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Sample records for prenatal cocaine alcohol

  1. Social behavior of offspring following prenatal cocaine exposure in rodents: a comparison with prenatal alcohol

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    Sonya Krishna Sobrian

    2011-11-01

    Full Text Available Clinical and experimental reports suggest that prenatal cocaine exposure(PCEalters the offsprings’ social interactions with caregivers and conspecifics. Children exposed to prenatal cocaine show deficits in caregiver attachment and play behavior. In animal models,a developmental pattern of effects that range from deficits in play and social interaction during adolescence, to aggressive reactions during competition in adulthood is seen. This review will focus primarily on the effects of PCE on social behaviors involving conspecifics in animal models. Social relationships are critical to the developing organism; maternally-directed interactions are necessary for initial survival. Juvenile rats deprived of play behavior, one of the earliest forms of non-mother directed social behaviors in rodents, show deficits in learning tasks and sexual competence. Social behavior is inherently conmplex. Because the emergence of appropriate social skills involves the interplay between various conceptual and biological facets of behavior and social information, it may be a particularly sensitive measure of prenatal insult. The social behavior surveyed include social interactions, play behavior/fighting, scent marking and aggressive behavior in the offspring, as well as aspects of maternal behavior. The goal is to determine if there is a consensus of results in the literature with respect to PCE and social behaviors, and to discuss discrepant findings in terms of exposure models, the paradigms and dependent variables, as well as housing conditions, and the sex and age of the offspring at testing. As there is increasing evidence that deficits in social behavior may be sequelae of developmental exposure alcohol, we compare changes in social behaviors reported for prenatal alcohol with those reported for prenatal cocaine. Shortcomings in the both literatures are identified and addressed in an effort to improve the translational value of future experimentation.

  2. Prenatal and postnatal cocaine exposure predict teen cocaine use.

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    Delaney-Black, Virginia; Chiodo, Lisa M; Hannigan, John H; Greenwald, Mark K; Janisse, James; Patterson, Grace; Huestis, Marilyn A; Partridge, Robert T; Ager, Joel; Sokol, Robert J

    2011-01-01

    Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n=316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Prenatal Cocaine Exposure and Childhood Obesity at Nine Years

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    LaGasse, Linda L.; Gaskins, Ronnesia B.; Bada, Henrietta S.; Shankaran, Seetha; Liu, Jing; Lester, Barry M.; Bauer, Charles R.; Higgins, Rosemary D.; Das, Abhik; Roberts, Mary

    2010-01-01

    Little is known about the association between prenatal cocaine exposure and obesity. We tested whether prenatal cocaine exposure increases the likelihood of obesity in 561 9-year-old term children from the Maternal Lifestyle Study (MLS). Overall, 21.6% of children met criterion for obesity (body mass index [BMI] ≥ 95th percentile, age and sex-specific). While there was no overall cocaine effect on obesity, multivariate logistic analysis revealed that children exposed to cocaine but not alcohol were 4 times more likely to be obese (OR 4.11, CI 2.04–9.76) than children not exposed to either drug. No increase in obesity prevalence was found in children exposed to alcohol but not cocaine (OR 1.08, CI .59–1.93) or both (OR 1.21, CI 0.66–2.22). Alcohol exposure may attenuate the effect of cocaine exposure on obesity. Increased obesity associated with cocaine but not alcohol exposure was first observed at 7 years. BMI was also elevated from 3 to 9 years in children exposed to cocaine but not alcohol, due to increasing weight but normal height. Prenatal exposure to cocaine may alter the neuroendocrine system and metabolic processes resulting in increased weight gain and childhood obesity. PMID:21109003

  4. Growth, development, and behavior in early childhood following prenatal cocaine exposure: a systematic review.

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    Frank, D A; Augustyn, M; Knight, W G; Pell, T; Zuckerman, B

    2001-03-28

    to be specific effects of in utero cocaine exposure are correlated with other factors, including prenatal exposure to tobacco, marijuana, or alcohol, and the quality of the child's environment. Further replication is required of preliminary neurologic findings.

  5. Osteonecrosis following alcohol, cocaine, and steroid use.

    LENUS (Irish Health Repository)

    Ziraldo, Laura

    2012-02-01

    Alcohol, steroids and cocaine have all been shown to be independent risk factors for osteonecrosis when taken in excess. Here we present a case of a young girl who developed debilitating osteonecrosis secondary to low doses of alcohol, steroids and cocaine. We feel it is important to highlight to those caring for such patients of the potential devastating complication of these three agents.

  6. Prenatal Cocaine Exposure Alters Cortisol Stress Reactivity in 11 Year Old Children

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    Lester, Barry M.; LaGasse, Linda L.; Shankaran, Seetha; Bada, Henrietta S.; Bauer, Charles R.; Lin, Richard; Das, Abhik; Higgins, Rosemary

    2011-01-01

    Objective Determine the association between prenatal cocaine exposure and postnatal environmental adversity on salivary cortisol stress reactivity in school aged children. Study design Subjects included 743 11 year old children (n=320 cocaine exposed; 423 comparison) followed since birth in a longitudinal prospective multisite study. Saliva samples were collected to measure cortisol at baseline and after a standardized procedure to induce psychological stress. Children were divided into those who showed an increase in cortisol from baseline to post stress and those who showed a decrease or blunted cortisol response. Covariates measured included site, birthweight, maternal pre and postnatal use of alcohol, tobacco or marijuana, social class, changes in caretakers, maternal depression and psychological symptoms, domestic and community violence, child abuse and quality of the home. Results With adjustment for confounding variables, cortisol reactivity to stress was more likely to be blunted in children with prenatal cocaine exposure. Cocaine exposed children exposed to domestic violence showed the strongest effects. Conclusion The combination of prenatal cocaine exposure and an adverse postnatal environment could down regulate the hypothalamic-pituitary-adrenal axis (HPA) resulting in the blunted cortisol response to stress possibly increasing risk for later psychopathology and adult disease. PMID:20400094

  7. Prenatal cocaine exposure effects on arousal-modulated attention during the neonatal period.

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    Karmel, B Z; Gardner, J M

    1996-07-01

    The organization of arousal and attention as a function of intrauterine cocaine exposure was investigated in 180 normal nursery infants prior to hospital discharge and at 1 month of age. This was done by studying visual looking preferences when infants were in three arousal conditions: less aroused (after feeding); more aroused-endogenous (before feeding); and more aroused-exogenous (after feeding but including 8-Hz visual stimulation prior to each visual preference trial). The stimuli were light panels illuminated at three temporal frequencies between 1 and 8 Hz presented in pairs using a balanced presentation series of trials. Infants not exposed to cocaine demonstrated strong arousal-modulated attention, preferring faster frequencies when less aroused and slower frequencies when more aroused in both endogenous and exogenous conditions. In contrast, cocaine-exposed infants showed a lack of arousal-modulated attention and preferred faster frequencies of stimulation regardless of arousal condition. Similar differences in arousal-modulated attention as a function of cocaine exposure were obtained at 1 month after birth, indicating that these effects lasted longer than would be reasonable to attribute to the active presence of cocaine or its metabolites. This form of stimulus-seeking behavior was shown to be independent of confounding factors associated with prenatal cocaine exposure such as the absence of prenatal care, alcohol use, minority status, or gender, as well as mediating factors associated with growth such as birthweight. A direct and more chronic effect of intrauterine cocaine exposure on arousal-modulated attention and presumably on the developing CNS therefore was supported.

  8. Prenatal IV Cocaine: Alterations in Auditory Information Processing

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    Charles F. Mactutus

    2011-06-01

    Full Text Available One clue regarding the basis of cocaine-induced deficits in attentional processing is provided by the clinical findings of changes in the infants’ startle response; observations buttressed by neurophysiological evidence of alterations in brainstem transmission time. Using the IV route of administration and doses that mimic the peak arterial levels of cocaine use in humans, the present study examined the effects of prenatal cocaine on auditory information processing via tests of the acoustic startle response (ASR, habituation, and prepulse inhibition (PPI in the offspring. Nulliparous Long-Evans female rats, implanted with an IV access port prior to breeding, were administered saline, 0.5, 1.0, or 3.0 mg/kg/injection of cocaine HCL (COC from gestation day (GD8-20 (1x/day-GD8-14, 2x/day-GD15-20. COC had no significant effects on maternal/litter parameters or growth of the offspring. At 18-20 days of age, one male and one female, randomly selected from each litter displayed an increased ASR (>30% for males at 1.0 mg/kg and >30% for females at 3.0 mg/kg. When reassessed in adulthood (D90-100, a linear dose-response increase was noted on response amplitude. At both test ages, within-session habituation was retarded by prenatal cocaine treatment. Testing the females in diestrus vs. estrus did not alter the results. Prenatal cocaine altered the PPI response function across interstimulus interval (ISI and induced significant sex-dependent changes in response latency. Idazoxan, an alpha2-adrenergic receptor antagonist, significantly enhanced the ASR, but less enhancement was noted with increasing doses of prenatal cocaine. Thus, in utero exposure to cocaine, when delivered via a protocol designed to capture prominent features of recreational usage, causes persistent, if not permanent, alterations in auditory information processing, and suggests dysfunction of the central noradrenergic circuitry modulating, if not mediating, these responses.

  9. Prenatal cocaine exposure uncouples mGluR1 from Homer1 and Gq Proteins.

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    Kalindi Bakshi

    Full Text Available Cocaine exposure during gestation causes protracted neurobehavioral changes consistent with a compromised glutamatergic system. Although cocaine profoundly disrupts glutamatergic neurotransmission and in utero cocaine exposure negatively affects metabotropic glutamate receptor-type 1 (mGluR1 activity, the effect of prenatal cocaine exposure on mGluR1 signaling and the underlying mechanism responsible for the prenatal cocaine effect remain elusive. Using brains of the 21-day-old (P21 prenatal cocaine-exposed rats, we show that prenatal cocaine exposure uncouples mGluR1s from their associated synaptic anchoring protein, Homer1 and signal transducer, Gq/11 proteins leading to markedly reduced mGluR1-mediated phosphoinositide hydrolysis in frontal cortex (FCX and hippocampus. This prenatal cocaine-induced effect is the result of a sustained protein kinase C (PKC-mediated phosphorylation of mGluR1 on the serine residues. In support, phosphatase treatment of prenatal cocaine-exposed tissues restores whereas PKC-mediated phosphorylation of saline-treated synaptic membrane attenuates mGluR1 coupling to both Gq/11 and Homer1. Expression of mGluR1, Homer1 or Gα proteins was not altered by prenatal cocaine exposure. Collectively, these data indicate that prenatal cocaine exposure triggers PKC-mediated hyper-phosphorylation of the mGluR1 leading to uncoupling of mGluR1 from its signaling components. Hence, blockade of excessive PKC activation may alleviate abnormalities in mGluR1 signaling and restores mGluR1-regulated brain functions in prenatal cocaine-exposed brains.

  10. Prenatal cocaine exposure uncouples mGluR1 from Homer1 and Gq Proteins.

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    Bakshi, Kalindi; Parihar, Raminder; Goswami, Satindra K; Walsh, Melissa; Friedman, Eitan; Wang, Hoau-Yan

    2014-01-01

    Cocaine exposure during gestation causes protracted neurobehavioral changes consistent with a compromised glutamatergic system. Although cocaine profoundly disrupts glutamatergic neurotransmission and in utero cocaine exposure negatively affects metabotropic glutamate receptor-type 1 (mGluR1) activity, the effect of prenatal cocaine exposure on mGluR1 signaling and the underlying mechanism responsible for the prenatal cocaine effect remain elusive. Using brains of the 21-day-old (P21) prenatal cocaine-exposed rats, we show that prenatal cocaine exposure uncouples mGluR1s from their associated synaptic anchoring protein, Homer1 and signal transducer, Gq/11 proteins leading to markedly reduced mGluR1-mediated phosphoinositide hydrolysis in frontal cortex (FCX) and hippocampus. This prenatal cocaine-induced effect is the result of a sustained protein kinase C (PKC)-mediated phosphorylation of mGluR1 on the serine residues. In support, phosphatase treatment of prenatal cocaine-exposed tissues restores whereas PKC-mediated phosphorylation of saline-treated synaptic membrane attenuates mGluR1 coupling to both Gq/11 and Homer1. Expression of mGluR1, Homer1 or Gα proteins was not altered by prenatal cocaine exposure. Collectively, these data indicate that prenatal cocaine exposure triggers PKC-mediated hyper-phosphorylation of the mGluR1 leading to uncoupling of mGluR1 from its signaling components. Hence, blockade of excessive PKC activation may alleviate abnormalities in mGluR1 signaling and restores mGluR1-regulated brain functions in prenatal cocaine-exposed brains.

  11. Comparing attitudes about legal sanctions and teratogenic effects for cocaine, alcohol, tobacco and caffeine: A randomized, independent samples design

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    Alanis Kelly L

    2006-02-01

    Full Text Available Abstract Background Establishing more sensible measures to treat cocaine-addicted mothers and their children is essential for improving U.S. drug policy. Favorable post-natal environments have moderated potential deleterious prenatal effects. However, since cocaine is an illicit substance having long been demonized, we hypothesized that attitudes toward prenatal cocaine exposure would be more negative than for licit substances, alcohol, nicotine and caffeine. Further, media portrayals about long-term outcomes were hypothesized to influence viewers' attitudes, measured immediately post-viewing. Reducing popular crack baby stigmas could influence future policy decisions by legislators. In Study 1, 336 participants were randomly assigned to 1 of 4 conditions describing hypothetical legal sanction scenarios for pregnant women using cocaine, alcohol, nicotine or caffeine. Participants rated legal sanctions against pregnant women who used one of these substances and risk potential for developing children. In Study 2, 139 participants were randomly assigned to positive, neutral and negative media conditions. Immediately post-viewing, participants rated prenatal cocaine-exposed or non-exposed teens for their academic performance and risk for problems at age18. Results Participants in Study 1 imposed significantly greater legal sanctions for cocaine, perceiving prenatal cocaine exposure as more harmful than alcohol, nicotine or caffeine. A one-way ANOVA for independent samples showed significant differences, beyond .0001. Post-hoc Sheffe test illustrated that cocaine was rated differently from other substances. In Study 2, a one-way ANOVA for independent samples was performed on difference scores for the positive, neutral or negative media conditions about prenatal cocaine exposure. Participants in the neutral and negative media conditions estimated significantly lower grade point averages and more problems for the teen with prenatal cocaine exposure

  12. [Cocaine and trisomy 8 associated with prenatal diagnosis of corpus callosum agenesis].

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    Gonzales, E; Caeymaex, L; Aboura, A; Vial, M; De Laveaucoupet, J; Labrune, P; Tachdjian, G

    2005-12-01

    We report the case of a newborn presenting an agenesis of corpus callosum (ACC) discovered in the prenatal period and initially related to cocaine exposure during the first trimester of gestation. The cytogenetic analysis revealed a trisomy 8 mosaicism. The putative role of prenatal cocaine exposure and mosaicism for chromosome 8 in ACC are discussed. This report emphasizes the specific analysis of chromosome 8 by using fluorescence in situ hybridization as a complement to routine cytogenetic analysis for prenatal diagnosis of ACC.

  13. Prenatal Alcohol Exposure and Cortical Angiogenesis

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    J Gordon Millichap

    2013-02-01

    Full Text Available Researchers at Normandy University, and Rouen and Brest Universities, France studied the effects of prenatal alcohol exposure on the cortical microvascular and the action of alcohol, glutamate, and vascular endothelial growth factor A (VEGF on activity, plasticity, and survival of microvessels in mice.

  14. Effect of prenatal cocaine on early postnatal thermoregulation and ultrasonic vocalization production

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    Matthew Stephen McMurray

    2013-11-01

    Full Text Available Prenatal cocaine exposure can alter the postnatal care received by rat pups. Such effects could be caused in part by alterations in pup-produced stimuli that elicit early postnatal maternal care. Pup ultrasonic vocalizations are thought to be a particularly salient stimulus, and when paired with other cues, may elicit maternal attention. Cocaine is known to acutely alter thermoregulatory and cardiac function, thus prenatal cocaine may affect vocalizations through altering these functions. The data presented here determine the impact of full term prenatal cocaine exposure , saline exposure, or no exposure on thermogenic capacity, cardiac function, and the resulting ultrasonic vocalizations across the early postnatal period (days 1-5. Results indicated that while sharing many similar characteristics with saline-exposed and untreated animals, prenatal cocaine exposure was associated with specific alterations in vocalization characteristics on postnatal day 1 (PND 1, including call amplitude. Furthermore, numerous spectral parameters of their vocalizations were found altered on PND 3, including rate, call duration, and frequency, while no alterations were found on PND 5. Additionally, cocaine-exposed pups also showed a reduced thermoregulatory capacity compared to saline animals and reduced cardiac mass compared to untreated animals on PND 5. Together, these findings indicate that prenatal cocaine may be altering the elicitation of maternal care through its impact on vocalizations and thermoregulation, and suggests a potential mechanism for these effects through cocaine’s impact on developing stress systems.

