient's consent. The study group consisted of 100 patients (88 men and 12 women) aged 18-52 years, qualified for research program according to the International Classification of Diseases, Tenth Revision (ICD-10) requirements, medical examination and detailed questionnaire.

  4. Adenosine receptor neurobiology: overview.

    Science.gov (United States)

    Chen, Jiang-Fan; Lee, Chien-fei; Chern, Yijuang

    2014-01-01

    Adenosine is a naturally occurring nucleoside that is distributed ubiquitously throughout the body as a metabolic intermediary. In the brain, adenosine functions as an important upstream neuromodulator of a broad spectrum of neurotransmitters, receptors, and signaling pathways. By acting through four G-protein-coupled receptors, adenosine contributes critically to homeostasis and neuromodulatory control of a variety of normal and abnormal brain functions, ranging from synaptic plasticity, to cognition, to sleep, to motor activity to neuroinflammation, and cell death. This review begun with an overview of the gene and genome structure and the expression pattern of adenosine receptors (ARs). We feature several new developments over the past decade in our understanding of AR functions in the brain, with special focus on the identification and characterization of canonical and noncanonical signaling pathways of ARs. We provide an update on functional insights from complementary genetic-knockout and pharmacological studies on the AR control of various brain functions. We also highlight several novel and recent developments of AR neurobiology, including (i) recent breakthrough in high resolution of three-dimension structure of adenosine A2A receptors (A2ARs) in several functional status, (ii) receptor-receptor heterodimerization, (iii) AR function in glial cells, and (iv) the druggability of AR. We concluded the review with the contention that these new developments extend and strengthen the support for A1 and A2ARs in brain as therapeutic targets for neurologic and psychiatric diseases.

  5. Imidazoline receptors ligands

    Directory of Open Access Journals (Sweden)

    Agbaba Danica

    2012-01-01

    Full Text Available Extensive biochemical and pharmacological studies have determined three different subtypes of imidazoline receptors: I1-imidazoline receptors (I1-IR involved in central inhibition of sympathicus that produce hypotensive effect; I2-imidazoline receptors (I2-IR modulate monoamine oxidase B activity (MAO-B; I3-imidazoline receptors (I3-IR regulate insulin secretion from pancreatic β-cells. Therefore, the I1/I2/I3 imidazoline receptors are selected as new, interesting targets for drug design and discovery. Novel selective I1/I2/I3 agonists and antagonists have been recently developed. In the present review, we provide a brief update to the field of imidazoline research, highlighting some of the chemical diversity and progress made in the 2D-QSAR, 3D-QSAR and quantitative pharmacophore development studies of I1-IR and I2-IR imidazoline receptor ligands. Theoretical studies of I3-IR ligands are not yet performed because of insufficient number of synthesized I3-IR ligands.

  6. Noribogaine is a G-protein biased κ-opioid receptor agonist.

    Science.gov (United States)

    Maillet, Emeline L; Milon, Nicolas; Heghinian, Mari D; Fishback, James; Schürer, Stephan C; Garamszegi, Nandor; Mash, Deborah C

    2015-12-01

    Noribogaine is the long-lived human metabolite of the anti-addictive substance ibogaine. Noribogaine efficaciously reaches the brain with concentrations up to 20 μM after acute therapeutic dose of 40 mg/kg ibogaine in animals. Noribogaine displays atypical opioid-like components in vivo, anti-addictive effects and potent modulatory properties of the tolerance to opiates for which the mode of action remained uncharacterized thus far. Our binding experiments and computational simulations indicate that noribogaine may bind to the orthosteric morphinan binding site of the opioid receptors. Functional activities of noribogaine at G-protein and non G-protein pathways of the mu and kappa opioid receptors were characterized. Noribogaine was a weak mu antagonist with a functional inhibition constants (Ke) of 20 μM at the G-protein and β-arrestin signaling pathways. Conversely, noribogaine was a G-protein biased kappa agonist 75% as efficacious as dynorphin A at stimulating GDP-GTP exchange (EC50=9 μM) but only 12% as efficacious at recruiting β-arrestin, which could contribute to the lack of dysphoric effects of noribogaine. In turn, noribogaine functionally inhibited dynorphin-induced kappa β-arrestin recruitment and was more potent than its G-protein agonistic activity with an IC50 of 1 μM. This biased agonist/antagonist pharmacology is unique to noribogaine in comparison to various other ligands including ibogaine, 18-MC, nalmefene, and 6'-GNTI. We predict noribogaine to promote certain analgesic effects as well as anti-addictive effects at effective concentrations>1 μM in the brain. Because elevated levels of dynorphins are commonly observed and correlated with anxiety, dysphoric effects, and decreased dopaminergic tone, a therapeutically relevant functional inhibition bias to endogenously released dynorphins by noribogaine might be worthy of consideration for treating anxiety and substance related disorders.

  7. Blockade of dorsal hippocampal orexin-1 receptors impaired morphine-induced state-dependent learning.

    Science.gov (United States)

    Farahmandfar, Maryam; Kadivar, Mehdi; Rastipisheh, Sareh

    2016-12-01

    Behavioral abnormalities associated with opiate addiction include memory and learning deficits, which are the result of some alterations in the neuromodulatory systems. Recently, orexin has shown to influence drug addiction neural circuitry, specifically in mediating reward-related perception and memory. To explore the possible interaction of orexinergic and opioidergic system on modulation of learning and memory, we have investigated the effects of intra-dorsal hippocampal (intra-CA1) administration of orexin-1 receptor agonist and the competitive orexin-1 antagonist, SB-334867, on morphine-induced memory impairment by using step-down passive avoidance task in mice. Pre-training injection of morphine (5mg/kg, i.p.) impaired memory, which was restored when 24h later the same dose of the drug was administered. Pre-test administration of orexin-1 (0.5, 5 and 50pmol, intra-CA1) had not a significant effect on the retention latency compared to the saline-treated animals, but it restored the memory impairment induced by pre-training morphine (5mg/kg, i.p.). Pre-test administration of SB-334867 (10, 20 and 40nmol, intra-CA1) by itself decreased the retention latencies of passive avoidance task. Co-administration of orexin-1 (0.5, 5 and 50pmol, intra-CA1) and morphine (1mg/kg, i.p.) on the test day induced morphine state-dependent memory. Conversely, pre-test injection of SB-334867 (10, 20 and 40nmol, intra-CA1) inhibited the orexin-1-induced potentiation of morphine state-dependent learning on the test day. It is concluded that dorsal hippocampal orexin-1 receptors may be involved, at least in part, in morphine state-dependent learning in mice.

  8. General pharmacological properties of a new non-opiate antitussive: zipeprol (3024 CERM). I. Action on respiratory function and acute toxicity.

    Science.gov (United States)

    Rispat, G; Burgi, H; Cosnier, D; Duchêne-Marullaz, P; Streichenberger, G

    1976-04-01

    1-(2-Methoxy-2-phenyl)-ethyl-4-(2-hydroxy-3-methoxy-3-phenyl)-propyl-iperazine-dihydrochloride (zipeprol, Respilene) is a substance of non-phenanthrenic chemical structure. In the cat, it antagonised cough induced by stimulation of the superior laryngeal nerve or by direct mechanical excitation of the sensitive tracheo-bronchial receptors. The efficacy of zipeprol after enteral administration made it possible both to establish good intestinal absorption and to rank it favourably in relation to several major antitussive reference products; codeine, codethyline, dextromethorphan, diphenhydramine and pentoxyverine. The activity of zipeprol was superior or equal to that of all these substances, excdept codeine. The antitussive properties appeared to be due to a central action. Other properties have been demonstrated which suggest at least a supplementary mechanism in the inhibition of cough, in addition to the central action. These consisted of slight antihistamine and anticholinergic properties, marked local-anesthetic potency and bronchospasmolytic activity. This latter property was demonstrated by the inhibition of histamine and serotonin induced bronchospasm in the guinea-pig. In vitro, using human sputum, zipeprol had a mucolytic action, shown by a decrease in sputum vis viscosity and lysis of DNA and AMPS fibrils. In the dog, at high doses, zipeprol unlike codeine, did not inhibit central stimulation of respiration by hypercapnia, in addition no modification of ventilatory dynamics or blood gases was seen. On the basis of these results, zipeprol can be considered as possessing no respiratory depressant effect even in the upper ranges of its antitussive doses.