  15. Differences between Alcoholics and Cocaine Addicts Seeking Treatment.

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    López-Goñi, José J; Fernández-Montalvo, Javier; Arteaga, Alfonso

    2015-03-03

    This study explored the characteristics of a representative sample of patients who were addicted to either alcohol or cocaine, comparing the profiles of both types of drug users. A sample of 234 addicted patients (109 alcoholics and 125 cocaine addicts) who sought outpatient treatment in a Spanish clinical centre was assessed. Data on socio-demographic, consumption, psychopathological and maladjustment characteristics were collected using the European Addiction Severity Index (EuropASI), the Symptom Checklist-90-Revised (SCL-90-R) and the Millon Clinical Multiaxial Inventory (MCMI-II). Demographically, differences were observed with regard to age (alcoholics were older than cocaine addicts; t = 12.2, p = .001), employment (the alcoholic group had more labor problems; χ 2 = 6.2, p = .045) and family consequences (worse in alcoholics; t = 2.3, p = .025). The EuropASI results showed statistically significant differences in addiction severity, with alcoholics showing a greater severity than cocaine addicts. In terms of psychopathology, alcoholics presented more associated symptomatology than cocaine addicts. According to these results, patients with alcohol dependence have a different profile from patients with cocaine dependence, resulting in different repercussions for important areas of their lives. These differences should be taken into account when standard treatments for addiction are implemented.

  16. Prenatal and acute cocaine exposure affects neural responses and habituation to visual stimuli

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    Elizabeth Brooke Riley

    2015-08-01

    Full Text Available Psychostimulants have many effects on visual function, from adverse, following acute and prenatal exposure to therapeutic, on attention deficit. To determine the impact of prenatal and acute cocaine exposure on visual processing, we studied neuronal responses to visual stimuli in two brain regions of a transgenic larval zebrafish expressing the calcium indicator GCaMP-HS. We found that both red light (LF and dark (DF flashes elicited similar responses in the optic tectum neuropil (TOn, while the dorsal telencephalon (dTe responded only to LF. Acute cocaine (0.5 μM reduced neuronal responses to LF in both brain regions but did not affect responses to DF. Repeated stimulus presentation led to habituation of dTe neurons to LF. Acute cocaine prevented habituation. TOn habituated to DF, but not LF, and DF habituation was not modified by cocaine. Remarkably, prenatal cocaine exposure prevented the effects of acute cocaine on LF response amplitude and habituation later in development in both brain regions, but did not affect DF responses. We discovered that, in spite of similar neural responses to LF and DF in the TO (superior colliculus in mammals, responses to LF are more complex, involving dTe (homologous to the cerebral cortex, and are more vulnerable to cocaine. Our results demonstrate that acute cocaine exposure affects visual processing differentially by brain region, and that prenatal cocaine exposure modifies zebrafish visual processing in multiple structures in a stimulus-dependent manner. These findings are in accordance with the major role that the optic tectum and cerebral cortex play in sustaining visual attention, and support the hypothesis that modification of these areas by prenatal cocaine exposure may be responsible for visual deficits noted in humans. This model offers new methodological approaches for studying the adverse and therapeutic effects of psychostimulants on attention, and for the development of new pharmacological

  17. A comparison of motivations for use among users of crack cocaine and cocaine powder in a sample of simultaneous cocaine and alcohol users.

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    Martin, Gina; Macdonald, Scott; Pakula, Basia; Roth, Eric A

    2014-03-01

    This study examined the motivations for using cocaine and alcohol comparing those who primarily smoked crack and those who primarily used cocaine powder when using simultaneously with alcohol. Motivations examined included: 1) to cope with a negative affect, 2) enhancement, 3) to be social and 4) to conform. The research design was a cross-sectional study in which clients in treatment for cocaine and alcohol problems completed a self-administered questionnaire about their substance use. Among those who primarily smoked crack or snorted cocaine when also using alcohol (n=153), there were 93 participants who reported primarily snorting cocaine and 60 participants who primarily reported smoking crack. Bivariate analyses found that those who primarily smoked crack reported lower social motivations to use alcohol and cocaine. When adjusting for other covariates in a multivariate analysis, social motivation was still significantly different between groups. Additionally, those who primarily smoked crack were more likely to be older, report higher cocaine dependence severity, be unemployed and were less likely to have completed some post-secondary education, than those who primarily snorted cocaine. No differences were found in enhancement, coping or conformity motivations between the two groups. These results suggest that simultaneous cocaine and alcohol use may have social importance to those who primarily snort cocaine, but that this importance is less evident to those who smoke crack. Consequently, future studies examining motivations for simultaneous cocaine and alcohol use should distinguish between different routes of cocaine administration.

  18. Abnormal regulation for progesterone production in placenta with prenatal cocaine exposure in rats.

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    Wu, L; Yan, J; Qu, S C; Feng, Y Q; Jiang, X L

    2012-12-01

    Cocaine abuse in pregnant women is currently a significant public hygiene problem and is tightly associated with elevated risk for preterm delivery. Placental steroidogenesis especially progesterone production was essential for success and maintenance of pregnancy in humans and rodents. In the present study, we determined the impact of prenatal cocaine exposure on pathways of placental progesterone synthesis in rats. Pregnant rats were treated cocaine twice daily (15 mg/kg/day) during the third trimester, and the maternal and fetal plasma progesterone and pregnenolone concentrations were detected. We also examined both the protein and mRNA expression of some key enzymes and regulators for progesterone production in placenta. Results showed that, after maternal cocaine use during pregnancy, progesterone and pregnenolone concentrations in both maternal and fetal rats were significantly decreased. Although prenatal cocaine exposure had no effects on placental 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1) expression, protein and mRNA expression of the cholesterol side-chain cleavage enzyme (P450scc/CYP11a) in placenta was significantly inhibited. Moreover, protein and mRNA expressions of MLN64 that regulating cholesterol transport and activating protein 2γ (AP2γ/Tfap2c) that controlling P450scc/CYP11a gene expression in placenta were both decreased following maternal cocaine use in pregnancy. Collectively, this study suggested that prenatal cocaine exposure could insult the placental progesterone production in rats possibly associated with the high risk for preterm delivery.

  19. Prenatal Cocaine Exposure and Body Mass Index and Blood Pressure at 9 Years of Age

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    Shankaran, Seetha; Bann, Carla; Bauer, Charles R.; Lester, Barry; Bada, Henrietta; Das, Abhik; Higgins, Rosemary; Poole, Ken; LaGasse, Linda; Hammond, Jane; Woldt, Eunice

    2010-01-01

    Background Prenatal cocaine exposure has been linked to intrauterine growth retardation and poor birth outcomes; little is known about the effects on longer-term medical outcomes, such as overweight status and hypertension in childhood. Our objective was to examine the association between prenatal cocaine exposure and body mass index and blood pressure at 9 years of age among children followed prospectively in a multi-site longitudinal study evaluating the impact of maternal lifestyle during pregnancy on childhood outcome. Design/Methods This analysis includes 880 children (277 cocaine exposed and 603 with no cocaine exposure) with blood pressure, height, and weight measurements at 9 years of age. Regression analyses were conducted to explore the relationship between prenatal cocaine exposure and body mass index and blood pressure at 9 years of age after controlling for demographics, other drug exposure, birth weight, maternal weight, infant postnatal weight gain, and childhood television viewing, exercise and dietary habits at 9 years. Path analyses were used to further explore these relationships. Results At 9 years of age, 15% of the children were pre-hypertensive and 19% were hypertensive; 16% were at risk for overweight status and 21% were overweight. A small percentage of women were exposed to high levels of prenatal cocaine throughout pregnancy. Among children born to these women, a higher body mass index was noted. Path analysis suggested that high cocaine exposure has an indirect effect on systolic and diastolic blood pressure that is mediated through its effect on body mass index. Conclusion High levels of in-utero cocaine exposure are a marker for elevated body mass index and blood pressure among children born full term. PMID:20486281

  20. Effects of Prenatal Cocaine Exposure on Special Education in School-Aged Children

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    Levine, Todd P.; Liu, Jing; Das, Abhik; Lester, Barry; Lagasse, Linda; Shankaran, Seetha; Bada, Henrietta S.; Bauer, Charles R.; Higgins, Rosemary

    2010-01-01

    OBJECTIVE The objective of this study was to evaluate the effects of prenatal cocaine exposure on special education at age 7 with adjustment for covariates. METHODS As part of the prospective, longitudinal, multisite study of children with prenatal cocaine exposure (Maternal Lifestyle Study), school records were reviewed for 943 children at 7 years to determine involvement in special education outcomes: (1) individualized education plan; (2) special education conditions; (3) support services; (4) special education classes; and (5) speech and language services. Logistic regression was used to examine the effect of prenatal cocaine exposure on these outcomes with environmental, maternal, and infant medical variables as covariates, as well as with and without low child IQ. RESULTS Complete data for each analysis model were available for 737 to 916 children. When controlling for covariates including low child IQ, prenatal cocaine exposure had a significant effect on individualized education plan. When low child IQ was not included in the model, prenatal cocaine exposure had a significant effect on support services. Male gender, low birth weight, white race, and low child IQ also predicted individualized education plan. Low birth weight and low child IQ were significant in all models. White race was also significant in speech and language services. Other covariate effects were model specific. When included in the models, low child IQ accounted for more of the variance and changed the significance of other covariates. CONCLUSIONS Prenatal cocaine exposure increased the likelihood of receiving an individualized education plan and support services, with adjustment for covariates. Low birth weight and low child IQ increased the likelihood of all outcomes. The finding that white children were more likely to get an individualized education plan and speech and language services could indicate a greater advantage in getting educational resources for this population. PMID

  1. Prenatal cocaine alters later responses to morphine in adult male mice.

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    Estelles, Josefina; Rodríguez-Arias, Marta; Maldonado, Concepción; Manzanedo, Carmen; Aguilar, María A; Miñarro, José

    2006-08-30

    Mice prenatally exposed to cocaine (25 mg/kg), physiological saline or non-treated during the last 6 days of pregnancy were evaluated as adults for the rewarding properties of 2 mg/kg of morphine, using the conditioned place preference (CPP) procedure. Likewise, isolated animals underwent a social interaction test with conspecifics after receiving the same morphine dose. Unlike control or animals pre-treated with saline, subjects prenatally treated with cocaine did not develop CPP with this dose of morphine. Only cocaine-exposed animals showed increased threat, avoidance and fleeing during the social encounter. No differences in motor effects of morphine were observed. Analysis of monoamines revealed effects of housing conditions, isolated animals having fewer DOPAC but higher levels of HVA than those grouped, but in both groups there was a decrease in DOPAC in cocaine- and saline-treated mice. Prenatal cocaine exposure decreases the response to the rewarding properties of drugs in mature offspring. They also implicate cocaine consumption during pregnancy could affect the response of offspring to take other drugs of abuse.

  2. Prenatal cocaine exposure decreases parvalbumin-immunoreactive neurons and GABA-to-projection neuron ratio in the medial prefrontal cortex.

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    McCarthy, Deirdre M; Bhide, Pradeep G

    2012-01-01

    Cocaine abuse during pregnancy produces harmful effects not only on the mother but also on the unborn child. The neurotransmitters dopamine and serotonin are known as the principal targets of the action of cocaine in the fetal and postnatal brain. However, recent evidence suggests that cocaine can impair cerebral cortical GABA neuron development and function. We sought to analyze the effects of prenatal cocaine exposure on the number and distribution of GABA and projection neurons (inhibitory interneurons and excitatory output neurons, respectively) in the mouse cerebral cortex. We found that the prenatal cocaine exposure decreased GABA neuron numbers and GABA-to-projection neuron ratio in the medial prefrontal cortex of 60-day-old mice. The neighboring prefrontal cortex did not show significant changes in either of these measures. However, there was a significant increase in projection neuron numbers in the prefrontal cortex but not in the medial prefrontal cortex. Thus, the effects of cocaine on GABA and projection neurons appear to be cortical region specific. The population of parvalbumin-immunoreactive GABA neurons was decreased in the medial prefrontal cortex following the prenatal cocaine exposure. The cocaine exposure also delayed the developmental decline in the volume of the medial prefrontal cortex. Thus, prenatal cocaine exposure produced persisting and region-specific effects on cortical cytoarchitecture and impaired the physiological balance between excitatory and inhibitory neurotransmission. These structural changes may underlie the electrophysiological and behavioral effects of prenatal cocaine exposure observed in animal models and human subjects.

  3. Neuropsychological performance of recently abstinent alcoholics and cocaine abusers.

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    Beatty, W W; Katzung, V M; Moreland, V J; Nixon, S J

    1995-03-01

    To examine possible influences of premorbid and comorbid factors on the neuropsychological test performance of recently abstinent (3-5 weeks) drug abusers, we studied 24 alcoholics, 23 cocaine abusers, and 22 healthy controls of comparable age and education. Both alcoholics and cocaine abusers performed significantly more poorly than controls on most measures of learning and memory, problem solving and abstraction and perceptual-motor speed, but the groups did not differ on the measure of sustained attention. Correlational analyses revealed no significant relationships between measures of childhood and residual hyperactivity and neuropsychological performance; scores on the Beck Depression Inventory were related only to performance on the Wisconsin Card Sorting Test. The findings indicate that abuse of cocaine or alcohol is associated with deficits on neuropsychological tests which cannot be attributed to specific premorbid or comorbid factors such as depression or childhood or residual attention deficit disorder.

  4. Prenatal and acute cocaine exposure affects neural responses and habituation to visual stimuli.

    Science.gov (United States)

    Riley, Elizabeth; Kopotiyenko, Konstantin; Zhdanova, Irina

    2015-01-01

    Psychostimulants have many effects on visual function, from adverse following acute and prenatal exposure to therapeutic on attention deficit. To determine the impact of prenatal and acute cocaine exposure on visual processing, we studied neuronal responses to visual stimuli in two brain regions of a transgenic larval zebrafish expressing the calcium indicator GCaMP-HS. We found that both red light (LF) and dark (DF) flashes elicited similar responses in the optic tectum neuropil (TOn), while the dorsal telencephalon (dTe) responded only to LF. Acute cocaine (0.5 μM) reduced neuronal responses to LF in both brain regions but did not affect responses to DF. Repeated stimulus presentation (RSP) led to habituation of dTe neurons to LF. Acute cocaine prevented habituation. TOn habituated to DF, but not LF, and DF habituation was not modified by cocaine. Remarkably, prenatal cocaine exposure (PCE) prevented the effects of acute cocaine on LF response amplitude and habituation later in development in both brain regions, but did not affect DF responses. We discovered that, in spite of similar neural responses to LF and DF in the TO (superior colliculus in mammals), responses to LF are more complex, involving dTe (homologous to the cerebral cortex), and are more vulnerable to cocaine. Our results demonstrate that acute cocaine exposure affects visual processing differentially by brain region, and that PCE modifies zebrafish visual processing in multiple structures in a stimulus-dependent manner. These findings are in accordance with the major role that the optic tectum and cerebral cortex play in sustaining visual attention, and support the hypothesis that modification of these areas by PCE may be responsible for visual deficits noted in humans. This model offers new methodological approaches for studying the adverse and therapeutic effects of psychostimulants on attention, and for the development of new pharmacological interventions.

  5. Learning disabilities and intellectual functioning in school-aged children with prenatal cocaine exposure.

    Science.gov (United States)

    Morrow, Connie E; Culbertson, Jan L; Accornero, Veronica H; Xue, Lihua; Anthony, James C; Bandstra, Emmalee S

    2006-01-01

    Risk for developing a learning disability (LD) or impaired intellectual functioning by age 7 was assessed in full-term children with prenatal cocaine exposure drawn from a cohort of 476 children born full term and enrolled prospectively at birth. Intellectual functioning was assessed using the Wechsler Intelligence Scale for Children-Third Edition (Wechsler, 1991) short form, and academic functioning was assessed using the Wechsler Individual Achievement Test (WIAT; Wechsler, 1993) Screener by examiners blind to exposure status. LDs were categorized based on ability-achievement discrepancy scores, using the regression-based predicted achievement method described in the WIAT manual. The sample in this report included 409 children (212 cocaine-exposed, 197 non-cocaine-exposed) from the birth cohort with available data. Cumulative incidence proportions and relative risk values were estimated using STATA software (Statacorp, 2003). No differences were found in the estimate of relative risk for impaired intellectual functioning (IQ below 70) between children with and without prenatal cocaine exposure (estimated relative risk = .95; 95% confidence interval [CI] = 0.65, 1.39; p = .79). The cocaine-exposed children had 2.8 times greater risk of developing a LD by age 7 than non-cocaine-exposed children (95% CI = 1.05, 7.67; p = .038; IQ >/= 70 cutoff). Results remained stable with adjustment for multiple child and caregiver covariates, suggesting that children with prenatal cocaine exposure are at increased risk for developing a learning disability by age 7 when compared to their non-cocaine-exposed peers.

  6. An overview of cocaethylene, an alcohol-derived, psychoactive, cocaine metabolite.

    Science.gov (United States)

    Landry, M J

    1992-01-01

    Cocaethylene is a psychoactive ethyl homologue of cocaine, and is formed exclusively during the coadministration of cocaine and alcohol. Not a natural alkaloid of the coca leaf, cocaethylene can be identified in the urine, blood, hair, and neurological and liver tissue samples of individuals who have consumed both cocaine and alcohol. With a pharmacologic profile similar to cocaine, it can block the dopamine transporter on dopaminergic presynaptic nerve terminals in the brain. It increases dopamine synaptic content, provoking enhanced postsynaptic receptor stimulation, resulting in euphoria, reinforcement, and self-administration. Equipotent to cocaine with regard to dopamine transporter affinity, cocaethylene appears to be far less potent than cocaine with regard to serotonin transporter binding. Lacking the serotonergic-related inhibitory mechanism, cocaethylene appears to be more euphorigenic and rewarding than cocaine. Synthesized and administered cocaethylene has a behavioral stimulation profile similar to cocaine. Cocaethylene has been shown to be less potent and equipotent to cocaine, and alcohol plus cocaine produces more stimulatory locomotor behavior in mice than either drug alone. Equipotent to cocaine with regard to primate reinforcement and self-administration, cocaethylene can substitute for cocaine in drug discrimination studies, and can produce stimulation of operant conditioning in rats. With regard to lethality, cocaethylene has been shown to be more potent than cocaine in mice and rats. The combination of cocaine and alcohol appears to exert more cardiovascular toxicity than either drug alone in humans. Alcohol appears to potentiate cocaine hepatotoxicity in both humans and mice.

  7. Memory and Brain Volume in Adults Prenatally Exposed to Alcohol

    Science.gov (United States)

    Coles, Claire D.; Goldstein, Felicia C.; Lynch, Mary Ellen; Chen, Xiangchuan; Kable, Julie A.; Johnson, Katrina C.; Hu, Xiaoping

    2011-01-01

    The impact of prenatal alcohol exposure on memory and brain development was investigated in 92 African-American, young adults who were first identified in the prenatal period. Three groups (Control, n = 26; Alcohol-related Neurodevelopmental Disorder, n = 36; and Dysmorphic, n = 30) were imaged using structural MRI with brain volume calculated for…

  8. Estimated Risk of Developing Selected DSM-IV Disorders among 5-Year-Old Children with Prenatal Cocaine Exposure

    Science.gov (United States)

    Morrow, Connie E.; Accornero, Veronica H.; Xue, Lihua; Manjunath, Sudha; Culbertson, Jan L.; Anthony, James C.; Bandstra, Emmalee S.

    2009-01-01

    We estimated childhood risk of developing selected DSM-IV Disorders, including Attention-Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), and Separation Anxiety Disorder (SAD), in children with prenatal cocaine exposure (PCE). Children were enrolled prospectively at birth (n = 476) with prenatal drug exposures documented…

  9. Longitudinal Study of Maternal Report of Sleep Problems in Children with Prenatal Exposure to Cocaine and Other Drugs

    Science.gov (United States)

    Stone, Kristen C.; High, Pamela C.; Miller-Loncar, Cynthia L.; LaGasse, Linda L.; Lester, Barry M.

    2009-01-01

    Sleep data were collected by maternal report in a prospective longitudinal follow-up of cocaine exposed and unexposed children. There were 139 subjects: 23 with no prenatal drug exposure, 55 exposed to cocaine alone or in combination with other drugs, and 61 exposed to drugs other than cocaine. Characteristics differed between exposure groups, including birth size, caretaker changes, and maternal SES and postnatal drug use. Compared to those with no drug exposure, children with prenatal drug exposure other than cocaine experienced greater sleep problems (mean [SD], 5 [4.93] vs 7.7 [4.85], p = .026). Prenatal nicotine exposure was a unique predictor of sleep problems (R2 = .028, p = .048). Early sleep problems predicted later sleep problems (all p’s <.01). Together, these preliminary findings suggest possible neurotoxic sleep effects that persist over time. Larger studies, however, need to be conducted that better control for potential postnatal confounding factors. PMID:19787489

  10. Longitudinal study of maternal report of sleep problems in children with prenatal exposure to cocaine and other drugs.

    Science.gov (United States)

    Stone, Kristen C; High, Pamela C; Miller-Loncar, Cynthia L; Lagasse, Linda L; Lester, Barry M

    2009-01-01

    Sleep data were collected by maternal report in a prospective longitudinal follow up of cocaine-exposed and unexposed children. There were 139 participants: 23 with no prenatal drug exposure, 55 exposed to cocaine alone or in combination with other drugs, and 61 exposed to drugs other than cocaine. Characteristics differed between exposure groups including birth size, caretaker changes, maternal socioeconomic status, and postnatal drug use. Compared to those with no drug exposure, children with prenatal drug exposure other than cocaine experienced greater sleep problems (p = .026). Prenatal nicotine exposure was a unique predictor of sleep problems (p = .048). Early sleep problems predicted later sleep problems (all ps effects that persist over time. Larger studies, however, need to be conducted that better control for potential postnatal confounding factors.

  11. The Relationship between Prenatal Care, Personal Alcohol Abuse and Alcohol Abuse in the Home Environment

    Science.gov (United States)

    Grekin, Emily R.; Ondersma, Steven J.

    2009-01-01

    Aims: Nearly one-fourth of African-American women receive no prenatal care during the first trimester of pregnancy. The aim of the current study is to identify factors that underlie inadequate prenatal care among African-American women. Maternal alcohol abuse has been examined as one risk factor for inadequate prenatal care, but findings have been…

  12. The Relationship between Prenatal Care, Personal Alcohol Abuse and Alcohol Abuse in the Home Environment

    Science.gov (United States)

    Grekin, Emily R.; Ondersma, Steven J.

    2009-01-01

    Aims: Nearly one-fourth of African-American women receive no prenatal care during the first trimester of pregnancy. The aim of the current study is to identify factors that underlie inadequate prenatal care among African-American women. Maternal alcohol abuse has been examined as one risk factor for inadequate prenatal care, but findings have been…

  13. Augmented D1 dopamine receptor signaling and immediate-early gene induction in adult striatum following prenatal cocaine

    Science.gov (United States)

    Tropea, Thomas F.; Guerriero, Réjean M.; Willuhn, Ingo; Unterwald, Ellen M.; Ehrlich, Michelle E.; Steiner, Heinz; Kosofsky, Barry E.

    2009-01-01

    Background Prenatal exposure to cocaine can impede normal brain development triggering a range of neuroanatomical and behavioral anomalies that are evident throughout life. Mouse models have been especially helpful in delineating neuro-teratogenic consequences following prenatal exposure tococaine. The present study employed a mouse model to investigate alterations in D1 dopamine receptor signaling and downstream immediate-early gene induction in the striatum of mice exposed to cocaine in utero. Methods Basal, forskolin- and D1 receptor agonist-induced cAMP levels were measured ex vivo in the adult male striatum in mice exposed to cocaine in utero. Further studies assessed cocaine-induced zif 268 and homer 1 expression in the striatum of juvenile (P15), adolescent (P36), and adult (P60) male mice. Results The D1 dopamine receptor agonist SKF82958 induced significantly higher levels of cAMP in adult male mice treated with cocaine in utero compared to saline controls. No effects of the prenatal treatment were found for cAMP formation induced by forskolin. Following an acute cocaine challenge (15 mg/kg, i.p.), these mice showed greater induction of zif 268 and homer 1, an effect that was most robust in the medial part of the mid-level striatum and became more pronounced with increasing age. Conclusions Together these findings indicate abnormally enhanced D1 receptor signal transduction in adult mice following prenatal cocaine exposure. Such changes in dopamine receptor signaling may underlie aspects of long-lasting neuro-teratogenic effects evident in some humans following in utero exposure to cocaine, and identify the striatum as one target potentially vulnerable to gestational cocaine exposure. PMID:18275938

  14. Prenatal cocaine exposure induces deficits in Pavlovian conditioning and sensory preconditioning among infant rat pups.

    Science.gov (United States)

    Heyser, C J; Chen, W J; Miller, J; Spear, N E; Spear, L P

    1990-12-01

    Offspring derived from Sprague-Dawley dams that received daily subcutaneous injection of 40 mg/kg.3 cc-1 cocaine hydrochloride (C40) or saline (LC) from Gestational Days 8-20 were tested for first-order Pavlovian conditioning and sensory preconditioning at Postnatal Days 8 (P8), P12, and P21. Although C40 dams gained significantly less weight than LC dams, pup body weights did not differ between the two groups. Significant sensory preconditioning was obtained at P8 and P12 (but not at P21) in LC offspring, confirming previous reports of decline in performance in this task during ontogeny. In contrast, C40 offspring failed to exhibit sensory preconditioning at any test age. In addition, C40 pups tested at P8 did not display significant first-order conditioning. Taken together these results suggest a more general deficit in cognitive functioning rather than a delay in cognitive development in prenatally cocaine-exposed offspring.

  15. Effects of Prenatal Alcohol Exposure and ADHD on Adaptive Functioning

    Science.gov (United States)

    Ware, Ashley L.; Glass, Leila; Crocker, Nicole; Deweese, Benjamin N.; Coles, Claire D.; Kable, Julie A.; May, Philip A.; Kalberg, Wendy O.; Sowell, Elizabeth R.; Jones, Kenneth Lyons; Riley, Edward P.; Mattson, Sarah N.

    2014-01-01

    Background Heavy prenatal alcohol exposure and attention-deficit/hyperactivity disorder (ADHD) are associated with adaptive behavior deficits. The present study examined the interaction between these two factors on parent ratings of adaptive behavior. Methods As part of a multisite study, primary caregivers of 317 children (8–16y, M=12.38) completed the Vineland Adaptive Behavior Scales-II (VABS-II). Four groups of subjects were included: children with prenatal alcohol exposure with (AE+, n = 82) and without ADHD (AE−, n = 34), children with ADHD (ADHD, n = 71), and control children (CON, n = 130). VABS-II domain scores (Communication, Daily Living Skills, Socialization) were examined using separate 2 (Alcohol Exposure [AE]) × 2 (ADHD diagnosis) between-subjects ANCOVAs. Results There were significant main effects of AE (p VABS-II domains; alcohol-exposed children had lower scores than children without prenatal alcohol exposure and children with ADHD had lower scores than those without ADHD. There was a significant AE × ADHD interaction effect for Communication [F (1, 308) = 7.49, p = .007, partial η2 =.024], but not Daily Living Skills or Socialization domains (ps > .27). Follow up analyses in the Communication domain indicated the effects of ADHD were stronger in comparison subjects (ADHD vs. CON) than exposed subjects (AE+ vs. AE−) and the effects of alcohol exposure were stronger in subjects without ADHD (AE− vs. CON) than in subjects with ADHD (AE+ vs. ADHD). Conclusion As found previously, both prenatal alcohol exposure and ADHD increase adaptive behavior deficits in all domains. However, these two factors interact to cause the greatest impairment in children with both prenatal alcohol exposure and ADHD for communication abilities. These results further demonstrate the deleterious effects of prenatal alcohol exposure and broadens our understanding of how ADHD exacerbates behavioral outcomes in this population. PMID:24655090

  16. Comparative study of the phonology of preschool children prenatally exposed to cocaine and multiple drugs and non-exposed children.

    Science.gov (United States)

    Madison, C L; Johnson, J M; Seikel, J A; Arnold, M; Schultheis, L

    1998-01-01

    Cocaine and multiple drug abuse among young adults has spawned research interest in fetal exposure and the sequela of that exposure during the formative developmental years. Previous study of the language development of exposed children has not specifically addressed phonological acquisition. In the present study, the speech of 25 children prenatally exposed to cocaine and multiple drugs was analyzed and compared to that of 25 children who were not prenatally exposed to determine if differences were evident in their phonological patterns. The children ranged in age from 22 months to 51 months. The number and type of phonological processes produced, number of utterances needed to produce a 50-word sample, number of unintelligible words produced, and Home Observation for Measurement of the Environment (HOME) scores were recorded and analyzed. The use of cocaine and multiple drugs during pregnancy was associated with an increase in the use of phonological processes.

  17. Cocaine

    Science.gov (United States)

    Cocaine is a white powder. It can be snorted up the nose or mixed with water and injected with a needle. Cocaine can also be made into small white rocks, ... Crack is smoked in a small glass pipe. Cocaine speeds up your whole body. You may feel ...

  18. Cocaine

    Science.gov (United States)

    ... nerves, including seizures and strokes. How can a cocaine overdose be treated? Because cocaine overdose often leads to a heart attack, stroke, or ... severe paranoia with auditory hallucinations A person can overdose on cocaine, which can lead to death. Behavioral therapy may ...

  19. Prenatal Alcohol Exposure Selectively Enhances Young Adult Perceived Pleasantness of Alcohol Odors

    Science.gov (United States)

    Hannigan, John H.; Chiodo, Lisa M.; Sokol, Robert J.; Janisse, James; Delaney-Black, Virginia

    2015-01-01

    Prenatal Alcohol Exposure (PAE) can lead to life-long neurobehavioral and social problems that can include a greater likelihood of early use and/or abuse of alcohol compared to older teens and young adults without PAE. Basic research in animals demonstrates that PAE influences later postnatal responses to chemosensory cues (i.e., odor & taste) associated with alcohol. We hypothesized that PAE would be related to poorer abilities to identify odors of alcohol-containing beverages, and would alter perceived alcohol odor intensity and pleasantness. To address this hypothesis we examined responses to alcohol and other odors in a small sample of young adults with detailed prenatal histories of exposure to alcohol and other drugs. The key finding from our controlled analyses is that higher levels of PAE were related to higher relative ratings of pleasantness for alcohol odors. As far as we are aware, this is the first published study to report the influence of PAE on responses to alcohol beverage odors in young adults. These findings are consistent with the hypothesis that positive associations (i.e., “pleasantness”) to the chemosensory properties of alcohol (i.e., odor) are acquired prenatally and are retained for many years despite myriad interceding postnatal experiences. Alternate hypotheses may also be supported by the results. There are potential implications of altered alcohol odor responses for understanding individual differences in initiation of drinking, and alcohol seeking and high-risk alcohol-related behaviors in young adults. PMID:25600468

  20. Prenatal cocaine exposure impairs cognitive function of progeny via insulin growth factor II epigenetic regulation.

    Science.gov (United States)

    Zhao, Qian; Hou, Jing; Chen, Bo; Shao, Xue; Zhu, Ruiming; Bu, Qian; Gu, Hui; Li, Yan; Zhang, Baolai; Du, Changman; Fu, Dengqi; Kong, Jueying; Luo, Li; Long, Hailei; Li, Hongyu; Deng, Yi; Zhao, Yinglan; Cen, Xiaobo

    2015-10-01

    Studies have showed that prenatal cocaine exposure (PCOC) can impair cognitive function and social behavior of the offspring; however, the mechanism underlying such effect is poorly understood. Insulin-like growth factor II (Igf-II), an imprinted gene, has a critical role in memory consolidation and enhancement. We hypothesized that epigenetic regulation of hippocampal Igf-II may attribute to the cognitive deficits of PCOC offspring. We used Morris water maze and open-field task to test the cognitive function in PCOC offspring. The epigenetic alteration involved in hippocampal Igf-II expression deficit in PCOC offspring was studied by determining Igf-II methylation status, DNA methyltransferases (DNMT) expressions and L-methionine level. Moreover, IGF-II rescue experiments were performed and the downstream signalings were investigated in PCOC offspring. In behavioral tests, we observed impaired spatial learning and memory and increased anxiety in PCOC offspring; moreover, hippocampal IGF-II mRNA and protein expressions were significantly decreased. Hippocampal methylation of cytosine-phospho-guanine (CpG) dinucleotides in differentially methylated region (DMR) 2 of Igf-II was elevated in PCOC offspring, which may be driven by the upregulation of L-methionine and DNA methyltransferase (DNMT) 1. Importantly, intra-hippocampal injection of recombinant IGF-II reactivated the repressed calcium calmodulin kinase II α (CaMKIIα) and reversed cognitive deficits in PCOC offspring. Collectively, our findings suggest that cocaine exposure during pregnancy impairs cognitive function of offspring through epigenetic modification of Igf-II gene. Enhancing IGF-II signaling may represent a novel therapeutical strategy for cocaine-induced cognitive impairment.

  1. Structural Brain Imaging in Children and Adolescents Following Prenatal Cocaine Exposure

    Science.gov (United States)

    Akyuz, Nurunisa; Kekatpure, Minal V.; Liu, Jie; Sheinkopf, Stephen J.; Quinn, Brian T.; Lala, Meenakshi D.; Kennedy, David; Makris, Nikos; Lester, Barry M.; Kosofsky, Barry E.

    2014-01-01

    Brain morphometry of 21 children, who were followed from birth and underwent structural brain magnetic resonance imaging (MRI) at 8–10 years, were studied. This cohort included 11 children with prenatal cocaine exposure (CE) and 10 non-cocaine exposed children (NCE). We compared the CE versus NCE groups using FreeSurfer to automatically segment and quantify the volume of individual brain structures. In addition, we created a pediatric atlas specifically for this population and demonstrate the enhanced accuracy of this approach. We found an overall trend towards smaller brain volumes among CE children. The volume differences were significant for cortical gray matter, thalamus and putamen. Here, reductions in thalamic and putaminal volumes showed a robust inverse-correlation with exposure levels, thus highlighting effects on dopamine rich brain regions that form key components of brain circuitry known to play important roles in behavior and attention. Interestingly, head circumferences (HCs) at birth as well as at the time of imaging showed a tendency for smaller size among CE children. HCs at the time of imaging correlated well with the cortical volumes, for all subjects. In contrast, HCs at birth were predictive of the cortical volume only for the CE group. A subgroup of these subjects (6 CE and 4 NCE) was also scanned at 13–15 years old. In subjects who were scanned twice, we found that the trend for smaller structures continues into 13–15 years of age. We found that the differences in structural volumes between CE and NCE groups are largely diminished when the HCs are matched by study design or controlled for. Participants in this study were drawn from a unique longitudinal cohort, and while the small sample size precludes strong conclusions, the results point to reductions in HCs and in specific brain structures that persist through teenage years in children who were exposed to cocaine in utero. PMID:24994509

  2. Prenatal cocaine exposure: the role of cumulative environmental risk and maternal harshness in the development of child internalizing behavior problems in kindergarten.