  9. Positron-emissionstomografisk kortlaegning af den levende menneskehjernes receptorer

    DEFF Research Database (Denmark)

    Gjedde, A

    2001-01-01

    tracers are used in diseases of the basal ganglia, whereas serotonin, benzodiazepine, and opiate tracers are used in lesions of the cerebral cortex. PET has revealed loss of dopaminergic terminals and dopamine synthetic capacity in Parkinson's disease, MPTP intoxication, and Lesch-Nyhan's syndrome...

  10. Ionotropic crustacean olfactory receptors.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Corey

    Full Text Available The nature of the olfactory receptor in crustaceans, a major group of arthropods, has remained elusive. We report that spiny lobsters, Panulirus argus, express ionotropic receptors (IRs, the insect chemosensory variants of ionotropic glutamate receptors. Unlike insects IRs, which are expressed in a specific subset of olfactory cells, two lobster IR subunits are expressed in most, if not all, lobster olfactory receptor neurons (ORNs, as confirmed by antibody labeling and in situ hybridization. Ligand-specific ORN responses visualized by calcium imaging are consistent with a restricted expression pattern found for other potential subunits, suggesting that cell-specific expression of uncommon IR subunits determines the ligand sensitivity of individual cells. IRs are the only type of olfactory receptor that we have detected in spiny lobster olfactory tissue, suggesting that they likely mediate olfactory signaling. Given long-standing evidence for G protein-mediated signaling in activation of lobster ORNs, this finding raises the interesting specter that IRs act in concert with second messenger-mediated signaling.

  11. Simultaneous detection and quantification of amphetamines, diazepam and its metabolites, cocaine and its metabolites, and opiates in hair by LC-ESI-MS-MS using a single extraction method.

    Science.gov (United States)

    Miller, Eleanor I; Wylie, Fiona M; Oliver, John S

    2008-09-01

    A liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous identification and quantification of amphetamines, diazepam and its metabolites, cocaine and its metabolites, and opiates from hair using a single extraction method. As part of the method development, Gemini C18, Synergi Hydro RP, and Zorbax Stablebond-Phenyl LC columns were tested with three different mobile phases. Analyte recovery and limit of detection were evaluated for two different solid-phase extraction methods that used Bond Elut Certify and Clean Screen cartridges. Phosphate buffer (pH 5.0) was chosen as the optimum hair incubation medium because of the high stability of cocaine and 6-monoacetylmorphine using this method and faster sample preparation. The optimized method was fully validated. Linearity was established over the concentration range 0.2-10 ng/mg hair, and the correlation coefficients were all greater than 0.99. Total extraction recoveries were greater than 76%, detection limits were between 0.02 and 0.09 ng/mg, and the intra- and interday imprecisions were generally less than 20% in spiked hair. The intra- and interbatch imprecision of the method for a pooled authentic hair sample ranged from 1.4 to 23.4% relative standard deviation (RSD) and 8.3 to 25.4% RSD, respectively, for representative analytes from the different drug groups. The percent matrix effect ranged from 63.5 to 135.6%, with most analytes demonstrating ion suppression. Sixteen postmortem samples collected from suspected drug-related deaths were analyzed for the 17 drugs of abuse and metabolites included in the method. The method was sufficiently sensitive and specific for the analysis of drugs and metabolites in postmortem hair samples. There is scope for the inclusion of other target drugs and metabolites in the method.

  12. Development and validation of two LC-MS/MS methods for the detection and quantification of amphetamines, designer amphetamines, benzoylecgonine, benzodiazepines, opiates, and opioids in urine using turbulent flow chromatography.

    Science.gov (United States)

    Schaefer, Nadine; Peters, Benjamin; Schmidt, Peter; Ewald, Andreas H

    2013-01-01

    In the context of driving ability diagnostics in Germany, administrative cutoffs for various drugs and pharmaceuticals in urine have been established. Two liquid chromatography-tandem mass spectrometry methods for simultaneous detection and quantification of amphetamines, designer amphetamines, benzoylecgonine, benzodiazepines, opiates, and opioids in urine were developed and validated. A 500-μL aliquot of urine was diluted and fortified with an internal standard solution. After enzymatic cleavage, online extraction was performed by an ion-exchange/reversed-phase turbulent flow column. Separation was achieved by using a reversed-phase column and gradient elution. For detection, a Thermo Fisher TSQ Quantum Ultra Accurate Mass tandem mass spectrometer with positive electrospray ionization was used, and the analytes were measured in multiple-reaction monitoring mode detecting two transitions per precursor ion. The total run time for both methods was about 15 min. Validation was performed according to the guidelines of the Society of Toxicological and Forensic Chemistry. The results of matrix effect determination were between 78% and 116%. The limits of detection and quantification for all drugs, except zopiclone, were less than 10 ng/mL and less than 25 ng/mL, respectively. Calibration curves ranged from 25 to 200 ng/mL for amphetamines, designer amphetamines, and benzoylecgonine, from 25 to 250 ng/mL for benzodiazepines, from 12.5 to 100 ng/mL for morphine, codeine, and dihydrocodeine, and from 5 to 50 ng/mL for buprenorphine and norbuprenorphine. Intraday and interday precision values were lower than 15%, and bias values within ± 15% were achieved. Turbulent flow chromatography needs no laborious sample preparation, so the workup is less time-consuming compared with gas chromatography-mass spectrometry methods. The methods are suitable for quantification of multiple analytes at the cutoff concentrations required for driving ability diagnostics in Germany.

  13. Monitoring Intravenous Abuse of Methadone or Buprenorphine in Opiate Maintenance Treatment (OMT): A Simple and Fast LC-MS-MS Method for the Detection of Disaccharides in Urine Samples.

    Science.gov (United States)

    Jungen, Hilke; Andresen-Streichert, Hilke; Müller, Alexander; Iwersen-Bergmann, Stefanie

    2017-01-01

    The detection of disaccharides in urine is under investigation to act as a marker for intravenous abuse of disaccharide formulations, like liquid methadone with syrup (sucrose), methadone tablets (lactose and sucrose), or buprenorphine tablets (lactose). As the detection time in urine has not yet been investigated and a routine method for detecting disaccharides is still lacking, a study was performed to estimate the window of detection in urine after intravenous consumption of disaccharides. Furthermore, an analytical LC-MSMS method for the quantification of sucrose and lactose in urine was validated. The method was applied to urine samples of intravenous substitute consumers, with urine being sampled before intravenous use of substitutes and approximately 30 minutes later. Twenty users provided information regarding their most recent prior intravenous consumption. Disaccharides were detectable in all 20 urine samples about 30 minutes after consumption. A cut off for both disaccharides of 40mg/L was used. Based on these conditions 81% of the persons who consumed in a time frame of 24 hours ago showed positive results for disaccharides. The study showed that the validated LC-MSMS method with an easy and fast workup is usable for daily routine in the laboratory. It might be helpful for methadone and buprenorphine prescribing physicians to check whether the opiate maintenance treatment patient takes his or her substitution medicines orally as intended, or continues with intravenous misuse by injecting substitution medicines instead of heroin. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Sex risk behavior among adolescent and young adult children of opiate addicts: outcomes from the focus on families prevention trial and an examination of childhood and concurrent predictors of sex risk behavior.