    Science.gov (United States)

    Eiden, Rina D; Godleski, Stephanie; Colder, Craig R; Schuetze, Pamela

    2014-01-01

    This study examined the associations between prenatal exposure to cocaine and other substances and child internalizing behavior problems at kindergarten. We investigated whether maternal harshness or cumulative environmental risk mediated or moderated this association. Participants consisted of 216 (116 cocaine exposed, 100 non-cocaine exposed) mother-infant dyads participating in an ongoing longitudinal study of prenatal cocaine exposure. Results indicated that, as hypothesized, maternal harshness moderated the association between prenatal cocaine exposure to child internalizing in kindergarten such that prenatal cocaine exposure increased risk for internalizing problems at high levels of maternal harshness from 7 to 36months and decreased risk at low levels of harshness. Contrary to hypothesis, the association between prenatal cocaine exposure and child internalizing in kindergarten was not mediated by maternal harshness or cumulative environmental risk. However, cumulative environmental risk (from 1month of child age to kindergarten) was predictive of child internalizing behavior problems at kindergarten. Results have implications for parenting interventions that may be targeted toward reducing maternal harshness in high risk samples characterized by maternal substance use in pregnancy.

  3. Cocaine enhances resistance to extinction of responding for brain-stimulation reward in adult prenatally stressed rats.

    Science.gov (United States)

    Gao, Shuibo; Suenaga, Toshiko; Oki, Yutaka; Yukie, Masao; Nakahara, Daiichiro

    2011-10-01

    The present experiment assessed whether prenatal stress (PS) can alter the ability of acute and chronic cocaine administration to increase and decrease the rewarding effectiveness of the medial forebrain bundle (MFB) using intracranial self-stimulation (ICSS), and also whether PS can affect the extinction of the MFB stimulation response. Adult male offspring of female rats that received PS or no PS (nPS) were implanted with MFB stimulating electrodes, and were then tested in ICSS paradigms. In both nPS and PS offspring, acute cocaine injection decreased ICSS thresholds dose-dependently. However, the threshold-lowering effects at any dose were not significantly different between groups. There was also no group-difference in the threshold-elevating effects of chronic cocaine administration. Nevertheless, chronically drug-administered PS rats exhibited a resistance to the extinguishing of the response for brain-stimulation reward when acutely treated with cocaine, as compared to extinction without cocaine treatment. The results suggest that PS may weaken the ability for response inhibition under cocaine loading in male adult offspring.

  4. Beneficial effects of the sigma1 receptor agonists igmesine and dehydroepiandrosterone against learning impairments in rats prenatally exposed to cocaine.

    Science.gov (United States)

    Meunier, Johann; Maurice, Tangui

    2004-01-01

    In utero cocaine (IUC) exposure results in offspring rats in complex neurochemical and behavioral alterations, particularly affecting learning and memory processes. We examined here the impact of IUC exposure on memory functions in male and female offspring rats and report that selective sigma(1) (sigma(1)) receptor agonists are effective in reversing the deficits. Dams received a daily cocaine, 20 mg/kg ip, injection between gestational days E17 to E20. Learning was examined in offspring between day P30 and P41 using delayed alternation in the T-maze, water-maze learning and passive avoidance. Both male and female rats prenatally exposed to cocaine showed delayed alternation deficits and impairments of acquisition of a fixed platform position in the water maze, as shown by higher acquisition latencies and diminutions of time spent in the training quadrant during the probe test. The acquisition of a daily changing platform position also demonstrated impaired working memory. Finally, passive avoidance deficits were observed. Pretreatment with the synthetic sigma(1) agonist igmesine (0.1-1 mg/kg ip) or the neuroactive steroid dehydroepiandrosterone (DHEA 10-40 mg/kg ip) reversed the prenatal cocaine-induced learning deficits in offspring rats for each test. The sigma(1) antagonist BD1063 (1 mg/kg ip) failed to affect performances alone but blocked the igmesine and DHEA effects, confirming the involvement of the sigma(1) receptor. IUC exposure thus results in marked memory deficits, affecting spatial and nonspatial short- and long-term memories in juvenile male and female offspring rats. The activation of the sigma(1) neuromodulatory receptor allows a complete behavioral recovery of the memory functions in prenatally cocaine-exposed rats.

  5. Sensory Processing Disorder in a Primate Model: Evidence from a Longitudinal Study of Prenatal Alcohol and Prenatal Stress Effects

    Science.gov (United States)

    Schneider, Mary L.; Moore, Colleen F.; Gajewski, Lisa L.; Larson, Julie A.; Roberts, Andrew D.; Converse, Alexander K.; DeJesus, Onofre T.

    2008-01-01

    Disrupted sensory processing, characterized by over- or underresponsiveness to environmental stimuli, has been reported in children with a variety of developmental disabilities. This study examined the effects of prenatal stress and moderate-level prenatal alcohol exposure on tactile sensitivity and its relationship to striatal dopamine system…

  6. Biomarkers for the detection of prenatal alcohol exposure (PAE)

    DEFF Research Database (Denmark)

    Bjerregaard, Lene Berit Skov; Bager, Heidi; Husby, Steffen

    2017-01-01

    Alcohol exposure during pregnancy can cause adverse effects to the fetus, because it interferes with fetal development, leading to later physical and mental impairment. The most common clinical tool to determine fetal alcohol exposure is maternal self-reporting. However, a more objective and useful...... method is based on the use of biomarkers in biological specimens alone or in combination with maternal self-reporting. This review reports on clinically relevant biomarkers for detection of prenatal alcohol exposure (PAE). A systematic search was performed to ensure a proper overview in existing...... literature. Studies were selected to give an overview on clinically relevant neonatal and maternal biomarkers. The direct biomarkers fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG), ethyl sulfate, and phosphatidylethanol (PEth) were found to be the most appropriate biomarkers in relation...

  7. Alcohol and cocaine co-consumption in two European cities assessed by wastewater analysis.

    Science.gov (United States)

    Rodríguez-Álvarez, Tania; Racamonde, Inés; González-Mariño, Iria; Borsotti, Andrea; Rodil, Rosario; Rodríguez, Isaac; Zuccato, Ettore; Quintana, José Benito; Castiglioni, Sara

    2015-12-01

    The quantitative determination of urinary biomarkers in raw wastewater has emerged in recent years as a promising tool for estimating the consumption of illicit drugs, tobacco and alcohol in a population and for comparing local and temporal trends. In this study, a three-year monitoring campaign (2012-2014) was conducted to compare alcohol and cocaine use in two European cities (Santiago de Compostela, Spain, and Milan, Italy) by wastewater analysis. Ethyl sulphate and benzoylecgonine were used, respectively, as biomarkers of ethanol and cocaine consumption and cocaethylene as an indicator of co-consumption of both substances. Biomarkers were measured using liquid chromatography-tandem mass spectrometry and concentrations were converted to rates of consumption using specific correction factors. Results were statistically compared in terms of geographic and temporal tendencies. Alcohol intake was significantly higher in Santiago than in Milan (13.6L versus 5.1L ethanol/1000 people day, averages). Cocaine use was higher in Milan than in Santiago de Compostela (800 versus 632 mg/1000 people day, averages). A significant higher consumption of both alcohol and cocaine was observed during the weekends (~23-75% more than on weekdays) in both cities. In terms of years, slight changes were observed, but no clear trends as representative of the whole year could be identified because of the limited number of days sampled. Co-consumption was evaluated using the cocaethylene/benzoylecgonine ratio, which was higher during the weekend in both cities (58% in Santiago and 47% in Milan over the non-weekend day means), indicating a greater co-consumption when cocaine is used as a recreational drug. Wastewater-based epidemiology gave estimates of alcohol and cocaine use in agreement with previous wastewater studies and with recent European surveillance and prevalence data, and weekly profiles of use and preferential patterns of consumption could be plot.

  8. Prenatal Alcohol Exposure Is Associated with Conduct Disorder in Adolescence: Findings from a Birth Cohort

    Science.gov (United States)

    Larkby, Cynthia A.; Goldschmidt, Lidush; Hanusa, Barbara H.; Day, Nancy L.

    2011-01-01

    Objective: To evaluate the association between prenatal alcohol exposure and the rate of conduct disorder in exposed compared with unexposed adolescents. Method: Data for these analyses are from a longitudinal study of prenatal substance exposures. Women were interviewed at their fourth and seventh prenatal months, and with their children, at…

  9. Effects of Prenatal Alcohol Exposure on the Developing Kidneys

    Directory of Open Access Journals (Sweden)

    Farahnak Assadi

    2008-04-01

    Full Text Available Objective: Clinical and experimental studies strongly suggest that prenatal alcohol exposure is associated with zinc deficiency and impaired renal tubular function. Whether maternal alcohol consumption during pregnancy causes renal tubular cell injury is unknown.Material & Methods: Renal function was studied in 8 infants with fetal alcohol syndrome (FAS and 8 healthy age-matched infants. Renal function and structure were also examined in 11 offspring of rats exposed to alcohol during gestation.Findings: Infants with FAS had limited ability to concentrate urine after water restriction (P<0.001 and impaired acidification after acute acid loading (P<0.001 compared to control group. Plasma zinc levels were lower (P<0.001 and urinary zinc excretion was higher (P<0.001 in infants with FAS compared to control infants. Scanning electron microscopic studies revealed cytoplasmic mitochondrial hypertrophy and vacuolar structures of the epithelial cells of the cortical collecting ducts in the rat kidney following fetal exposure to alcohol.Conclusion: These findings suggest that offspring of rats exposed to alcohol during fetal life have renal functional and structural abnormalities that may be responsible in the genesis of renal functional abnormalities as described in infants with FAS.

  10. Estimated Risk of Developing Selected DSM-IV Disorders Among 5-Year-Old Children with Prenatal Cocaine Exposure

    Science.gov (United States)

    Morrow, Connie E.; Xue, Lihua; Manjunath, Sudha; Culbertson, Jan C.; Accornero, Veronica H.; Anthony, James C.; Bandstra, Emmalee S.

    2016-01-01

    This study estimated childhood risk of developing selected DSM-IV Disorders, including Attention-Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), and Separation Anxiety Disorder (SAD), in children with prenatal cocaine exposure (PCE). Children were enrolled prospectively at birth (n=476) with prenatal drug exposures documented by maternal interview, urine and meconium assays. Study participants included 400 African-American children from the birth cohort, 208 cocaine-exposed (CE) and 192 non-cocaine-exposed (NCE) who attended a 5-year follow-up assessment and whose caregiver completed the Computerized Diagnostic Interview Schedule for Children. Under a generalized linear model (logistic link), Fisher’s exact methods were used to estimate the CE-associated relative risk (RR) of these disorders. Results indicated a modest but statistically robust elevation of ADHD risk associated with increasing levels of PCE (pEstimated cumulative incidence proportions among CE children were 2.9% for ADHD (vs 3.1% NCE); 1.4% for SAD (vs 1.6% NCE); and 4.3% for ODD (vs 6.8% NCE). Findings offer suggestive evidence of increased risk of ADHD (but not ODD or SAD) in relation to an increasing gradient of PCE during gestation.

  11. Identification of alcohol and cocaine derivatives in pregnacy in meconium samples.

    Directory of Open Access Journals (Sweden)

    Mario Moraes Castro

    2014-12-01

    The investigation consisted on an observational analytic cross-sectional study of 240 puerperal women and their children born at the Hospital Pereira Rossell from November 2010 to March 2011. The method used for the identification of free fatty acid ethyl esters in meconium of newborns was developed at the Polo Tecnológico de Pando, Facultad de Química, Universidad de la República for this investigation. The media of maternal age was 25; Alcohol consumption during pregnancy was admitted by 81 women, and the presence of free fatty acids ethyl esters was confirmed in 113 cases (49.78%; the consumption of cocaine hydrochloride and freebase cocaine was positive in 9.25% cases. Alcohol consumption was identified in half of pregnant women. The consumption of cocaine derivatives in the population studied was high. Exposed fetus can be identified with the analysis of meconium samples, with more certainty than by reports of patients.

  12. Neurobiology and Neurodevelopmental Impact of Childhood Traumatic Stress and Prenatal Alcohol Exposure

    Science.gov (United States)

    Henry, Jim; Sloane, Mark; Black-Pond, Connie

    2007-01-01

    Purpose: Research reveals that prenatal alcohol exposure and child trauma (i.e., abuse, neglect, sexual abuse) can have deleterious effects on child development across multiple domains. This study analyzed the impact on childhood neurodevelopment of prenatal alcohol exposure and postnatal traumatic experience compared to postnatal traumatic…

  13. Social Information Processing Skills in Children with Histories of Heavy Prenatal Alcohol Exposure

    Science.gov (United States)

    McGee, Christie L.; Bjorkquist, Olivia A.; Price, Joseph M.; Mattson, Sarah N.; Riley, Edward P.

    2009-01-01

    Based on caregiver report, children with prenatal alcohol exposure have difficulty with social functioning, but little is known about their social cognition. The current study assessed the social information processing patterns of school-age children with heavy prenatal alcohol exposure using a paradigm based on Crick and Dodge's reformulated…

  14. Nuclear changes in oral mucosa of alcoholics and crack cocaine users.

    Science.gov (United States)

    Webber, L P; Pellicioli, A C A; Magnusson, A S; Danilevicz, C K; Bueno, C C; Sant'Ana Filho, M; Rados, P V; Carrard, V C

    2016-02-01

    The effects of drugs of abuse on oral mucosa are only partly understood. The aims of the present study were to: (1) evaluate the frequency of nuclear changes in normal-appearing oral mucosa of alcoholics and crack cocaine users and (2) assess their association with cell proliferation rate. Oral smears were obtained from the border of the tongue and floor of the mouth of 26 crack cocaine users (24 males and 2 females), 29 alcoholics (17 males and 12 females), and 35 controls (17 males and 18 females). Histological slides were submitted to Feulgen staining to assess the frequency of micronuclei (MN), binucleated cells (BN), broken eggs (BE), and karyorrhexis (KR). A significant increase in the frequency of MN was observed in cells exfoliated from the tongue of crack cocaine users (p = 0.01), and alcoholics showed a higher frequency of KR in cells obtained from the floor of the mouth (p = 0.01). Our findings suggest that the use of crack cocaine induces clastogenic effects, whereas alcoholism is associated with higher degrees of keratinization in the floor of the mouth.

  15. Longitudinal changes of amygdala and default mode activation in adolescents prenatally exposed to cocaine.

    Science.gov (United States)

    Li, Zhihao; Coles, Claire D; Lynch, Mary Ellen; Luo, Yuejia; Hu, Xiaoping

    2016-01-01

    Prenatal cocaine exposure (PCE) is associated with long-term and negative effect on arousal regulation. Recent neuroimaging studies have examined brain mechanisms related to arousal dysregulation with cross-sectional experimental designs; but longitudinal changes in the brain, reflecting group differences in neurodevelopment, have never been directly examined. To directly assess the interaction of PCE and neurodevelopment, the present study used a longitudinal design to analyze functional magnetic resonance imaging (fMRI) data collected from 33 adolescents (21 with PCE and 12 non-exposed controls) while they performed the same working memory task with emotional distracters at two points in time. The mean age of participants was 14.3 years at time_1 and 16.7 years at time_2. With confounding factors statistically controlled, the fMRI data revealed significant exposure-by-time interaction in the activations of the amygdala and default mode network (DMN). For the control adolescents, brain activations associated with emotional arousal (amygdala) and cognitive effort (DMN) were both reduced at time_2 as compared to that at time_1. However, these activation reductions were not observed in the PCE group, indicating persistently high levels of emotional arousal and cognitive effort. In addition, correlations between longitudinal changes in the brain and in behavior have shown that adolescents with persistently high emotional arousal were more likely in need of high cognitive effort; and their cognitive performance was more likely to be affected by distractive challenges. The present results complement and extend previous findings from cross-sectional studies with further evidence supporting the view of PCE associated long-term teratogenic effects on arousal regulation.