    Science.gov (United States)

    Skinner, Martie L; Fleming, Charles B; Haggerty, Kevin P; Catalano, Richard F

    2014-02-01

    This study reports on rates and predictors of sex risk behavior among a sample of adolescent and young adult children of parents enrolled in methadone treatment for opiate addiction. Data are from 151 participants (80 males, 71 females) in the Focus on Families (FOF) project, a randomized trial of a family intervention and a study of the development of at-risk children. The study participants are children of parents enrolled in methadone treatment between 1990 and 1993. Participants were interviewed in 2005 when they ranged in age from 15 to 29 years. In the year prior to the follow-up, 79% of the males and 83% of females were sexually active, 26% of males and 10% of females had more than one partner in the prior year, and 34% of males and 24% of females reported having sex outside of a committed relationship. Twenty-four percent of males and 17% of females met criteria for high-risk sexual behavior, reporting casual or multiple partners in the prior year and inconsistent condom use. Participants in the intervention and control conditions did not differ significantly in terms of any measure of sex risk behavior examined. None of the measures of parent behavior and family processes derived from data at baseline of the FOF study predicted whether participants engaged in high-risk sex. Among measures derived from data collected at long-term follow-up, however, having ever met criteria for substance abuse or dependence predicted greater likelihood of high-risk sexual behavior, and being married or being in a romantic relationship was associated with lower likelihood of high-risk sexual behavior. The findings point to the important role of committed relationships in regulating sex risk behavior among this population, as well as heightened levels of sex risk behavior associated with substance abuse or dependence.

  15. NCBI nr-aa BLAST: CBRC-PVAM-01-0526 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PVAM-01-0526 ref|NP_000904.1| opiate receptor-like 1 [Homo sapiens] ref|NP_872588.1| opiate...gb|AAA84913.1| orphan opioid receptor [Homo sapiens] gb|AAH38433.1| OPRL1 protein [Homo sapiens] gb|AAP23195.1| opiate... receptor-like 1 [Homo sapiens] emb|CAG46858.1| OPRL1 [Homo sapiens] emb|CAD11904.2| opiate recept...or-like 1 [Homo sapiens] emb|CAC17003.2| opiate receptor-like 1 [Homo sapiens] gb|ABM84132.1| opiate... receptor-like 1 [synthetic construct] gb|ABM84133.1| opiate receptor-like 1 [synthetic c

  16. NCBI nr-aa BLAST: CBRC-MLUC-01-0678 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MLUC-01-0678 ref|NP_000904.1| opiate receptor-like 1 [Homo sapiens] ref|NP_872588.1| opiate...gb|AAA84913.1| orphan opioid receptor [Homo sapiens] gb|AAH38433.1| OPRL1 protein [Homo sapiens] gb|AAP23195.1| opiate... receptor-like 1 [Homo sapiens] emb|CAG46858.1| OPRL1 [Homo sapiens] emb|CAD11904.2| opiate recept...or-like 1 [Homo sapiens] emb|CAC17003.2| opiate receptor-like 1 [Homo sapiens] gb|ABM84132.1| opiate... receptor-like 1 [synthetic construct] gb|ABM84133.1| opiate receptor-like 1 [synthetic c

  17. NCBI nr-aa BLAST: CBRC-MEUG-01-1362 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MEUG-01-1362 ref|NP_000904.1| opiate receptor-like 1 [Homo sapiens] ref|NP_872588.1| opiate...gb|AAA84913.1| orphan opioid receptor [Homo sapiens] gb|AAH38433.1| OPRL1 protein [Homo sapiens] gb|AAP23195.1| opiate... receptor-like 1 [Homo sapiens] emb|CAG46858.1| OPRL1 [Homo sapiens] emb|CAD11904.2| opiate recept...or-like 1 [Homo sapiens] emb|CAC17003.2| opiate receptor-like 1 [Homo sapiens] gb|ABM84132.1| opiate... receptor-like 1 [synthetic construct] gb|ABM84133.1| opiate receptor-like 1 [synthetic c

  18. NCBI nr-aa BLAST: CBRC-PHAM-01-0451 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PHAM-01-0451 ref|NP_000904.1| opiate receptor-like 1 [Homo sapiens] ref|NP_872588.1| opiate...gb|AAA84913.1| orphan opioid receptor [Homo sapiens] gb|AAH38433.1| OPRL1 protein [Homo sapiens] gb|AAP23195.1| opiate... receptor-like 1 [Homo sapiens] emb|CAG46858.1| OPRL1 [Homo sapiens] emb|CAD11904.2| opiate recept...or-like 1 [Homo sapiens] emb|CAC17003.2| opiate receptor-like 1 [Homo sapiens] gb|ABM84132.1| opiate... receptor-like 1 [synthetic construct] gb|ABM84133.1| opiate receptor-like 1 [synthetic c

  19. NCBI nr-aa BLAST: CBRC-MMUR-01-0596 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MMUR-01-0596 ref|NP_000904.1| opiate receptor-like 1 [Homo sapiens] ref|NP_872588.1| opiate...gb|AAA84913.1| orphan opioid receptor [Homo sapiens] gb|AAH38433.1| OPRL1 protein [Homo sapiens] gb|AAP23195.1| opiate... receptor-like 1 [Homo sapiens] emb|CAG46858.1| OPRL1 [Homo sapiens] emb|CAD11904.2| opiate recept...or-like 1 [Homo sapiens] emb|CAC17003.2| opiate receptor-like 1 [Homo sapiens] gb|ABM84132.1| opiate... receptor-like 1 [synthetic construct] gb|ABM84133.1| opiate receptor-like 1 [synthetic c

  20. NCBI nr-aa BLAST: CBRC-MDOM-01-0382 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MDOM-01-0382 ref|NP_000904.1| opiate receptor-like 1 [Homo sapiens] ref|NP_872588.1| opiate...gb|AAA84913.1| orphan opioid receptor [Homo sapiens] gb|AAH38433.1| OPRL1 protein [Homo sapiens] gb|AAP23195.1| opiate... receptor-like 1 [Homo sapiens] emb|CAG46858.1| OPRL1 [Homo sapiens] emb|CAD11904.2| opiate recept...or-like 1 [Homo sapiens] emb|CAC17003.2| opiate receptor-like 1 [Homo sapiens] gb|ABM84132.1| opiate... receptor-like 1 [synthetic construct] gb|ABM84133.1| opiate receptor-like 1 [synthetic c

  1. Presynaptic P2 receptors?

    Science.gov (United States)

    Stone, T W; O'Kane, E M; Nikbakht, M R; Ross, F M

    2000-07-01

    Although the emphasis in ATP research has been on postjunctional receptors, there is also evidence for presynaptic receptors regulating transmitter release in the autonomic nervous system. Recent work has attempted to identify similar mechanisms in the central nervous system. Some of the existing results can be explained by the metabolism of nucleotides to adenosine or adenosine 5'-monophosphate (AMP). However, studies of presynaptic effects using sensitive electrophysiological tests such as paired-pulse interactions indicate that nucleotides can act at presynaptic sites, but that their effects may be mediated by a release of adenosine. Results are also described which indicate that, under some conditions, nucleotides can mediate phenomena such as long-term potentiation, which probably involves a significant presynaptic element. In part these effects may involve a nucleotide-induced release of adenosine and the simultaneous activation of P1 and P2 receptors.