  16. Preadolescent behavior problems after prenatal cocaine exposure: Relationship between teacher and caretaker ratings (Maternal Lifestyle Study)

    Science.gov (United States)

    Bada, Henrietta S.; Bann, Carla; Bauer, Charles R.; Shankaran, Seetha; Lester, Barry; LaGasse, Linda; Hammond, Jane; Whitaker, Toni; Das, Abhik; Tan, Sylvia; Higgins, Rosemary

    2010-01-01

    Background We previously reported an association between prenatal cocaine exposure (PCE) and childhood behavior problems as observed by the parent or caretaker. However, these behavior problems may not manifest in a structured environment, such as a school setting. Objective We determined whether there is an association between PCE and school behavior problems and whether ratings of behavior problems from the teacher differ from those noted by the parent or caretaker. Methods The Maternal Lifestyle Study, a multicenter study, enrolled 1388 children with and without PCE at one month of age for longitudinal assessment. Teachers masked to prenatal drug exposure status completed the Teacher Report Form (TRF/6-18) when children were 7, 9, and 11 years old. We also administered the Child Behavior Checklist-parent report (CBCL) to the parent/caretaker at same ages and then at 13 years. We performed latent growth curve modeling to determine whether high PCE will predict externalizing, internalizing, total behavior, and attention problems at 7 years of age and whether changes in problems' scores over time differ between those exposed and non-exposed from both teacher and parent report. Besides levels of PCE as predictors, we controlled for the following covariates, namely: site, child characteristics (gender and other prenatal drug exposures), family level influences (maternal age, depression and psychological symptomatology, continuing drug use, exposure to domestic violence, home environment, and socioeconomic status), and community level factors (neighborhood and community violence). Results The mean behavior problem T scores from the teacher report were significantly higher than ratings by the parent or caretaker. Latent growth curve modeling revealed a significant relationship between intercepts of problem T scores from teacher and parent ratings; i.e., children that were rated poorly by teachers were also rated poorly by their parent/caretaker or vice versa. After

  17. Attachment Status in Children Prenatally Exposed to Cocaine and Other Substances

    Science.gov (United States)

    Seifer, Ronald; LaGasse, Linda L.; Lester, Barry; Bauer, Charles R.; Shankaran, Seetha; Bada, Henrietta S.; Wright, Linda L.; Smeriglio, Vincent L.; Liu, Jing

    2004-01-01

    Attachment status of children exposed in utero to cocaine, opiates, and other substances was examined at 18 months (n=860) and 36 months (n=732) corrected age. Children exposed to cocaine and opiates had slightly lower rates of attachment security (but not disorganization), and their insecurity was skewed toward ambivalent, rather than avoidant,…

  18. Mitigating the Effects of Poverty and Crime: The Long-Term Effects of an Early Intervention Programme for Children Who Were Developmentally Delayed and Prenatally Exposed to Cocaine

    Science.gov (United States)

    Ullery, Mary Anne; Gonzalez, Antonio; Katz, Lynne

    2016-01-01

    This study explores the long-term impact on participation in the Linda Ray Intervention Program (LRIP) for children (n = 54) who were developmentally delayed and prenatally exposed to cocaine. By identifying a group of programme graduates from a high crime/high poverty neighbourhood in Miami-Dade County using ArcGIS 10.2 software, a…

  19. Comparison of 12-Year-Old Children with Prenatal Exposure to Cocaine and Non-Exposed Controls on Caregiver Ratings of Executive Function

    Science.gov (United States)

    Minnes, Sonia; Singer, Lynn; Min, Meeyoung O.; Lang, Adelaide M.; Ben-Harush, Aya; Short, Elizabeth; Wu, Miaoping

    2013-01-01

    Differences in caregiver reported executive function in 12-year-old children who were prenatally exposed to cocaine (PCE) compared to children who were not prenatally exposed to cocaine (NCE) were assessed. One hundred and sixty-nine PCE and 169 NCE, primarily African-American, low socioeconomic status children participated in a prospective longitudinal study. The Behavior Rating Inventory of Executive Function (BRIEF) Parent Form was administered. Two broadband BRIEF scores (Behavioral Regulation Index (BRI) and Metacognition Index (MI)) and a summary Global Executive Composite (GEC) were computed. Multiple and logistic regression analyses were used to assess the effects of amount of PCE on executive function, controlling for covariates including caregiver (rater) psychological distress, child’s gender and other prenatal drug exposure variables. After adjustment for covariates, amount of PCE was associated with the GEC and two MI subscales, Plan/Organize and Monitor, with heavier exposure associated with more problems of executive function. An amount of PCE by gender interaction revealed amount of PCE effects in other remaining subscales of the MI (Initiate, Working Memory, and Organization of Materials) only among girls. Head circumference did not mediate the effects of cocaine on outcomes. Higher current caregiver psychological distress levels were independently associated with poorer ratings on the executive function scales. Assessment and targeted interventions to improve metacognitive processes are recommended for girls who were prenatally exposed to cocaine. PMID:23423839

  20. Accumbal FosB/DeltaFosB immunoreactivity and conditioned place preference in alcohol-preferring AA rats and alcohol-avoiding ANA rats treated repeatedly with cocaine.

    Science.gov (United States)

    Marttila, Kristiina; Petteri Piepponen, T; Kiianmaa, Kalervo; Ahtee, Liisa

    2007-07-30

    Transcription factor DeltaFosB has been implicated in the psychomotor responses and rewarding effects of drugs of abuse. In the present study, we compared the effects of cocaine on the expression of DeltaFosB-like proteins by immunohistochemistry in striatal brain areas of alcohol-preferring (AA) and alcohol-avoiding (ANA) rats. Cocaine was administered using a previously verified treatment paradigm that sensitized the locomotor response to cocaine in AA but not in ANA rats. We also studied the rewarding effects of cocaine with a conditioned place preference (CPP) paradigm in both lines of rats. Cocaine treatment increased the FosB/DeltaFosB immunoreactivity (IR) in the nucleus accumbens of AA rats but not in ANA rats. In addition, after repeated saline injections the accumbal FosB/DeltaFosB IR was significantly greater in saline-injected AA rats than in ANA rats. In the caudate-putamen cocaine significantly increased FosB/DeltaFosB IR, but no differences were found between the rats of two lines. In the CPP experiment, AA rats treated with cocaine 2.5 mg/kg preferred the cocaine-associated compartment, in contrast to ANA rats, which did not show such a preference. In conclusion, our findings show that AA rats are more sensitive to cocaine than ANA rats, and suggest that one possible mediator for this increased sensitivity could be the increased expression of fosB-derived proteins in the nucleus accumbens of AA rats.

  1. Prenatal Substance Exposure: Neurobiological Organization at One Month

    Science.gov (United States)

    Conradt, Elisabeth; Sheinkopf, Stephen J.; Lester, Barry M.; Tronick, Ed; Lagasse, Linda L.; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles R.; Whitaker, Toni M.; Hammond, Jane A.

    2013-01-01

    Objective To examine the autonomic nervous system and neurobehavioral response to a sustained visual attention challenge among 1-month old infants with prenatal substance exposure. Study design We measured heart rate (HR), respiratory sinus arrhythmia (RSA), and neurobehavior during sustained visual orientation tasks included in the NICU Network Neurobehavioral Scale (NNNS) in 1,129, 1-month infants with prenatal substance exposure. Four groups were compared: infants with prenatal cocaine and opiate exposure, infants with cocaine exposure, infants with opiate exposure, and infants with exposure to other substances (i.e. alcohol, marijuana, and tobacco). Results Infants with prenatal cocaine and opiate exposure had the highest HRs and lowest levels of RSA during a sustained visual attention procedure compared with the other three groups. Infants with prenatal cocaine and opiate exposure had poorer quality of movement and more hypertonicity during the NNNS exam compared with the other three exposure groups. Infants with prenatal cocaine and opiate exposure had more nonoptimal reflexes and stress/abstinence signs compared with infants with prenatal cocaine exposure only and infants with prenatal exposure to alcohol, tobacco, and marijuana. Conclusions Problems with arousal regulation were identified among infants with prenatal substance exposure. Autonomic dysregulation has been implicated as a mechanism by which these difficulties occur. Our results suggest that infants with both prenatal cocaine and opiate exposure have the greatest autonomic response to the challenge of a sustained visual attention task, which may place these infants at risk for developing problems associated with physiological and behavioral regulation, a necessary prerequisite for early learning. PMID:23743094

  2. Epigenetic modulation of brain gene networks for cocaine and alcohol abuse.

    Science.gov (United States)

    Farris, Sean P; Harris, Robert A; Ponomarev, Igor

    2015-01-01

    Cocaine and alcohol are two substances of abuse that prominently affect the central nervous system (CNS). Repeated exposure to cocaine and alcohol leads to longstanding changes in gene expression, and subsequent functional CNS plasticity, throughout multiple brain regions. Epigenetic modifications of histones are one proposed mechanism guiding these enduring changes to the transcriptome. Characterizing the large number of available biological relationships as network models can reveal unexpected biochemical relationships. Clustering analysis of variation from whole-genome sequencing of gene expression (RNA-Seq) and histone H3 lysine 4 trimethylation (H3K4me3) events (ChIP-Seq) revealed the underlying structure of the transcriptional and epigenomic landscape within hippocampal postmortem brain tissue of drug abusers and control cases. Distinct sets of interrelated networks for cocaine and alcohol abuse were determined for each abusive substance. The network approach identified subsets of functionally related genes that are regulated in agreement with H3K4me3 changes, suggesting cause and effect relationships between this epigenetic mark and gene expression. Gene expression networks consisted of recognized substrates for addiction, such as the dopamine- and cAMP-regulated neuronal phosphoprotein PPP1R1B/DARPP-32 and the vesicular glutamate transporter SLC17A7/VGLUT1 as well as potentially novel molecular targets for substance abuse. Through a systems biology based approach our results illustrate the utility of integrating epigenetic and transcript expression to establish relevant biological networks in the human brain for addiction. Future work with laboratory models may clarify the functional relevance of these gene networks for cocaine and alcohol, and provide a framework for the development of medications for the treatment of addiction.

  3. Epigenetic Modulation of Brain Gene Networks for Cocaine and Alcohol Abuse

    Directory of Open Access Journals (Sweden)

    Sean P Farris

    2015-05-01

    Full Text Available Cocaine and alcohol are two substances of abuse that prominently affect the central nervous system (CNS. Repeated exposure to cocaine and alcohol leads to longstanding changes in gene expression, and subsequent functional CNS plasticity, throughout multiple brain regions. Epigenetic modifications of histones are one proposed mechanism guiding these enduring changes to the transcriptome. Characterizing the large number of available biological relationships as network models can reveal unexpected biochemical relationships. Clustering analysis of variation from whole-genome sequencing of gene expression (RNA-Seq and histone H3 lysine 4 trimethylation (H3K4me3 events (ChIP-Seq revealed the underlying structure of the transcriptional and epigenomic landscape within hippocampal postmortem brain tissue of drug abusers and control cases. Distinct sets of interrelated networks for cocaine and alcohol abuse were determined for each abusive substance. The network approach identified subsets of functionally related genes that are regulated in agreement with H3K4me3 changes, suggesting cause and effect relationships between this epigenetic mark and gene expression. Gene expression networks consisted of recognized substrates for addiction, such as the dopamine- and cAMP-regulated neuronal phosphoprotein PPP1R1B / DARPP-32 and the vesicular glutamate transporter SLC17A7 / VGLUT1 as well as potentially novel molecular targets for substance abuse. Through a systems biology based approach our results illustrate the utility of integrating epigenetic and transcript expression to establish relevant biological networks in the human brain for addiction. Future work with laboratory models may clarify the functional relevance of these gene networks for cocaine and alcohol, and provide a framework for the development of medications for the treatment of addiction.

  4. Effects of prenatal alcohol exposure and attention-deficit/hyperactivity disorder on adaptive functioning.

    Science.gov (United States)

    Ware, Ashley L; Glass, Leila; Crocker, Nicole; Deweese, Benjamin N; Coles, Claire D; Kable, Julie A; May, Philip A; Kalberg, Wendy O; Sowell, Elizabeth R; Jones, Kenneth L; Riley, Edward P; Mattson, Sarah N

    2014-05-01

    Heavy prenatal alcohol exposure and attention-deficit/hyperactivity disorder (ADHD) are associated with adaptive behavior deficits. This study examined the interaction between these 2 factors on parent ratings of adaptive behavior. As part of a multisite study, primary caregivers of 317 children (8 to 16 years, M = 12.38) completed the Vineland Adaptive Behavior Scales-Second Edition (VABS-II). Four groups of subjects were included: children with prenatal alcohol exposure with ADHD (AE+, n = 82), children with prenatal alcohol exposure without ADHD (AE-, n = 34), children with ADHD (ADHD, n = 71), and control children (CON, n = 130). VABS-II domain scores (Communication, Daily Living Skills, Socialization) were examined using separate 2 (Alcohol Exposure [AE]) × 2 (ADHD diagnosis) between-subjects analyses of covariance. There were significant main effects of AE (p VABS-II domains; alcohol-exposed children had lower scores than children without prenatal alcohol exposure and children with ADHD had lower scores than those without ADHD. There was a significant AE × ADHD interaction effect for Communication, F(1, 308) = 7.49, p = 0.007, partial η(2) = 0.024, but not Daily Living Skills or Socialization domains (ps > 0.27). Follow-up analyses in the Communication domain indicated the effects of ADHD were stronger in comparison subjects (ADHD vs. CON) than exposed subjects (AE+ vs. AE-), and the effects of alcohol exposure were stronger in subjects without ADHD (AE- vs. CON) than in subjects with ADHD (AE+ vs. As found previously, both prenatal alcohol exposure and ADHD increase adaptive behavior deficits in all domains. However, these 2 factors interact to cause the greatest impairment in children with both prenatal alcohol exposure and ADHD for communication abilities. These results further demonstrate the deleterious effects of prenatal alcohol exposure and broaden our understanding of how ADHD exacerbates behavioral outcomes in this population. Copyright © 2014

  5. Effects of prenatal alcohol exposure on the developmental pattern of temperature preference in a thermocline.

    Science.gov (United States)

    Zimmerberg, B; Tomlinson, T M; Glaser, J; Beckstead, J W

    1993-01-01

    Prenatal alcohol exposure is associated with a variety of impairments in neonatal state regulatory systems. Since prenatal alcohol exposure causes thermoregulatory deficits in response to both heat and cold stress in rats, body temperature set-point might be altered in alcohol-exposed offspring. The effect of prenatal alcohol exposure on behavior in a thermocline was investigated in 10-, 15-, and 125-day-old male and female rats from three prenatal treatment conditions: alcohol liquid diet, pair-fed liquid diet control, or standard control. Subjects were placed in the thermocline in the cold, hot, or middle start positions and observed for 60 min. Subjects exposed to alcohol prenatally had a wider "preference zone" than control subjects at 10 and 15 days of age, but did not as adults. This widening of the temperature set-point in young subjects prenatally exposed to alcohol may represent a developmental lag in the development of body temperature set-point or a central compensatory process allowing the animal to adapt to alternating experiences of heat and cold stress.

  6. Epilogue: Understanding Children Who Have Been Affected by Maltreatment and Prenatal Alcohol Exposure--Future Directions

    Science.gov (United States)

    Hyter, Yvette D.; Way, Ineke

    2007-01-01

    This epilogue summarizes the six articles presented in the clinical forum focused on understanding children who have been affected by maltreatment and prenatal alcohol exposure. It presents common themes that emerged among the articles and future research directions.

  7. Comparison of motor delays in young children with fetal alcohol syndrome to those with prenatal alcohol exposure and with no prenatal alcohol exposure.

    Science.gov (United States)

    Kalberg, Wendy O; Provost, Beth; Tollison, Sean J; Tabachnick, Barbara G; Robinson, Luther K; Eugene Hoyme, H; Trujillo, Phyllis M; Buckley, David; Aragon, Alfredo S; May, Philip A

    2006-12-01

    Researchers are increasingly considering the importance of motor functioning of children with fetal alcohol spectrum disorder (FASD). The purpose of this study was to assess the motor development of young children with fetal alcohol syndrome (FAS) to determine the presence and degree of delay in their motor skills and to compare their motor development with that of matched children without FAS. The motor development of 14 children ages 20 to 68 months identified with FAS was assessed using the Vineland Adaptive Behavior Scales (VABS). In addition, 2 comparison groups were utilized. Eleven of the children with FAS were matched for chronological age, gender, ethnicity, and communication age to: (1) 11 children with prenatal alcohol exposure who did not have FAS and (2) 11 matched children without any reported prenatal alcohol exposure. The motor scores on the VABS were compared among the 3 groups. Most of the young children with FAS in this study showed clinically important delays in their motor development as measured on the VABS Motor Domain, and their fine motor skills were significantly more delayed than their gross motor skills. In the group comparisons, the young children with FAS had significantly lower Motor Domain standard (MotorSS) scores than the children not exposed to alcohol prenatally. They also had significantly lower Fine Motor Developmental Quotients than the children in both the other groups. No significant group differences were found in gross motor scores. For MotorSS scores and Fine Motor Developmental Quotients, the means and standard errors indicated a continuum in the scores from FAS to prenatal alcohol exposure to nonexposure. These findings strongly suggest that all young children with FAS should receive complete developmental evaluations that include assessment of their motor functioning, to identify problem areas and provide access to developmental intervention programs that target deficit areas such as fine motor skills. Fine motor

  8. Impaired Odor Identification in Children with Histories of Heavy Prenatal Alcohol Exposure

    Science.gov (United States)

    Bower, Emily; Szajer, Jacquelyn; Mattson, Sarah N.; Riley, Edward P.; Murphy, Claire

    2013-01-01

    Prenatal alcohol exposure can lead to behavioral and cognitive impairments across multiple domains. Many of the brain regions impacted by prenatal alcohol exposure are also linked with olfactory processing, and odor identification deficits have been documented in certain neurological disorders associated with these brain regions. As odor identification following prenatal alcohol exposure is not well studied, we compared odor identification in children with prenatal exposure to alcohol (AE) to typically developing controls (CON) (N = 16/group). It was hypothesized that children in the AE group would perform more poorly than children in the CON group on the San Diego Odor Identification Test, an identification test of 8 common household odorants. Children exposed to alcohol during prenatal development were significantly impaired in olfactory identification (M = 5.95, SE = 0.37) compared to typically developing controls (M = 7.24, SE = 0.37). These findings confirmed the hypothesis that prenatal exposure to alcohol is associated with odor identification deficits, and suggest that further research is warranted to identify the mechanisms underlying these deficits, the integrity of brain areas that are involved, and to determine whether olfactory performance might contribute to better identification of children at risk for behavioral and cognitive deficits. PMID:23683527

  9. Relationships between Head Circumference, Brain Volume and Cognition in Children with Prenatal Alcohol Exposure.

    Directory of Open Access Journals (Sweden)

    Sarah Treit

    Full Text Available Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144 and healthy controls (n = 145, aged 5-19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with

  10. Dissociation of "conscious desire" (craving) from and relapse in alcohol and cocaine dependence.

    Science.gov (United States)

    Miller, N S; Gold, M S

    1994-06-01

    Treatment of withdrawal and postabstinence craving has yielded mixed results in eliminating drug and alcohol use, improving outcomes, and reducing relapse in those patients addicted to alcohol and drugs. To assess the role of "conscious desire" (or craving) for drugs/alcohol during abstinence and withdrawal in continued addictive drug and alcohol use, we analyzed data from 1626 patients voluntarily admitted to a primary rehabilitation center in Minnesota. Eighty-one percent and 71% of all patients completed surveys at 6 and 12 months following discharge. Forty-two percent were diagnosed as alcohol dependent (AD) alone, 28% as alcohol and drug dependent (ADD) other than cocaine, and 25% as cocaine dependent (CD). At 6 months following discharge, the CD group had the lowest abstinence rate for drugs, at 83%, compared to the AD group, at 99%, and for alcohol, at 76%, compared to the AD group, at 75%. The AD group had the best outcomes and the least slippage from 6 to 12 months for drugs and alcohol. In all groups craving was not a major self-reported cause of relapse. For the CD subgroup, impulsive action with no known cause was the most common reason for relapse, while the AD group cited depression. These data agree with other reports in the literature suggesting that relapse is not commonly related to conscious craving. Our experience suggests that craving is rarely the first reason given for relapse. Drug seeking and use are such highly ritualized, automatic behaviors that the addict may appear not to require the intervention of conscious thoughts or distinct craving states to use.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. A decrease in the size of the basal ganglia following prenatal alcohol exposure: a preliminary report.

    Science.gov (United States)

    Mattson, S N; Riley, E P; Jernigan, T L; Garcia, A; Kaneko, W M; Ehlers, C L; Jones, K L

    1994-01-01

    Prenatal alcohol exposure is known to cause damage to the central nervous system. This study sought to further elucidate the structural brain damage that occurs following prenatal alcohol exposure in both children and rats. Two children with histories of maternal alcohol abuse but who did not qualify for a diagnosis of Fetal Alcohol Syndrome (FAS), based on established criteria, underwent magnetic resonance imaging. Reduced volumes were found for the cerebrum and cerebellum. In addition, the proportional volume of the basal ganglia was reduced, although the proportional volumes of cortical and subcortical fluid, cortical gray matter, limbic and nonlimbic cortex, and diencephalic structures were unaffected. These findings are compared with our recent MRI findings in two cases of FAS. In addition, the caudate-putamen and ventricular areas were assessed in rats exposed to alcohol prenatally. Whereas the overall brain section area was not reduced in size, the area of the caudate-putamen was reduced and that of the ventricles was enlarged.

  12. Prenatal alcohol exposure and traumatic childhood experiences: A systematic review.

    Science.gov (United States)

    Price, Alan; Cook, Penny A; Norgate, Sarah; Mukherjee, Raja

    2017-05-25

    Prenatal alcohol exposure (PAE) and traumatic childhood experiences (trauma) such as abuse or neglect can each cause central nervous system neurobiological changes or structural damage which can manifest as cognitive and behavioural dysfunction. In cases where both exposures have occurred, the risk of neurodevelopmental impairment may be greater, but this interaction has not been well studied. Here we present a systematic review that identified five primary research studies which investigated either the impact of trauma in children with PAE, or of PAE in children with trauma. Due to the heterogeneity of studies, narrative analysis was applied. Children in these cohorts with both exposures were more likely to show deficits in language, attention, memory and intelligence, and exhibit more severe behavioural problems than children with one exposure in absence of the other. However, the current literature is scarce and methodologically flawed. Further studies are required that: assess dual exposure in other neurodevelopmental domains; feature developmentally impaired yet non-exposed controls; and account for the wide spectrum of effects and different diagnostic criteria associated with PAE. Copyright © 2017. Published by Elsevier Ltd.

  13. [Perceived norms among Honduran university students about peers and tobacco, alcohol, marijuana and cocaine use].

    Science.gov (United States)

    Figueroa, Syntia Dinora Santos; Cunningham, John; Strike, Carol; Brands, Bruna; Wright, Maria da Gloria Miotto

    2009-01-01

    The purpose of this study was to assess the difference between perceived norms and peers' drug use among sophomore and junior university students (from the field of education) aged 18 to 24 years. The Social Norms Theory was used as the theoretical framework. In total, 286 students participated in the study, 67% of which reported having consumed alcohol at least once in a lifetime and 28% stated being daily users. Students perceived that 62% of their peers used tobacco and 63% used alcohol. The perceived norm for drug use was slightly higher in women than in men. In conclusion, there is an overestimation between the perceived norm and use of alcohol, tobacco, marijuana and cocaine.

  14. 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.

  15. Neurotoxicity of prenatal alcohol exposure on medullary pre-Bötzinger complex neurons in neonatal rats

    Institute of Scientific and Technical Information of China (English)

    Ming-li Ji; Yun-hong Wu; Zhi-bin Qian

    2015-01-01

    Prenatal alcohol exposure disrupts the development of normal fetal respiratory function, but whether it perturbs respiratory rhythmical discharge activity is unclear. Furthermore, it is un-known whether the 5-hydroxytryptamine 2A receptor (5-HT2AR) is involved in the effects of prenatal alcohol exposure. In the present study, pregnant female rats received drinking water containing alcohol at concentrations of 0%, 1%, 2%, 4%, 8% or 10% (v/v) throughout the gestation period. Slices of the medulla from 2-day-old neonatal rats were obtained to record respiratory rhythmical discharge activity. 5-HT2AR protein and mRNA levels in the pre-Bötzing-er complex of the respiratory center were measured by western blot analysis and quantitative RT-PCR, respectively. Compared with the 0% alcohol group, respiratory rhythmical discharge activity in medullary slices in the 4%, 8% and 10% alcohol groups was decreased, and the reduc-tion was greatest in the 8% alcohol group. Respiratory rhythmical discharge activity in the 10%alcohol group was irregular. Thus, 8% was the most effective alcohol concentration at attenuating respiratory rhythmical discharge activity. These ifndings suggest that prenatal alcohol exposure attenuates respiratory rhythmical discharge activity in neonatal rats by downregulating 5-HT2AR protein and mRNA levels.

  16. Prenatal alcohol exposure inducing the apoptosis of mossy cells in hippocampus of SMS2-/- mice.

    Science.gov (United States)

    Wang, Lai; Wu, Lin; Wang, Xiaoqing; Deng, Jiexin; Ma, Zhanyou; Fan, Wenjuan; He, Weiya; Deng, Jinbo

    2015-11-01

    In order to understand the mechanisms of alcohol-induced neuroapoptosis through the ceramide pathway, sphingomyelin synthase 2 knockout (SMS2-/-) mice were used to make the prenatal alcohol exposure model, and the role of ceramide regulation on alcohol-induced neuroapoptosis was studied in the offspring. Initially the levels of serum sphingomyelin (SM) were detected with enzymatic method in P0 pups after alcohol exposure in parents. Then the apoptosis of mossy cells in the offspring hippocampus was investigated after prenatal alcohol exposure with immunohistochemistry and TUNEL assay. Finally the expression of activated Caspase 8 and activated Caspase 3 in the offspring hippocampus was detected with Western blot analysis. Our results showed that SM levels were down-regulated in a dose-dependent manner (palcohol exposure in wild-type (WT) and SMS2-/- pups. However, SM levels of serum in SMS2-/- pups were significantly lower than that in WT pups (palcohol-induced neuroapoptosis. In both WT pups and SMS2-/- pups, the number of apoptotic mossy cells in the hippocampus increased after prenatal alcohol exposure in a dose dependent manner (palcohol exposure, consistent with results from TUNEL assay and immunocytochemistry. Our study suggests that mossy cells may be the easily attacked cells for fetal alcohol spectrum disorder (FASD), and ceramide is involved in the alcohol-induced neural apoptosis. The mechanism probably lies in the accumulated ceramide in SMS2 mice, and the increase of activated Caspase 8 and Caspase 3 promotes alcohol-induced neuroapoptosis.

  17. A Double Blind, Placebo-Controlled Trial that Combines Disulfiram and Naltrexone for Treating Co-Occurring Cocaine and Alcohol Dependence

    Science.gov (United States)

    Pettinati, Helen; Kampman, Kyle M.; Lynch, Kevin G.; Xie, Hu; Dackis, Charles; Rabinowitz, Amanda R.; O’Brien, Charles P.

    2008-01-01

    BACKGROUND This is a double blind, placebo-controlled trial that evaluated the efficacy of disulfiram, naltrexone and their combination in patients with co-occurring cocaine and alcohol dependence. METHODS 208 patients were randomized to disulfiram (250mg/day), naltrexone (100mg/day), the combination, or placebo for 11 weeks. Outcomes were in-trial abstinence from cocaine and/or alcohol. RESULTS Few safety concerns were reported, although medication adherence was low in a number of patients for both medications, alone or in combination. In the primary analyses (GEE modeling), abstinence from cocaine as measured by cocaine-negative urines and days of self-reported abstinence from cocaine or alcohol did not differ between placebo and any of the medication groups. However, patients taking disulfiram (alone or in combination) were most likely to achieve combined abstinence from cocaine and alcohol. Secondary analyses revealed that patients taking the disulfiram-naltrexone combination were most likely to achieve 3 consecutive weeks of abstinence from cocaine and alcohol. CONCLUSION There was an association between disulfiram treatment and abstinence from cocaine and alcohol. More patients taking the disulfiram-naltrexone combination achieved 3 consecutive weeks of abstinence in treatment than placebo-treated patients. PMID:18079068

  18. Executive control deficits in substance-dependent individuals: a comparison of alcohol, cocaine, and methamphetamine and of men and women

    NARCIS (Netherlands)

    E.A.A. van der Plas; E.A. Crone; W.P.M. van den Wildenberg; D. Tranel; A. Bechara

    2009-01-01

    Substance dependence is associated with executive function deficits, but the nature of these executive defects and the effect that different drugs and sex have on these defects have not been fully clarified. Therefore, we compared the performance of alcohol- (n = 33; 18 women), cocaine- (n = 27; 14

  19. Executive control deficits in substance-dependent individuals: a comparison of alcohol, cocaine, and methamphetamine and of men and women

    NARCIS (Netherlands)

    van der Plas, E.A.A.; Crone, E.A.; van den Wildenberg, W.P.M.; Tranel, D.; Bechara, A.

    2009-01-01

    Substance dependence is associated with executive function deficits, but the nature of these executive defects and the effect that different drugs and sex have on these defects have not been fully clarified. Therefore, we compared the performance of alcohol- (n = 33; 18 women), cocaine- (n = 27; 14

  20. A systematic review of the effectiveness of the community reinforcement approach in alcohol, cocaine and opioid addiction

    NARCIS (Netherlands)

    Roozen, H.G.; Boulogne, J.J.; Tulder, M.W. van; Brink, W. van den; Jong, C.A.J. de; Kerkhof, A.J.F.M.

    2004-01-01

    The community reinforcement approach (CRA) has been applied in the treatment of disorders resulting from alcohol, cocaine and opioid use. The objectives were to review the effectiveness of (1) CRA compared with usual care, and (2) CRA versus CRA plus contingency management. Studies were selected thr

  1. A systematic review of the effectiveness of the community reinforcement approach in alcohol, cocaine and opioid addiction.

    NARCIS (Netherlands)

    Roozen, H.G.; Boulogne, J.J.; Tulder, van M.; Brink, van den W.; Jong, de C.A.J.; Kerkhof, A.J.F.M.

    2004-01-01

    Abstract The community reinforcement approach (CRA) has been applied in the treatment of disorders resulting from alcohol, cocaine and opioid use. The objectives were to review the effectiveness of (1) CRA compared with usual care, and (2) CRA versus CRA plus contingency management. Studies were sel

  2. Prenatal alcohol exposure alters expression of neurogenesis-related genes in an ex vivo cell culture model

    OpenAIRE

    Tyler, Christina R; Allan, Andrea M.

    2014-01-01

    Prenatal alcohol exposure can lead to long-lasting changes in functional and genetic programs of the brain, which may underlie behavioral alterations seen in Fetal Alcohol Spectrum Disorder (FASD). Aberrant fetal programming during gestational alcohol exposure is a possible mechanism by which alcohol imparts teratogenic effects on the brain; however, current methods used to investigate the effects of alcohol on development often rely on either direct application of alcohol in vitro or acute h...

  3. [Effects of prenatal alcohol consumption upon fecundity, natality, growth, vaginal opening and sexual cycle in the rat (author's transl)].

    Science.gov (United States)

    Fueyo-Silva, A; Menéndez-Patterson, A; Marin, B

    1980-01-01

    The purpose of this study was to investigate the action of prenatal alcohol consumption upon offspring and sexual maturity parameters on a rat strain which, for several years, drank only a brandy/water solution. With regard to fecundity and number of pups our results show no variation, while weight, vaginal opening, and sexual cycle are severely affected by alcohol intake. Possible alterations upon offspring due to chronic prenatal alcohol intake are examined.

  4. Automated cerebellar segmentation: Validation and application to detect smaller volumes in children prenatally exposed to alcohol

    Directory of Open Access Journals (Sweden)

    Valerie A. Cardenas

    2014-01-01

    Discussion: These results demonstrate excellent reliability and validity of automated cerebellar volume and mid-sagittal area measurements, compared to manual measurements. These data also illustrate that this new technology for automatically delineating the cerebellum leads to conclusions regarding the effects of prenatal alcohol exposure on the cerebellum consistent with prior studies that used labor intensive manual delineation, even with a very small sample.

  5. Prologue: Understanding Children Who Have Been Affected by Maltreatment and Prenatal Alcohol Exposure

    Science.gov (United States)

    Hyter, Yvette D.

    2007-01-01

    This prologue introduces an important topic for multiple disciplines involved with children and their families. This introduction includes a review of some of the current literature on the effects of maltreatment and prenatal alcohol exposure on child development, an explanation of why this topic is essential learning for communication…

  6. Prenatal Alcohol Exposure and the Developing Immune System.

    Science.gov (United States)

    Gauthier, Theresa W

    2015-01-01

    Evidence from research in humans and animals suggest that ingesting alcohol during pregnancy can disrupt the fetal immune system and result in an increased risk of infections and disease in newborns that may persist throughout life. Alcohol may have indirect effects on the immune system by increasing the risk of premature birth, which itself is a risk factor for immune-related problems. Animal studies suggest that alcohol exposure directly disrupts the developing immune system. A comprehensive knowledge of the mechanisms underlying alcohol's effects on the developing immune system only will become clear once researchers establish improved methods for identifying newborns exposed to alcohol in utero.