  2. Human presynaptic receptors.

    Science.gov (United States)

    Schlicker, Eberhard; Feuerstein, Thomas

    2017-04-01

    Presynaptic receptors are sites at which transmitters, locally formed mediators or hormones inhibit or facilitate the release of a given transmitter from its axon terminals. The interest in the identification of presynaptic receptors has faded in recent years and it may therefore be justified to give an overview of their occurrence in the autonomic and central nervous system; this review will focus on presynaptic receptors in human tissues. Autoreceptors are presynaptic receptors at which a given transmitter restrains its further release, though in some instances may also increase its release. Inhibitory autoreceptors represent a typical example of a negative feedback; they are tonically activated by the respective endogenous transmitter and/or are constitutively active. Autoreceptors also play a role under pathophysiological conditions, e.g. by limiting the massive noradrenaline release occurring during congestive heart failure. They can be used for therapeutic purposes; e.g., the α2-adrenoceptor antagonist mirtazapine is used as an antidepressant and the inverse histamine H3 receptor agonist pitolisant has been marketed as a new drug for the treatment of narcolepsy in 2016. Heteroreceptors are presynaptic receptors at which transmitters from adjacent neurons, locally formed mediators (e.g. endocannabinoids) or hormones (e.g. adrenaline) can inhibit or facilitate transmitter release; they may be subject to an endogenous tone. The constipating effect of the sympathetic nervous system or of the antihypertensive drug clonidine is related to the activation of inhibitory α2-adrenoceptors on postganglionic parasympathetic neurons. Part of the stimulating effect of adrenaline on the sympathetic nervous system during stress is related to its facilitatory effect on noradrenaline release via β2-adrenoceptors.

  3. Biomimetic Receptors and Sensors

    Directory of Open Access Journals (Sweden)

    Franz L. Dickert

    2014-11-01

    Full Text Available In biomimetics, living systems are imitated to develop receptors for ions, molecules and bioparticles. The most pertinent idea is self-organization in analogy to evolution in nature, which created the key-lock principle. Today, modern science has been developing host-guest chemistry, a strategy of supramolecular chemistry for designing interactions of analytes with synthetic receptors. This can be realized, e.g., by self-assembled monolayers (SAMs or molecular imprinting. The strategies are used for solid phase extraction (SPE, but preferably in developing recognition layers of chemical sensors.

  4. Beyond the Receptor

    Institute of Scientific and Technical Information of China (English)

    Russell Jones

    2008-01-01

    @@ Had this Special Issue on plant hormones been published 5 years ago,it is likely that details about biosynthetic pathways would have taken center stage.As articles in this issue show,however,the field of plant hormone research has progressed rapidly and is now moving beyond the search for receptors.Progress in research on the mechanism of action of plant hormones has been rapid;receptors for the main classes of hormones have been identified;and the search is on for players downstream in signal-transduction chains.

  5. Assays for calcitonin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Teitelbaum, A.P.; Nissenson, R.A.; Arnaud, C.D.

    1985-01-01

    The assays for calcitonin receptors described focus on their use in the study of the well-established target organs for calcitonin, bone and kidney. The radioligand used in virtually all calcitonin binding studies is /sup 125/I-labelled salmon calcitonin. The lack of methionine residues in this peptide permits the use of chloramine-T for the iodination reaction. Binding assays are described for intact bone, skeletal plasma membranes, renal plasma membranes, and primary kidney cell cultures of rats. Studies on calcitonin metabolism in laboratory animals and regulation of calcitonin receptors are reviewed.

  6. Chemokine Receptors and Transplantation

    Institute of Scientific and Technical Information of China (English)

    Jinquan Tan; Gang Zhou

    2005-01-01

    A complex process including both the innate and acquired immune responses results in allograft rejection. Some chemokine receptors and their ligands play essential roles not only for leukocyte migration into the graft but also in facilitating dendritic and T cell trafficking between lymph nodes and the transplant in the early and late stage of the allogeneic response. This review focuses on the impact of these chemoattractant proteins on transplant outcome and novel diagnostic and therapeutic approaches for antirejection therapy based on targeting of chemokine receptors and/or their ligands. Cellular & Molecular Immunology.

  7. Angiotensin type 2 receptor (AT2R) and receptor Mas

    DEFF Research Database (Denmark)

    Villela, Daniel; Leonhardt, Julia; Patel, Neal

    2015-01-01

    The angiotensin type 2 receptor (AT2R) and the receptor Mas are components of the protective arms of the renin-angiotensin system (RAS), i.e. they both mediate tissue protective and regenerative actions. The spectrum of actions of these two receptors and their signalling mechanisms display striking...

  8. 吗啡耐受过程中δ阿片受体对μ阿片受体功能的调节作用%Role of the delta -opioid receptor in the regulation of mu -opioid receptor function during morphine tolerance

    Institute of Scientific and Technical Information of China (English)

    苏林; 王国林

    2010-01-01

    Morphine tolerance involves numerous and complex mechanisms. The heterodimerization of mu and delta opioid receptors put forward recently is one of the important mechanisms which cause the development of opiate tolerance. Once transported to the membrane of neural cells, delta opioid receptors (DOR) combine with mu opioid receptors (MOR) to form MOR-DOR heterodimers,leading to the formation of new signaling pathway. This novel mechanism plays the critical role of DOR in the development of morphine tolerance. This review summarizes the regulation of DOR on MOR function during morphine tolerance in light of the recent findings about the regulation of DOR membrane transport and the new complex: MOR-DOR heterodimer.%吗啡耐受涉及繁多而复杂的机制,μ阿片受体(mu opioid receptors,MOR)和δ阿片受体(delta opioid receptors,DOR)单体异体二聚化就是最近提出的促成阿片耐受发展的重要机制之一.DOR被转运到细胞膜表面后可以与MOR结合形成MOR-DOR二聚物并产生新的信号转导途径.这一机制表明DOR在吗啡耐受发展中所起的重要作用.现从DOR质膜转运的调节以及转运后DOR和MOR形成的新的受体复合物阐述吗啡耐受过程中DOR对MOR功能的调节作用.

  9. Characterization of melanocortin receptors.

    Science.gov (United States)

    Goetz, Aaron S; Ignar, Diane M

    2003-11-01

    This unit describes a Scintillation Proximity Assay (SPA) for the measurement of ligand binding to melanocortin receptors (MCRs) using membranes prepared from cell lines stably expressing recombinant MCRs. It provides a facile method for determining the affinity of compounds at MC1R, MC3R, MC4R, or MC5R.

  10. P2-purinerge receptorer

    DEFF Research Database (Denmark)

    Solgaard, Marie; Jørgensen, Niklas Rye

    2005-01-01

    and by osteoclasts, and agonist binding affects cell proliferation, differentiation, activity and apoptosis. With increasing knowledge of the function and role of these receptors in bone biology, they will undoubtedly be a future target for the design of new drugs which can be used for treatment of metabolic bone...

  11. Meeting report: nuclear receptors

    DEFF Research Database (Denmark)

    Tuckermann, Jan; Bourguet, William; Mandrup, Susanne

    2010-01-01

    The biannual European Molecular Biology Organization (EMBO) conference on nuclear receptors was organized by Beatrice Desvergne and Laszlo Nagy and took place in Cavtat near Dubrovnik on the Adriatic coast of Croatia September 25-29, 2009. The meeting brought together researchers from all over...

  12. Glutamate receptor ligands

    DEFF Research Database (Denmark)

    Guldbrandt, Mette; Johansen, Tommy N; Frydenvang, Karla Andrea;

    2002-01-01

    Homologation and substitution on the carbon backbone of (S)-glutamic acid [(S)-Glu, 1], as well as absolute stereochemistry, are structural parameters of key importance for the pharmacological profile of (S)-Glu receptor ligands. We describe a series of methyl-substituted 2-aminoadipic acid (AA......-ray crystallographic analyses, chemical correlation, and CD spectral analyses. The effects of the individual stereoisomers at ionotropic and metabotropic (S)-Glu receptors (iGluRs and mGluRs) were characterized. Compounds with S-configuration at the alpha-carbon generally showed mGluR2 agonist activity of similar...... limited effect on pharmacology. Structure-activity relationships at iGluRs in the rat cortical wedge preparation showed a complex pattern, some compounds being NMDA receptor agonists [e.g., EC(50) =110 microM for (2S,5RS)-5-methyl-AA (6a,b)] and some compounds showing NMDA receptor antagonist effects [e...

  13. Ginkgolides and glycine receptors

    DEFF Research Database (Denmark)

    Jaracz, Stanislav; Nakanishi, Koji; Jensen, Anders A.

    2004-01-01

    Ginkgolides from the Ginkgo biloba tree are diterpenes with a cage structure consisting of six five-membered rings and a unique tBu group. They exert a variety of biological properties. In addition to being antagonists of the platelet activating factor receptor (PAFR), it has recently been shown...

  14. Androgen receptor mutations

    NARCIS (Netherlands)

    A.O. Brinkmann (Albert); G.W. Jenster (Guido); C. Ris-Stalpers (Carolyn); J.A.G.M. van der Korput (J. A G M); H.T. Brüggenwirth (Hennie); A.L.M. Boehmer (Annemie); J. Trapman (Jan)

    1995-01-01

    textabstractMale sexual differentiation and development proceed under direct control of androgens. Androgen action is mediated by the intracellular androgen receptor, which belongs to the superfamily of ligand-dependent transcription factors. At least three pathological situations are associated wit

  15. Metformin and insulin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific /sup 125/I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific /sup 125/I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded.

  16. Levamisole receptors: a second awakening

    Science.gov (United States)

    Martin, Richard J.; Robertson, Alan P.; Buxton, Samuel K.; Beech, Robin N.; Charvet, Claude L.; Neveu, Cedric

    2012-01-01

    Levamisole and pyrantel are old (1965) but useful anthelmintics that selectively activate nematode acetylcholine ion-channel receptors; they are used to treat roundworm infections in humans and animals. Interest in their actions has surged, giving rise to new knowledge and technical advances, including an ability to reconstitute receptors that reveal more details of modes of action/resistance. We now know that the receptors are plastic and may form diverse species-dependent subtypes of receptor with different sensitivities to individual cholinergic anthelmintics. Understanding the biology of the levamisole receptors is expected to inform other studies on anthelmintics (ivermectin and emodepside) that act on ion-channels. PMID:22607692

  17. Histamine H3-receptor isoforms.

    Science.gov (United States)

    Bakker, R A

    2004-10-01

    Increasing evidence supports a role for HA as a neurotransmitter and neuromodulator in various brain functions, including emotion, cognition, and feeding. The recent cloning of the histamine H3 receptor allowed for the subsequent cloning of a variety of H3 receptor isoforms from different species as well as the H4 receptor. As a result a wide variety of H3-receptor isoforms are now known that display differential brain expression patterns and signalling properties. These recent discoveries are discussed in view of the growing interest of the H3 receptor as a target for the development of potential therapeutics.

  18. Virally encoded 7TM receptors

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Waldhoer, M; Lüttichau, H R

    2001-01-01

    A number of herpes- and poxviruses encode 7TM G-protein coupled receptors most of which clearly are derived from their host chemokine system as well as induce high expression of certain 7TM receptors in the infected cells. The receptors appear to be exploited by the virus for either immune evasion...... in various parts of the viral life cyclus. Most of the receptors encoded by human pathogenic virus are still orphan receptors, i.e. the endogenous ligand is unknown. In the few cases where it has been possible to characterize these receptors pharmacologically, they have been found to bind a broad spectrum...... expression of this single gene in certain lymphocyte cell lineages leads to the development of lesions which are remarkably similar to Kaposi's sarcoma, a human herpesvirus 8 associated disease. Thus, this and other virally encoded 7TM receptors appear to be attractive future drug targets....

  19. Receptor tyrosine kinases in carcinogenesis.

    Science.gov (United States)

    Zhang, Xiao-Ying; Zhang, Pei-Ying

    2016-11-01

    Receptor tyrosine kinases (RTKs) are cell surface glycoproteins with enzymatic activity involved in the regulation of various important functions. In all-important physiological functions including differentiation, cell-cell interactions, survival, proliferation, metabolism, migration and signaling these receptors are the key players of regulation. Additionally, mutations of RTKs or their overexpression have been described in many human cancers and are being explored as a novel avenue for a new therapeutic approach. Some of the deregulated RTKs observed to be significantly affected in cancers included vascular endothelial growth factor receptor, epidermal growth factor receptor, fibroblast growth factor receptor, RTK-like orphan receptor 1 (ROR1) and the platelet-derived growth factor receptor. These deregulated RTKs offer attractive possibilities for the new anticancer therapeutic approach involving specific targeting by monoclonal antibodies as well as kinase. The present review aimed to highlight recent perspectives of RTK ROR1 in cancer.

  20. TSH RECEPTOR AUTOANTIBODIES

    Science.gov (United States)

    Michalek, Krzysztof; Morshed, Syed A.; Latif, Rauf; Davies, Terry F.

    2009-01-01

    Thyrotropin receptor autoantibodies (TSHR-Abs) of the stimulating variety are the hallmark of Graves’ disease. The presence of immune defects leading to synthesis of TSHR-Abs causes hyperthyroidism and is associated with other extrathyroidal manifestations. Further characterization of these antibodies has now been made possible by the generation of monoclonal antibodies with this unique stimulating capacity as well as similar TSHR-Abs not associated with hyperthyroidism. Their present classification divides TSHR-Abs into stimulating, blocking (competing with TSH binding) and neutral (no signaling). Recent studies using monoclonal TSHR-Abs has revealed that stimulating and blocking antibodies bind to the receptor using mostly conformational epitopes, whilst neutral antibodies utilize exclusively linear peptides. Subtle differences in epitopes for stimulating and blocking antibodies account for the diversity of their biological actions. Recently non-classical signaling elicited by neutral antibodies has also been described, raising the need for a new classification of TSHR-Abs. PMID:19332151

  1. Ligand-Receptor Interactions

    CERN Document Server

    Bongrand, Pierre

    2008-01-01

    The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the ...

  2. 异病酚静脉全麻下复合氯胺酮或曲马多行纳屈酮快速阿片脱毒的效果比较%The comparison of effects of rapid opiate detoxification with ketamine complex and with tramadol and naltrexone under general anesthesia with propofol

    Institute of Scientific and Technical Information of China (English)

    黄位耀; 肖晓山; 刘瑛; 廖秀清; 周代伟; 戴航

    2002-01-01

    Objective To release the heroin addicts' sufferings,we made rapid opiate detoxification by injecting naloxine under the general anesthesia. Method 160 volunteers were divided at random into two groups:Group A were performed under the combined anesthesia with propofol, midazolam and ketamine,Group B were performed under the combined anesthesia with propofol with midazolam and tramadol. The vital signs were recorded and the withdrawal syndrome of the volunteers were assessed during the whole process.Result All of the withdrawal symptoms scores 24 hours after ROD in group B were lower than its pre-treatment;The symptoms of the thirst, sleeping disturbance,nausea and vomiting,skeletal muscular pains and anorexia scores in group A were also lower than its pre-treatment;and no too much difference between group A and group B.But tearing,anxiety and diarrhea scores in group A were almost the same as the pre-treatment and higher than group B.Both groups received of the naloxone treatment smoothly,and remained in the hospital for about 3 days. Conclusion The effect of rapid opiate detoxification of naltrexone with the ketamine or tramadol under anesthesia is obvious. The tramadol is better than others.