  7. Is serum brain-derived neurotrophic factor related to craving for or use of alcohol, cocaine, or methamphetamine?

    Directory of Open Access Journals (Sweden)

    Gangwani P

    2011-06-01

    Full Text Available Craig Hilburn, Vicki A Nejtek, Wendy A Underwood, Meharvan Singh, Gauravkumar Patel, Pooja Gangwani, Michael J ForsterUniversity of North Texas Health Science Center at Fort Worth, TX, USABackground: Data suggests that brain-derived neurotropic factor (BDNF plays a neuroadaptive role in addiction. Whether serum BDNF levels are different in alcohol or psychostimulants as a function of craving is unknown. Here, we examined craving and serum BDNF levels in persons with alcohol versus psychostimulant dependence. Our goals were to explore BDNF as an objective biomarker for 1 craving 2 abstinence, and 3 years of chronic substance use.Methods: An exploratory, cross-sectional study was designed. Men and women between 20–65 years old with alcohol, cocaine, or methamphetamine dependence were eligible. A craving questionnaire was used to measure alcohol, cocaine and methamphetamine cravings. Serum levels of BDNF were measured using enzyme linked immunoassay. Analysis of variance, chi-square, and correlations were performed using a 95% confidence interval and a significance level of P < 0.05.Results: We found a significant difference in the mean craving score among alcohol, cocaine and methamphetamine dependent subjects. There were no significant influences of race, gender, psychiatric disorder or psychotropic medication on serum BDNF levels. We found that among psychostimulant users BDNF levels were significantly higher in men than in women when the number of abstinent days was statistically controlled. Further, a significant correlation between serum BDNF levels and the number of abstinent days since last psychostimulant use was found.Conclusion: These data suggest that BDNF may be a biomarker of abstinence in psychostimulant dependent subjects and inform clinicians about treatment initiatives. The results are interpreted with caution due to small sample size and lack of a control group.Keywords: BDNF, alcohol, cocaine, methamphetamine, craving

  8. The effects of prenatal and postnatal (via nursing) exposure to alcohol in rats

    Energy Technology Data Exchange (ETDEWEB)

    Nekvasil, N.; Baggio, C. (St. Mary' s Coll., Notre Dame, IN (United States))

    1992-02-26

    Pregnant and post-partum rats were given daily doses of 20% alcohol during days 13-21 gestation and postnatal days 3-12, respectively. Following exposure, all rat pups, were tested for balance, blood pressure, right and left cerebral hemisphere weights, and cerebellar weight. Results were grouped according to exposure and gender. The postnatal group was the only one to demonstrate difficulties with balance. The mean arterial pressure in males exposed postnatally was significantly lower than the control and prenatal males. Females exposed postnatally had a significantly higher blood pressure than control females. Within the postnatal group, males had a significantly lower blood pressure than the females. Prenatal and control females differed significantly for left cerebral hemisphere (LCH) weight with the prenatal weighing less. Male pups exposed prenatally had significantly heavier LCH than the postnatal and control males. For both males and females, postnatal LCH weights did not differ from those of the control pups. Within the prenatal group, the LCH weight in females was significantly lower than in males. Mean cerebellar weights were significantly lower in postnatal animals compared to control animals. A major finding of this study is that the effect of alcohol exposure on rat pups depends on gender and developmental age.

  9. Prenatal exposure to cigarettes, alcohol, and coffee and the risk for febrile seizures

    DEFF Research Database (Denmark)

    Vestergaard, M; Wisborg, K; Henriksen, TB

    2005-01-01

    of extensive brain growth and differentiation in this period. We evaluated the association between prenatal exposure to cigarettes, alcohol, and coffee and the risk for febrile seizures in 2 population-based birth cohorts. METHODS: The Aarhus Birth Cohort consisted of 25,196 children of mothers who were...... Birth Cohort, but the corresponding association was weak in the Aalborg-Odense cohort. We found no association between maternal alcohol and coffee consumption and the risk for febrile seizures. The results were similar for simple and complex febrile seizures. CONCLUSIONS: Our data suggest that prenatal...... exposure to low to moderate levels of alcohol and coffee has no impact on the risk for febrile seizures, whereas a modest smoking effect cannot be ruled out....

  10. Cognitive factors contributing to spelling performance in children with prenatal alcohol exposure.

    Science.gov (United States)

    Glass, Leila; Graham, Diana M; Akshoomoff, Natacha; Mattson, Sarah N

    2015-11-01

    Heavy prenatal alcohol exposure is associated with impaired school functioning. Spelling performance has not been comprehensively evaluated. We examined whether children with heavy prenatal alcohol exposure demonstrate deficits in spelling and related abilities, including reading, and tested whether there are unique underlying mechanisms for observed deficits in this population. Ninety-six school-age children made up 2 groups: children with heavy prenatal alcohol exposure (AE, n = 49) and control children (CON, n = 47). Children completed select subtests from the Wechsler Individual Achievement Test-Second Edition and the NEPSY-II. Group differences and relations between spelling and theoretically related cognitive variables were evaluated using multivariate analysis of variance and Pearson correlations. Hierarchical regression analyses were used to assess contributions of group membership and cognitive variables to spelling performance. The specificity of these deficits and underlying mechanisms was tested by examining the relations between reading ability, group membership, and cognitive variables. Groups differed significantly on all variables. Group membership and phonological processing significantly contributed to spelling performance, whereas for reading, group membership and all cognitive variables contributed significantly. For both reading and spelling, group × working memory interactions revealed that working memory contributed independently only for alcohol-exposed children. Alcohol-exposed children demonstrated a unique pattern of spelling deficits. The relation of working memory to spelling and reading was specific to the AE group, suggesting that if prenatal alcohol exposure is known or suspected, working memory ability should be considered in the development and implementation of explicit instruction. (c) 2015 APA, all rights reserved).

  11. Moderate Level Alcohol During Pregnancy, Prenatal Stress, or Both and Limbic-Hypothalamic-Pituitary-Adrenocortical Axis Response to Stress in Rhesus Monkeys

    Science.gov (United States)

    Schneider, Mary L.; Moore, Colleen F.; Kraemer, Gary W.

    2004-01-01

    This study examined the relationship between moderate-level prenatal alcohol exposure, prenatal stress, and postnatal response to a challenging event in 6-month-old rhesus monkeys. Forty-one rhesus monkey (Macaca mulatta) infants were exposed prenatally to moderate level alcohol, maternal stress, or both. Offspring plasma cortisol and…

  12. Moderate Level Alcohol During Pregnancy, Prenatal Stress, or Both and Limbic-Hypothalamic-Pituitary-Adrenocortical Axis Response to Stress in Rhesus Monkeys

    Science.gov (United States)

    Schneider, Mary L.; Moore, Colleen F.; Kraemer, Gary W.

    2004-01-01

    This study examined the relationship between moderate-level prenatal alcohol exposure, prenatal stress, and postnatal response to a challenging event in 6-month-old rhesus monkeys. Forty-one rhesus monkey (Macaca mulatta) infants were exposed prenatally to moderate level alcohol, maternal stress, or both. Offspring plasma cortisol and…

  13. GABAergic gene expression in postmortem hippocampus from alcoholics and cocaine addicts; corresponding findings in alcohol-naive P and NP rats.

    Directory of Open Access Journals (Sweden)

    Mary-Anne Enoch

    Full Text Available BACKGROUND: By performing identical studies in humans and rats, we attempted to distinguish vulnerability factors for addiction from neurobiological effects of chronic drug exposure. We focused on the GABAergic system within the hippocampus, a brain region that is a constituent of the memory/conditioning neuronal circuitry of addiction that is considered to be important in drug reinforcement behaviors in animals and craving and relapse in humans. METHODOLOGY: Using RNA-Seq we quantified mRNA transcripts in postmortem total hippocampus from alcoholics, cocaine addicts and controls and also from alcohol-naïve, alcohol preferring (P and non-preferring (NP rats selectively bred for extremes of alcohol-seeking behavior that also show a general addictive tendency. A pathway-targeted analysis of 25 GABAergic genes encoding proteins implicated in GABA synthesis, metabolism, synaptic transmission and re-uptake was undertaken. PRINCIPAL FINDINGS: Directionally consistent and biologically plausible overlapping and specific changes were detected: 14/25 of the human genes and 12/25 of the rat genes showed nominally significant differences in gene expression (global p values: 9×10⁻¹⁴, 7×10⁻¹¹ respectively. Principal FDR-corrected findings were that GABBR1 was down-regulated in alcoholics, cocaine addicts and P rats with congruent findings in NSF, implicated in GABAB signaling efficacy, potentially resulting in increased synaptic GABA. GABRG2, encoding the gamma2 subunit required for postsynaptic clustering of GABAA receptors together with GPHN, encoding the associated scaffolding protein gephryin, were both down-regulated in alcoholics and cocaine addicts but were both up-regulated in P rats. There were also expression changes specific to cocaine addicts (GAD1, GAD2, alcoholics (GABRA2 and P rats (ABAT, GABRG3. CONCLUSIONS/SIGNIFICANCE: Our study confirms the involvement of the GABAergic system in alcoholism but also reveals a hippocampal GABA

  14. Parenting under the influence: the effects of opioids, alcohol and cocaine on mother-child interaction.

    Science.gov (United States)

    Slesnick, Natasha; Feng, Xin; Brakenhoff, Brittany; Brigham, Gregory S

    2014-05-01

    Nearly 20% of adults receiving treatment for a substance use disorder live with their minor children (Stanger et al., 1999) and women in drug use treatment are twice as likely as men to have children in their household (Wechsberg et al., 1998). Parental drug use impacts the family through reduced family resources such as money and food, and researchers consistently note parenting deficits among substance users (Solis, Shadur, Burns, & Hussong, 2012). Little is known about differences in parenting and mother-child interaction among mothers with different drugs of choice or among mothers of older children, between 8 and 16 years. This study reports the findings from a sample of treatment seeking opioid, alcohol and cocaine using mothers and their 8-16-year-old child. Findings from a mother-child observational task and self-reported parenting measure indicated less undermining autonomy and higher mother maternal acceptance among opioid compared to alcohol addicted mothers. African American mothers were observed to have fewer negative interactional behaviors than Whites and both African American mothers and children self-reported higher firm control and maternal acceptance. Overall, mothers appeared to struggle with effective discipline with older versus younger children. Findings offer useful information to clinicians seeking to effectively tailor their interventions to women and children who present with different drugs of abuse, race/culture and developmental stage of child. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Effects of prenatal alcohol exposure on social behavior in humans and other species.

    Science.gov (United States)

    Kelly, S J; Day, N; Streissguth, A P

    2000-01-01

    Alcohol exposure during development causes central nervous system alterations in both humans and animals. Although the most common behavioral manifestation of these alterations is a reduction in cognitive abilities, it is becoming increasingly apparent that deficits in social behavior may be very prevalent sequelae of developmental alcohol exposure. In infancy and early childhood, deficits in attachment behavior and state regulation are seen in both alcohol-exposed people and animals, suggesting that these changes are largely the result of the alcohol exposure rather than maternal behavior. In the periadolescent period, people exposed to alcohol during development show a variety of difficulties in the social domain as measured by checklists filled out by either a parent or teacher. Rats exposed to alcohol during development show changes in play and parenting behaviors. In adulthood, prenatal alcohol exposure is related to high rates of trouble with the law, inappropriate sexual behavior, depression, suicide, and failure to care for children. These high rates all suggest that there may be fundamental problems in the social domain. In other animals, perinatal alcohol exposure alters aggression, active social interactions, social communication and recognition, maternal behavior, and sexual behavior in adults. In conclusion, research suggests that people exposed to alcohol during development may exhibit striking changes in social behavior; the animal research suggests that these changes may be largely the result of the alcohol insult and not the environment.

  16. Cost-effectiveness of peer-delivered interventions for cocaine and alcohol abuse among women: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Jennifer Prah Ruger

    Full Text Available AIMS: To determine whether the additional interventions to standard care are cost-effective in addressing cocaine and alcohol abuse at 4 months (4 M and 12 months (12 M from baseline. METHOD: We conducted a cost-effectiveness analysis of a randomized controlled trial with three arms: (1 NIDA's Standard intervention (SI; (2 SI plus a Well Woman Exam (WWE; and, (3 SI, WWE, plus four Educational Sessions (4ES. RESULTS: To obtain an additional cocaine abstainer, WWE compared to SI cost $7,223 at 4 M and $3,611 at 12 M. Per additional alcohol abstainer, WWE compared to SI cost $3,611 and $7,223 at 4 M and 12 M, respectively. At 12 M, 4ES was dominated (more costly and less effective by WWE for abstinence outcomes. CONCLUSIONS: To our knowledge, this is the first cost-effectiveness analysis simultaneously examining cocaine and alcohol abuse in women. Depending on primary outcomes sought and priorities of policy makers, peer-delivered interventions can be a cost-effective way to address the needs of this growing, underserved population. TRIAL REGISTRATION: ClinicalTrials.gov NCT01235091.

  17. NEUROPSYCHOLOGICAL DEFICITS ASSOCIATED WITH HEAVY PRENATAL ALCOHOL EXPOSURE ARE NOT EXACERBATED BY COMORBID ADHD

    Science.gov (United States)

    Glass, Leila; Ware, Ashley L.; Crocker, Nicole; Deweese, Benjamin N.; Coles, Claire D.; Kable, Julie A.; May, Philip A.; Kalberg, Wendy O.; Sowell, Elizabeth R.; Jones, Kenneth Lyons; Riley, Edward P.; Mattson, Sarah N.

    2013-01-01

    Objective: Neuropsychological functioning of individuals with attention-deficit/hyperactivity disorder (ADHD) or heavy prenatal alcohol exposure has been well documented independently. This study examined the interaction between both factors on cognitive performance in children. Method: As part of a multisite study, 344 children (8-16y, M=12.28, SD=2.52) completed a comprehensive neuropsychological battery. Four subject groups were tested: children with histories of heavy prenatal alcohol exposure (AE) and ADHD (AE+, n=90), alcohol-exposed without ADHD, (AE−, n=38), non-exposed with ADHD (ADHD, n=80), and non-exposed without ADHD (CON, n=136). Results: Separate 2(AE) × 2(ADHD) MANCOVAs revealed significant main and interactive effects of ADHD and AE on overall WISC-IV, D-KEFS, and CANTAB performance. Individual ANOVAs revealed significant interactions on 2 WISC-IV indices [Verbal Comprehension (VCI), Perceptual Reasoning (PRI)], and four D-KEFS and CANTAB subtests [Design Fluency, Verbal Fluency, Trail Making, Spatial Working Memory]. Follow-up analyses demonstrated no difference between AE+ and AE− groups on any measures. The combined AE+/− group demonstrated more severe impairment than the ADHD group on VCI and PRI, but there were no other differences between clinical groups. Conclusions: These results support a combined AE+/− group for neuropsychological research and indicate that, in some cases, the neuropsychological effects seen in ADHD are altered by prenatal alcohol exposure. The effects of alcohol exposure on verbal comprehension and perceptual reasoning were greater than those related to having ADHD without alcohol exposure, although both conditions independently resulted in cognitive impairment compared to controls. Clinically, these findings demonstrate task-dependent patterns of impairment across clinical disorders. PMID:24040921

  18. Understanding Specific Effects of Prenatal Alcohol Exposure on Brain Structure in Young Adults

    OpenAIRE

    Chen, Xiangchuan; Coles, Claire D.; Lynch, Mary E; Hu, Xiaoping

    2011-01-01

    Prenatal alcohol exposure (PAE) is associated with various adverse effects on human brain and behavior. Recently, neuroimaging studies have begun to identify PAE effects on specific brain structures. Investigation of such specific PAE effects is important for understanding the teratogenic mechanism of PAE on human brain, which is critical for differentiating PAE from other disorders. In this structural MRI study with young adults, PAE effects on the volumes of automatically segmented cortical...

  19. Unintentional drug overdose death trends in New Mexico, USA, 1990-2005: combinations of heroin, cocaine, prescription opioids and alcohol.

    Science.gov (United States)

    Shah, Nina G; Lathrop, Sarah L; Reichard, R Ross; Landen, Michael G

    2008-01-01

    To determine the contribution of heroin, prescription opioids, cocaine and alcohol/drug combinations to the total overdose death rate and identify changes in drug overdose patterns among New Mexico subpopulations. We analyzed medical examiner data for all unintentional drug overdose deaths in New Mexico during 1990-2005. Age-adjusted drug overdose death rates were calculated by sex and race/ethnicity; we modeled overall drug overdose death adjusting for age and region. The total unintentional drug overdose death rate in New Mexico increased from 5.6 per 100 000 in 1990 to 15.5 per 100 000 in 2005. Deaths caused by heroin, prescription opioids, cocaine and alcohol/drug combinations together ranged from 89% to 98% of the total. Heroin caused the most deaths during 1990-2005, with a notable rate increase in prescription opioid overdose death during 1998-2005 (58%). During 1990-2005, the 196% increase in single drug category overdose death was driven by prescription opioids alone and heroin alone; the 148% increase in multi-drug category overdose death was driven by heroin/alcohol and heroin/cocaine. Hispanic males had the highest overdose death rate, followed by white males, white females, Hispanic females and American Indians. The most common categories causing death were heroin alone and heroin/alcohol among Hispanic males, heroin/alcohol among American Indian males and prescription opioids alone among white males and all female subpopulations. Interventions to prevent drug overdose death should be targeted according to use patterns among at-risk subpopulations. A comprehensive approach addressing both illicit and prescription drug users, and people who use these drugs concurrently, is needed to reduce overdose death.

  20. The effects of price and perceived quality on the behavioural economics of alcohol, amphetamine, cannabis, cocaine, and ecstasy purchases.

    Science.gov (United States)

    Goudie, Andrew J; Sumnall, Harry R; Field, Matt; Clayton, Hannah; Cole, Jon C

    2007-07-10

    Behavioural economic models of substance use describe the relationship between changes in unit price and consumption. However, these models rarely take account of the perceived quality (i.e. potency) of controlled drugs. Therefore we investigated the effects of both price and quality on the decision to purchase controlled drugs by polysubstance misusers. Forty current polysubstance misusers (29 males, 11 females; mean age 23.8) were recruited into the study. Participants were asked to hypothetically purchase drugs from a price list of alcohol, amphetamine, cannabis, cocaine and ecstasy at different levels of quality and price (i.e. better quality drugs cost more money). The disposable income available for those purchases was systematically varied in order to determine the impact of income on the decision to purchase drugs. Demand for both normal and strong alcohol was income inelastic. Demand for both poor and average quality cannabis and ecstasy was income inelastic, but demand for good quality cannabis and ecstasy was income elastic. The demand for poor quality cocaine was income inelastic, with the demand for both average and good quality cocaine being income elastic. Participants reported too few purchases of amphetamine, which precluded behavioural economic analysis. These results suggest that, like other goods, controlled drugs are purchased based upon the consumer's interpretations of their relative value. Therefore, it is probable that the purchase and subsequent use of controlled drugs by polysubstance misusers will be heavily influenced by the economic environment.