  3. The interleukin-4 receptor: signal transduction by a hematopoietin receptor.

    Science.gov (United States)

    Keegan, A D; Pierce, J H

    1994-02-01

    Over the last several years, the receptors for numerous cytokines have been molecularly characterized. Analysis of their amino acid sequences shows that some of these receptors bear certain motifs in their extracellular domains that define a family of receptors called the Hematopoietin receptor superfamily. Significant advances in characterizing the structure, function, and mechanisms of signal transduction have been made for several members of this family. The purpose of this review is to discuss the recent advances made for one of the family members, the interleukin (IL) 4 receptor. Other receptor systems have recently been reviewed elsewhere. The IL-4 receptor consists of, at the minimum, the cloned 140 kDa IL-4-binding chain with the potential for associating with other chains. The IL-4 receptor transduces its signal by activating a tyrosine kinase that phosphorylates cellular substrates, including the receptor itself, and the 170 kDa substrate called 4PS. Phosphorylated 4PS interacts with the SH2 domain of the enzyme PI-3'-kinase and increases its enzymatic activity. These early events in the IL-4 receptor initiated signaling pathway may trigger a series of signals that will ultimately lead to an IL-4 specific biologic outcome.

  4. Task-related functional connectivity of nucleus accumbens in opiate drug addicts during physical detoxification: a cue-elicited task fMRI study%生理脱毒期阿片类药物依赖者线索诱发作业下伏隔核功能连接的fMRI研究

    Institute of Scientific and Technical Information of China (English)

    韩易; 傅先明; 钱若兵; 林彬; 袁季; 魏祥品; 牛朝诗; 汪业汉

    2014-01-01

    目的 探讨生理脱毒期阿片类药物依赖者线索诱发作业下与伏隔核存在异常功能连接的脑区及其在戒断复吸中的作用.方法 生理脱毒期阿片类药物依赖组和健康对照组各18例,在观看与阿片类药物依赖线索相关视频时进行功能磁共振成像扫描,分别选取左、右侧伏隔核为感兴趣区进行功能连接分析,确定与双侧伏隔核存在功能连接的脑区.结果 与健康对照组相比,生理脱毒期阿片类药物依赖组的伏隔核与前额叶(46,29,-9)、岛叶(31,25,-7)、后扣带回(4,-59,19)、楔前叶(4,-63,22)、枕叶(6,71,16)、舌回(11,-37,-8)和距状回(3,-45,7)的功能连接明显高于健康对照组,而与丘脑(-8,-13,2)、前扣带回(-2,44,20)功能连接明显低于健康对照组(P<0.05).结论 生理脱毒期阿片类药物依赖者线索诱导下的伏隔核存在功能异常,这可能是其容易复吸的重要原因之一.%Objective To explore the brain areas which have abnormal functional connectivity with nucleus accumbens in opiate drug addicts during physical detoxification nsing a cue-elicited task-related functional magnetic resonance imaging (fMRI),and to find out the role of nucleus accumbens dysfunction in the relapse of opiate drug dependence during physical detoxification.Methods Eighteen participants of opiate drug addicts during physical detoxification,and eighteen healthy controls performed a cue-elicited craving task in a MRI scanner while signal data were collected.The left and right nucleus accumbens were selected as regions of interest (ROIs) respectively,and calculated the linear correlation between the nucleus accumbens and the entire brain to find out the functional connectivity of the nucleus accumbens.Results Compared with the controls,the functional connectivity between the nucleus accumbens and the prefrontal cortex (46,29,-9),insula(3 1,25,-7),posterior cingutate (4,-59,19),precuneus(4,-63,22),occipital lobe(6,71,16),lingual

  5. [Lipoprotein receptors. Old acquaintances and newcomers].

    Science.gov (United States)

    Ducobu, J

    1997-02-01

    Lipoprotein receptors are plasma membrane proteins of high affinity which interact with circulating lipoprotein particles. The well characterized LDL receptor continues to be analysed and some new findings on its intracellular mechanisms of action have emerged. New lipoprotein receptors have recently been described: the chylomicron remnant receptor or LDL-related protein (LRP), the lipolysis stimulated receptor (LSR), the very low density lipoprotein receptor (VLDLR), the HDL receptor (HDLR) and the scavenger receptor (SR). The molecular details of the receptors will facilitate the development of new therapeutic means to improve receptor-mediated clearance of lipoproteins.

  6. Ultrastructural relationship between the mu opioid receptor and its interacting protein, GPR177, in striatal neurons.

    Science.gov (United States)

    Reyes, Arith-Ruth S; Levenson, Robert; Berrettini, Wade; Van Bockstaele, Elisabeth J

    2010-10-28

    GPR177, the mammalian ortholog of Drosophila Wntless/Evi/Sprinter, was recently identified as a novel mu-opioid receptor (MOR) interacting protein. GPR177 is a trans-membrane protein pivotal to mediating the secretion of Wnt signaling proteins. Wnt proteins, in turn, are essential in regulating neuronal development, a phenomenon inhibited upon chronic exposure to MOR agonists such as morphine and heroin. We previously showed that GPR177 and MOR are co-localized in the mouse dorsolateral striatum; however, the nature of this interaction was not fully elucidated. Therefore, in the present study, we examined cellular substrates for interactions between GPR177 and MOR using a combined immunogold-silver and peroxidase detection approach in coronal sections in the dorsolateral segment of the striatum. Semi-quantitative analysis of the ultrastructural distribution of GPR177 and MOR in striatal somata and in dendritic processes showed that, of the somata and dendritic processes exhibiting GPR177, 32% contained MOR immunolabeling while for profiles exhibiting MOR, 37% also contained GPR177 immunoreactivity. GPR177-labeled particles were localized predominantly along both the plasma membrane and within the cytoplasm of MOR-labeled dendrites. Somata and dendritic processes that contained both GPR177 and MOR more often received symmetric (inhibitory-type) synapses from unlabeled axon terminals. To further define the phenotype of GPR177 and MOR-containing cellular profiles, triple immunofluorescence detection showed that GPR177 and MOR are localized in neurons containing the opioid peptide, enkephalin, within the dorsolateral striatum. The results provide an anatomical substrate for interactions between MOR and its interacting protein, GPR177, in striatal opioid-containing neurons that may underlie the morphological alterations produced in neurons by chronic opiate use.

  7. Brain neuronal CB2 cannabinoid receptors in drug abuse and depression: from mice to human subjects.

    Directory of Open Access Journals (Sweden)

    Emmanuel S Onaivi

    Full Text Available BACKGROUND: Addiction and major depression are mental health problems associated with stressful events in life with high relapse and reoccurrence even after treatment. Many laboratories were not able to detect the presence of cannabinoid CB2 receptors (CB2-Rs in healthy brains, but there has been demonstration of CB2-R expression in rat microglial cells and other brain associated cells during inflammation. Therefore, neuronal expression of CB2-Rs had been ambiguous and controversial and its role in depression and substance abuse is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study we tested the hypothesis that genetic variants of CB2 gene might be associated with depression in a human population and that alteration in CB2 gene expression may be involved in the effects of abused substances including opiates, cocaine and ethanol in rodents. Here we demonstrate that a high incidence of (Q63R but not (H316Y polymorphism in the CB2 gene was found in Japanese depressed subjects. CB2-Rs and their gene transcripts are expressed in the brains of naïve mice and are modulated following exposure to stressors and administration of abused drugs. Mice that developed alcohol preference had reduced CB2 gene expression and chronic treatment with JWH015 a putative CB2-R agonist, enhanced alcohol consumption in stressed but not in control mice. The direct intracerebroventricular microinjection of CB2 anti-sense oligonucleotide into the mouse brain reduced mouse aversions in the plus-maze test, indicating the functional presence of CB2-Rs in the brain that modifies behavior. We report for the using electron microscopy the sub cellular localization of CB2-Rs that are mainly on post-synaptic elements in rodent brain. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the functional expression of CB2-Rs in brain that may provide novel targets for the effects of cannabinoids in depression and substance abuse disorders beyond neuro-immunocannabinoid activity.

  8. Similarity of Bovine Rotavirus Receptor and Human Rotavirus Receptor

    Institute of Scientific and Technical Information of China (English)

    苏琦华; 訾自强; 潘菊芬; 徐燕

    2004-01-01

    The monoclonal antibody against bovine rotavirus (BRV) receptor (BRV-R-mAb) was used to explore the similarity between the receptors of BRV and human rotavirus (HRV). ELISA, dot immunobinding assay, cell protection assay, solid-phase assay and immunohistochemistry method were applied. BRV-R-mAb bound both anti-BRV IgG and anti-HRV IgG respectively and could protect MA 104 cells against BRV and HRV challenges. Immunohistochemistry test showed that there were rotavirus receptors on the surfaces of foetal intestinal, tracheal mucosa and MA 104 cells membrane. We purified the rotavirus receptors on MA 104 ceils, which could bind both BRV and HRV in vitro. It is concluded that BRV receptor and HRV receptor are homogenous proteins and can be recognized by both BRV and HRV.

  9. Melatonin Receptor Genes in Vertebrates

    Directory of Open Access Journals (Sweden)

    Hua Dong Yin

    2013-05-01

    Full Text Available Melatonin receptors are members of the G protein-coupled receptor (GPCR family. Three genes for melatonin receptors have been cloned. The MT1 (or Mel1a or MTNR1A and MT2 (or Mel1b or MTNR1B receptor subtypes are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (or MTNR1C, has been identified in fish, amphibians and birds. Another melatonin related orphan receptor, GPR50, which does not bind melatonin, is found exclusively in mammals. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. This hormone acts systemically in numerous organs. In the brain, it is involved in the regulation of various neural and endocrine processes, and it readjusts the circadian pacemaker, the suprachiasmatic nucleus. This article reviews recent studies of gene organization, expression, evolution and mutations of melatonin receptor genes of vertebrates. Gene polymorphisms reveal that numerous mutations are associated with diseases and disorders. The phylogenetic analysis of receptor genes indicates that GPR50 is an outgroup to all other melatonin receptor sequences. GPR50 may have separated from a melatonin receptor ancestor before the split between MTNR1C and the MTNR1A/B ancestor.

  10. Flavivirus Entry Receptors: An Update

    Directory of Open Access Journals (Sweden)

    Manuel Perera-Lecoin

    2013-12-01

    Full Text Available Flaviviruses enter host cells by endocytosis initiated when the virus particles interact with cell surface receptors. The current model suggests that flaviviruses use at least two different sets of molecules for infectious entry: attachment factors that concentrate and/or recruit viruses on the cell surface and primary receptor(s that bind to virions and direct them to the endocytic pathway. Here, we present the currently available knowledge regarding the flavivirus receptors described so far with specific attention to C-type lectin receptors and the phosphatidylserine receptors, T-cell immunoglobulin and mucin domain (TIM and TYRO3, AXL and MER (TAM. Their role in flavivirus attachment and entry as well as their implication in the virus biology will be discussed in depth.

  11. Angiotensin II receptors in testes

    Energy Technology Data Exchange (ETDEWEB)

    Millan, M.A.; Aguilera, G.

    1988-05-01

    Receptors for angiotensin II (AII) were identified and characterized in testes of rats and several primate species. Autoradiographic analysis of the binding of 125I-labeled (Sar1,Ile8)AII to rat, rhesus monkey, cebus monkey, and human testicular slide-mounted frozen sections indicated specific binding to Leydig cells in the interstitium. In rat collagenase-dispersed interstitial cells fractionated by Percoll gradient, AII receptor content was parallel to that of hCG receptors, confirming that the AII receptors are in the Leydig cells. In rat dispersed Leydig cells, binding was specific for AII and its analogs and of high affinity (Kd, 4.8 nM), with a receptor concentration of 15 fmol/10(6) cells. Studies of AII receptors in rat testes during development reveals the presence of high receptor density in newborn rats which decreases toward the adult age (4934 +/- 309, 1460 +/- 228, 772 +/- 169, and 82 +/- 12 fmol/mg protein at 5, 15, 20, and 30 days of age, respectively) with no change in affinity. At all ages receptors were located in the interstitium, and the decrease in binding was parallel to the decrease in the interstitial to tubular ratio observed with age. AII receptor properties in membrane-rich fractions from prepuberal testes were similar in the rat and rhesus monkey. Binding was time and temperature dependent, reaching a plateau at 60 min at 37 C, and was increased by divalent cations, EGTA, and dithiothreitol up to 0.5 mM. In membranes from prepuberal monkey testes, AII receptors were specific for AII analogs and of high affinity (Kd, 4.2 nM) with a receptor concentration of 7599 +/- 1342 fmol/mg protein. The presence of AII receptors in Leydig cells in rat and primate testes in conjunction with reports of the presence of other components of the renin-angiotensin system in the testes suggests that the peptide has a physiological role in testicular function.

  12. Uncompetitive antagonism of AMPA receptors

    DEFF Research Database (Denmark)

    Andersen, Trine F; Tikhonov, Denis B; Bølcho, Ulrik;

    2006-01-01

    Philanthotoxins are uncompetitive antagonists of Ca2+-permeable AMPA receptors presumed to bind to the pore-forming region, but a detailed molecular mechanism for this interaction is missing. Here a small library of novel philanthotoxins was designed and synthesized using a solid-phase strategy. ...... polyamine toxins antagonize the AMPA receptor ion channel and provide the basis for rational development of uncompetitive antagonists of AMPA receptors....

  13. GABAρ1/GABAAα1 receptor chimeras to study receptor desensitization

    Science.gov (United States)

    Martínez-Torres, Ataúlfo; Demuro, Angelo; Miledi, Ricardo

    2000-01-01

    γ-Aminobutyrate type C (GABAC) receptors are ligand-gated ion channels that are expressed preponderantly in the vertebrate retina and are characterized, among other things, by a very low rate of desensitization and resistance to the specific GABAA antagonist bicuculline. To examine which structural elements determine the nondesensitizing character of the human homomeric ρ1 receptor, we used a combination of gene chimeras and electrophysiology of receptors expressed in Xenopus oocytes. Two chimeric genes were constructed, made up of portions of the ρ1-subunit and of the α1-subunit of the GABAA receptor. When expressed in Xenopus oocytes, one chimeric gene (ρ1/α1) formed functional homooligomeric receptors that were fully resistant to bicuculline and were blocked by the specific GABAC antagonist (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid and by zinc. Moreover, these chimeric receptors had a fast-desensitizing component, even faster than that of heterooligomeric GABAA receptors, in striking contrast to the almost nil desensitization of wild-type ρ1 (wt ρ1) receptors. To see whether the fast-desensitizing characteristic of the chimera was determined by the amino acids forming the ion channels, we replaced the second transmembrane segment (TM2) of ρ1 by that of the α1-subunit of GABAA. Although the α1-subunit forms fast-desensitizing receptors when coexpressed with other GABAA subunits, the sole transfer of the α1TM2 segment to ρ1 was not sufficient to form desensitizing receptors. All this suggests that the slow-desensitizing trait of ρ1 receptors is determined by a combination of several interacting domains along the molecule. PMID:10725369

  14. Renal dopamine receptors and hypertension.

    Science.gov (United States)

    Hussain, Tahir; Lokhandwala, Mustafa F

    2003-02-01

    Dopamine has been recognized as an important modulator of central as well as peripheral physiologic functions in both humans and animals. Dopamine receptors have been identified in a number of organs and tissues, which include several regions within the central nervous system, sympathetic ganglia and postganglionic nerve terminals, various vascular beds, the heart, the gastrointestinal tract, and the kidney. The peripheral dopamine receptors influence cardiovascular and renal function by decreasing afterload and vascular resistance and promoting sodium excretion. Within the kidney, dopamine receptors are present along the nephron, with highest density on proximal tubule epithelial cells. It has been reported that there is a defective dopamine receptor, especially D(1) receptor function, in the proximal tubule of various animal models of hypertension as well as in humans with essential hypertension. Recent reports have revealed the site of and the molecular mechanisms responsible for the defect in D(1) receptors in hypertension. Moreover, recent studies have also demonstrated that the disruption of various dopamine receptor subtypes and their function produces hypertension in rodents. In this review, we present evidence that dopamine and dopamine receptors play an important role in regulating renal sodium excretion and that defective renal dopamine production and/or dopamine receptor function may contribute to the development of various forms of hypertension.

  15. Pharmacological maintenance treatments of opiate addiction.

    Science.gov (United States)

    Bell, James

    2014-02-01

    For people seeking treatment, the course of heroin addiction tends to be chronic and relapsing, and longer duration of treatment is associated with better outcomes. Heroin addiction is strongly associated with deviant behaviour and crime, and the objectives in treating heroin addiction have been a blend of humane support, rehabilitation, public health intervention and crime control. Reduction in street heroin use is the foundation on which all these outcomes are based. The pharmacological basis of maintenance treatment of dependent individuals is to minimize withdrawal symptoms and attenuate the reinforcing effects of street heroin, leading to reduction or cessation of street heroin use. Opioid maintenance treatment can be moderately effective in suppressing heroin use, although deviations from evidence-based approaches, particularly the use of suboptimal doses, have meant that treatment as delivered in practice may have resulted in poorer outcomes than predicted by research. Methadone treatment has been 'programmatic', with a one-size-fits-all approach that in part reflects the perceived need to impose discipline on deviant individuals. However, differences in pharmacokinetics and in side-effects mean that many patients do not respond optimally to methadone. Injectable diamorphine (heroin) provides a more reinforcing medication for some 'nonresponders' and can be a valuable option in the rehabilitation of demoralized, socially excluded individuals. Buprenorphine, a partial agonist, is a less reinforcing medication with different side-effects and less risk of overdose. Not only is it a different medication, but also it can be used in a different paradigm of treatment, office-based opioid treatment, with less structure and offering greater patient autonomy.

  16. Endogenous opiates mediate radiogenic behavioral change

    Energy Technology Data Exchange (ETDEWEB)

    Mickley, G.A.; Stevens, K.E.; White, G.A.; Gibbs, G.L.

    1983-07-10

    Exposure of C57BL/6J mice to ionizing radiation caused stereotypical locomotor hyperactivity similar to that produced by morphine. Naloxone administration prevented this radiation-induced behavioral activation. These results support the hypothesis that endorphins are involved in some aspects of radiogenic behavioral change.

  17. Accelerated neuroregulation for therapy of opiate dependency

    Directory of Open Access Journals (Sweden)

    S. Sunatrio

    2004-03-01

    Full Text Available Acute weaning from chronic opioid abuse during general anesthesia is usually followed by adrenergic outflow effects. This article is to report our experience with accelerated neuroregulation that reverses the physical and psychological dependency. After a comprehensive psychological and medical examination, 361 heroin dependent patients were admitted to ICU to be hospitalized for a full 24 or 36 hours, including a 6 hour pre-procedure medication process (solbutamol, clonidine, diazepam, ranitidine, omeprazole, vitamin C, octreotide, and ondansetron. Anesthesia was induced with midazolam and propofol iv and maintained with propofol infusion. Naltrexon, clonidine, octreotide, and diazepam were then administered. Anesthesia was maintained for 3 ½ - 5 hours depending on severity of withdrawal symptoms precipitated by naltrexone. Analgetics and sedatives were given as needed afterwards. Upon discharge on the following day, patient was prescribed a regimen of oral naltrexone for 10-12 months. All 361 patients were successfully detoxified without any adverse anesthetic events. The side effects encountered were fatigue, insomnia, drowsy, shivering, abdominal pain, nausea, diarrhoea, myalgia, goose bumps and uncomfortable feeling. In most of the patients these symptoms disappeared without any treatment. Symptomatic treatments were needed in 32.7% of patients. In all 166 patients who completed their naltrexone maintenance treatment, craving disappeared in the 10th month. The main problem was the low patient compliance to oral naltrexone, so that only 45.9% of the patients completed their therapy. Conclusion: Accelerated neuroregulation which includes naltrexone maintenance treatment (10-12 months was highly effective to detoxify and to abolish craving in the heroin dependent patients. (Med J Indones 2004; 13: 53-8Keywords: detoxification, craving management

  18. [Opiates, harm reduction and polysubstance abuse].

    Science.gov (United States)

    Touzeau, Didier; Courty, Pascal

    2012-12-01

    Opioid dependence is a chronic metabolic brain disease and several individual, sociological and biological factors are implicated in its development. Program (needle exchange, low threshold access to treatment) prevent harms associated with opioid use (HIV, overdose…). Effective treatment involves a set of pharmacological and psychosocial interventions. The benefits of maintenance programmes increase as long as the person remains in treatment (many years). Relapse is a symptom of the disorder or a sign of abstinence failure. Treatment aims to improve quality of life in a comprehensive and individualised assessment.

  19. Leptin and its receptors.

    Science.gov (United States)

    Wada, Nobuhiro; Hirako, Satoshi; Takenoya, Fumiko; Kageyama, Haruaki; Okabe, Mai; Shioda, Seiji

    2014-11-01

    Leptin is mainly produced in the white adipose tissue before being secreted into the blood and transported across the blood-brain barrier. Leptin binds to a specific receptor (LepR) that has numerous subtypes (LepRa, LepRb, LepRc, LepRd, LepRe, and LepRf). LepRb, in particular, is expressed in several brain nuclei, including the arcuate nucleus, the paraventricular nucleus, and the dorsomedial, lateral and ventromedial regions of the hypothalamus. LepRb is also co-expressed with several neuropeptides, including proopiomelanocortin, neuropeptide Y, galanin, galanin-like peptide, gonadotropin-releasing hormone, tyrosine hydroxylase and neuropeptide W. Functionally, LepRb induces activation of the JAK2/ERK, /STAT3, /STAT5 and IRS/PI3 kinase signaling cascades, which are important for the regulation of energy homeostasis and appetite in mammals. In this review, we discuss the structure, genetics and distribution of the leptin receptors, and their role in cell signaling mechanisms.

  20. Axonal GABAA receptors.

    Science.gov (United States)

    Trigo, Federico F; Marty, Alain; Stell, Brandon M

    2008-09-01

    Type A GABA receptors (GABA(A)Rs) are well established as the main inhibitory receptors in the mature mammalian forebrain. In recent years, evidence has accumulated showing that GABA(A)Rs are prevalent not only in the somatodendritic compartment of CNS neurons, but also in their axonal compartment. Evidence for axonal GABA(A)Rs includes new immunohistochemical and immunogold data: direct recording from single axonal terminals; and effects of local applications of GABA(A)R modulators on action potential generation, on axonal calcium signalling, and on neurotransmitter release. Strikingly, whereas presynaptic GABA(A)Rs have long been considered inhibitory, the new studies in the mammalian brain mostly indicate an excitatory action. Depending on the neuron that is under study, axonal GABA(A)Rs can be activated by ambient GABA, by GABA spillover, or by an autocrine action, to increase either action potential firing and/or transmitter release. In certain neurons, the excitatory effects of axonal GABA(A)Rs persist into adulthood. Altogether, axonal GABA(A)Rs appear as potent neuronal modulators of the mammalian CNS.