  1. Main mental disorders in crack-cocaine users treated at Psychosocial Care Centers for Alcohol and Drugs in the city of Recife, Brazil

    Directory of Open Access Journals (Sweden)

    Antonio Gomes de Castro Neto

    Full Text Available Abstract Introduction: Brazil's Northeast region has the highest crack-cocaine consumption in the country. Crack-cocaine has more intense effects than cocaine powder and can cause greater chemical dependence. Psychosocial Care Centers for Alcohol and Drugs (CAPSad are public health services that provide treatment for drug dependence. It is common for drug users, and particularly crack-cocaine users, to develop mental disorders. Objective: To evaluate the most common mental disorders in crack-cocaine dependents in treatment at CAPSad in the city of Recife, Brazil. Methods: The research database "Between rocks and shots: user profiles, consumption strategies, and social impact of crack cocaine" (CEP/CCS/UFPE no. 206/11 was consulted to establish the areas of crack cocaine consumption in the city of Recife. Results: There were 885 patients in treatment for crack-cocaine use, with a mean age of 29.8±9.4 years. The mean duration of drug use was 6.1±4.6 years. Most of the patients were males (80.3%, had left school at some point between the 1st and 9th grades (45.6%, were unemployed and/or seeking employment (52% and used drugs daily (56.4%. Cocaine chemical dependence was more significant when correlated with use of crack-cocaine and other drugs such as medications and hallucinogens (p = 0.01. Conclusions: Data from this study showed strong associations between crack-cocaine uses and development of mental disorders, particularly when abuse of multiple substances occurs. Based on these data, there is a clear need for coordination of related public policies for support and social reintegration to provide these people with comprehensive care.

  2. RE-AIM evaluation of the Alcohol and Pregnancy Project: educational resources to inform health professionals about prenatal alcohol exposure and fetal alcohol spectrum disorder.

    Science.gov (United States)

    Payne, Janet M; France, Kathryn E; Henley, Nadine; D'Antoine, Heather A; Bartu, Anne E; O'Leary, Colleen M; Elliott, Elizabeth J; Bower, Carol; Geelhoed, Elizabeth

    2011-03-01

    The objective was to evaluate the Alcohol and Pregnancy Project that provided health professionals in Western Australia (WA) with educational resources to inform them about prevention of prenatal alcohol exposure and fetal alcohol spectrum disorder (FASD). The authors developed, produced, and distributed educational resources to 3,348 health professionals in WA. Six months later, they surveyed 1,483 of these health professionals. The authors used the RE-AIM framework (reach, effectiveness, adoption, implementation, and maintenance) to evaluate the project. The educational resources were effective in producing a 31% increase in the proportion of health professionals who routinely provided pregnant women with information about the consequences of drinking alcohol during pregnancy. One hundred percent of the settings adopted the project, it reached 96.3% of the target population, it was implemented as intended, and the resources were maintained (http://www.ichr.uwa.edu.au/alcoholandpregnancy). The educational resources for health professionals have potential to contribute to reducing prenatal alcohol exposure and FASD.

  3. Prenatal exposure to cigarettes, alcohol, and coffee and the risk for febrile seizures

    DEFF Research Database (Denmark)

    Vestergaard, M; Wisborg, K; Henriksen, TB

    2005-01-01

    OBJECTIVE: Febrile seizure is a common type of seizure in childhood, probably caused by both genetic and early environmental factors. Little is known about the effect of environmental factors that operate in prenatal life, although the fetal brain may be particular vulnerable as a result...... of extensive brain growth and differentiation in this period. We evaluated the association between prenatal exposure to cigarettes, alcohol, and coffee and the risk for febrile seizures in 2 population-based birth cohorts. METHODS: The Aarhus Birth Cohort consisted of 25,196 children of mothers who were...... follow-up. We extracted from medical records additional information on febrile seizures in children in the Aarhus Birth Cohort who were born between 1989 and 1992. RESULTS: We found a slightly increased risk for febrile seizures in children who were exposed to 10 or more cigarettes per day in the Aarhus...

  4. Ethylglucuronide in Maternal Hair as a Biomarker of Prenatal Alcohol Exposure

    OpenAIRE

    Gutierrez, Hilda L.; Hund, Lauren; Shrestha, Shikhar; Rayburn, William F.; Leeman, Lawrence; Savage, Daniel D.; Bakhireva, Ludmila N.

    2015-01-01

    While direct ethanol metabolites, including ethylglucuronide (EtG), play an important role for the confirmation of prenatal alcohol exposure (PAE), their utility is often limited by their short half-lives in blood and urine. Maternal hair might allow for a retrospective measure of PAE for up to several months. This study examined the validity of hair EtG (hEtG) relative to self-reporting and five other biomarkers (gamma glutamyltranspeptidase [GGT], carbohydrate-deficient transferrin [%dCDT],...

  5. Prenatal exposure to cigarettes, alcohol, and coffee and the risk for febrile seizures

    DEFF Research Database (Denmark)

    Vestergaard, M; Wisborg, K; Henriksen, TB

    2005-01-01

    of extensive brain growth and differentiation in this period. We evaluated the association between prenatal exposure to cigarettes, alcohol, and coffee and the risk for febrile seizures in 2 population-based birth cohorts. METHODS: The Aarhus Birth Cohort consisted of 25,196 children of mothers who were...... follow-up. We extracted from medical records additional information on febrile seizures in children in the Aarhus Birth Cohort who were born between 1989 and 1992. RESULTS: We found a slightly increased risk for febrile seizures in children who were exposed to 10 or more cigarettes per day in the Aarhus...

  6. A tensor-based morphometry analysis of regional differences in brain volume in relation to prenatal alcohol exposure

    Directory of Open Access Journals (Sweden)

    E.M. Meintjes

    2014-01-01

    Full Text Available Reductions in brain volumes represent a neurobiological signature of fetal alcohol spectrum disorders (FASD. Less clear is how regional brain tissue reductions differ after normalizing for brain size differences linked with FASD and whether these profiles can predict the degree of prenatal exposure to alcohol. To examine associations of regional brain tissue excesses/deficits with degree of prenatal alcohol exposure and diagnosis with and without correction for overall brain volume, tensor-based morphometry (TBM methods were applied to structural imaging data from a well-characterized, demographically homogeneous sample of children diagnosed with FASD (n = 39, 9.6–11.0 years and controls (n = 16, 9.5–11.0 years. Degree of prenatal alcohol exposure was significantly associated with regionally pervasive brain tissue reductions in: (1 the thalamus, midbrain, and ventromedial frontal lobe, (2 the superior cerebellum and inferior occipital lobe, (3 the dorsolateral frontal cortex, and (4 the precuneus and superior parietal lobule. When overall brain size was factored out of the analysis on a subject-by-subject basis, no regions showed significant associations with alcohol exposure. FASD diagnosis was associated with a similar deformation pattern, but few of the regions survived FDR correction. In data-driven independent component analyses (ICA regional brain tissue deformations successfully distinguished individuals based on extent of prenatal alcohol exposure and to a lesser degree, diagnosis. The greater sensitivity of the continuous measure of alcohol exposure compared with the categorical diagnosis across diverse brain regions underscores the dose dependence of these effects. The ICA results illustrate that profiles of brain tissue alterations may be a useful indicator of prenatal alcohol exposure when reliable historical data are not available and facial features are not apparent.

  7. Prenatal Alcohol Exposure in Rodents As a Promising Model for the Study of ADHD Molecular Basis

    Science.gov (United States)

    Rojas-Mayorquín, Argelia E.; Padilla-Velarde, Edgar; Ortuño-Sahagún, Daniel

    2016-01-01

    A physiological parallelism, or even a causal effect relationship, can be deducted from the analysis of the main characteristics of the “Alcohol Related Neurodevelopmental Disorders” (ARND), derived from prenatal alcohol exposure (PAE), and the behavioral performance in the Attention-deficit/hyperactivity disorder (ADHD). These two clinically distinct disease entities, exhibits many common features. They affect neurological shared pathways, and also related neurotransmitter systems. We briefly review here these parallelisms, with their common and uncommon characteristics, and with an emphasis in the subjacent molecular mechanisms of the behavioral manifestations, that lead us to propose that PAE in rats can be considered as a suitable model for the study of ADHD. PMID:28018163

  8. Neuronal reduction in frontal cortex of primates after prenatal alcohol exposure.

    Science.gov (United States)

    Burke, Mark W; Palmour, Roberta M; Ervin, Frank R; Ptito, Maurice

    2009-01-07

    Children with fetal alcohol spectrum disorders (FASD) show behavioral and intellectual impairments that indicate frontal lobe dysfunction, but the extent of damage to this region has not been clarified by brain imaging studies. This study uses the St Kitts vervet monkey, a species that voluntarily consumes beverage alcohol, to examine the effects of prenatal ethanol exposure. Pregnant vervets were allowed to drink the equivalent of 3-5 standard drinks four times a week during the third trimester. Using unbiased stereology, we estimated neuronal reduction and found significantly fewer cells in the frontal lobes of FASD offspring as well as an increased density of interstitial white matter neurons. These cytoarchitectonic effects are consistent with the behavioral and cognitive changes observed in FASD.

  9. Visual-spatial abilities relate to mathematics achievement in children with heavy prenatal alcohol exposure.

    Science.gov (United States)

    Crocker, Nicole; Riley, Edward P; Mattson, Sarah N

    2015-01-01

    The current study examined the relationship between mathematics and attention, working memory, and visual memory in children with heavy prenatal alcohol exposure and controls. Subjects were 56 children (29 AE, 27 CON) who were administered measures of global mathematics achievement (WRAT-3 Arithmetic & WISC-III Written Arithmetic), attention, (WISC-III Digit Span forward and Spatial Span forward), working memory (WISC-III Digit Span backward and Spatial Span backward), and visual memory (CANTAB Spatial Recognition Memory and Pattern Recognition Memory). The contribution of cognitive domains to mathematics achievement was analyzed using linear regression techniques. Attention, working memory, and visual memory data were entered together on Step 1 followed by group on Step 2, and the interaction terms on Step 3. Model 1 accounted for a significant amount of variance in both mathematics achievement measures; however, model fit improved with the addition of group on Step 2. Significant predictors of mathematics achievement were Spatial Span forward and backward and Spatial Recognition Memory. These findings suggest that deficits in spatial processing may be related to math impairments seen in FASD. In addition, prenatal alcohol exposure was associated with deficits in mathematics achievement, above and beyond the contribution of general cognitive abilities. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  10. 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.

  11. Comparison of Adaptive Behavior in Children With Heavy Prenatal Alcohol Exposure or Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Crocker, Nicole; Vaurio, Linnea; Riley, Edward P.; Mattson, Sarah N.

    2012-01-01

    Background Adaptive behavior, the ability to respond successfully to everyday demands, may be especially sensitive to the effects of heavy prenatal alcohol exposure. Similar adaptive dysfunction is common in other developmental disorders including attention-deficit/hyperactivity disorder (ADHD). ADHD is frequently present in alcohol-exposed children and this overlap in clinical presentation makes identification of alcohol-exposed children difficult. Direct comparison of children with prenatal alcohol exposure and ADHD may yield distinct patterns of cognitive and behavioral performance and add to growing knowledge of the neuropsychological and behavioral profile of prenatal alcohol exposure. Therefore, the aim of the current study was to compare adaptive behavior in children with histories of heavy prenatal alcohol exposure (ALC), nonexposed children with ADHD (ADHD), and typically developing controls (CON). Methods Sixty-five children (ALC = 22, ADHD = 23, CON = 20) were selected from a larger ongoing study of the behavioral teratogenicity of alcohol. Alcohol-exposed and control participants were selected to match the ADHD subjects on age, sex, socioeconomic status, and race/ethnicity. Caregivers were administered the Vineland Adaptive Behavior Scales, a semi-structured interview, and were asked to rate their child’s behavior on 3 domains of adaptive function. Data were analyzed using regression techniques. Results Relative to controls, children in both the ALC and ADHD groups showed adaptive behavior deficits on all 3 domains and children in the ALC group were significantly more impaired than the ADHD group on the daily living skills domain. Within the ALC group, socialization standard scores were lower at older ages. This negative relationship between age and standard scores in the ALC group was also observed on the communication domain, a finding not previously reported. Conclusions This study suggests that both children with prenatal alcohol exposure and

  12. Prenatal exposure to alcohol and 3,4-methylenedioxymethamphetamine (ecstasy) alters adult hippocampal neurogenesis and causes enduring memory deficits.

    Science.gov (United States)

    Canales, Juan J; Ferrer-Donato, Agueda

    2014-01-01

    Recreational drug use among pregnant women is a source of concern due to potential harmful effects of drug exposure on prenatal and infant development. The simultaneous abuse of ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] and alcohol is prevalent among young adults, including young expectant mothers. Here, we used a rat model to study the potential risks associated with exposure to alcohol and MDMA during pregnancy. Pregnant rats received alcohol, MDMA, or both alcohol and MDMA by gavage at E13 through E15 twice daily. Female offspring treated prenatally with the combination of alcohol and MDMA, but not those exposed to either drug separately, showed at 3 months of age decreased exploratory activity and impaired working memory function. Prenatal treatment with the combination of alcohol and MDMA decreased proliferation of neuronal precursors in the adult dentate gyrus of the hippocampus, as measured by 5-bromo-2-deoxyuridine labelling, and adult neurogenesis, assessed by quantifying doublecortin expression. These results provide the first evidence that the simultaneous abuse of alcohol and ecstasy during pregnancy, even for short periods of time, may cause significant abnormalities in neurocognitive development.

  13. The Effects of Prenatal Alcohol Exposure on Adolescent Cognitive Processing: A Speed-Accuracy Trade-off.

    Science.gov (United States)

    Sampson, Paul D.; Kerr, Beth; Olson, Heather Carmichael; Streissguth, Ann P.; Hunt, Earl; Barr, Helen M.; Bookstein, Fred L.; Thiede, Keith

    1997-01-01

    Aspects of cognitive processing were evaluated for 462 adolescents followed for 14 years. Adolescents had been exposed prenatally to a broad range of maternal drinking, mostly at "social" levels. Alcohol-related deficits on cognitive tasks were summarized by a speed-accuracy trade-off on the spatial-visual reasoning task. (SLD)

  14. Executive Function Predicts Adaptive Behavior in Children with Histories of Heavy Prenatal Alcohol Exposure and Attention Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Ware, Ashley L.; Crocker, Nicole; O’Brien, Jessica W.; Deweese, Benjamin N.; Roesch, Scott C.; Coles, Claire D.; Kable, Julie A.; May, Philip A.; Kalberg, Wendy O.; Sowell, Elizabeth R.; Jones, Kenneth Lyons; Riley, Edward P.; Mattson, Sarah N.

    2011-01-01

    Purpose of Study Prenatal exposure to alcohol often results in disruption to discrete cognitive and behavioral domains, including executive function (EF) and adaptive functioning. In the current study, the relation between these two domains was examined in children with histories of heavy prenatal alcohol exposure, non-exposed children with a diagnosis of attention-deficit/hyperactivity disorder (ADHD), and typically developing controls. Methods As part of a multisite study, three groups of children (8-18y, M = 12.10) were tested: children with histories of heavy prenatal alcohol exposure (ALC, N=142), non-exposed children with ADHD (ADHD, N=82), and typically developing controls (CON, N=133) who did not have ADHD or a history of prenatal alcohol exposure. Children completed subtests of the Delis-Kaplan Executive Function System (D-KEFS) and their primary caregivers completed the Vineland Adaptive Behavior Scales-II (VABS). Data were analyzed using regression analyses. Results Analyses showed that EF measures were predictive of adaptive abilities and significant interactions between D-KEFS measures and group were present. For the ADHD group, the relation between adaptive abilities and EF was more general, with three of the four EF measures showing a significant relation with adaptive score. In contrast, for the ALC group, this relation was specific to the nonverbal EF measures. In the CON group, performance on EF tasks did not predict adaptive scores over the influence of age. Conclusion These results support prior research in ADHD suggesting that EF deficits are predictive of poorer adaptive behavior and extend this finding to include children with heavy prenatal exposure to alcohol. However, the relation between EF and adaptive ability differed by group, suggesting unique patterns of abilities in these children. These results provide enhanced understanding of adaptive deficits in these populations, as well as demonstrate the ecological validity of laboratory

  15. Moderate alcohol exposure compromises neural tube midline development in prenatal brain.

    Science.gov (United States)

    Zhou, Feng C; Sari, Youssef; Powrozek, Teresa; Goodlett, Charles R; Li, Ting-Kai

    2003-08-12

    We previously reported that fetal alcohol treatment compromised the development of the midline raphe and the serotonin neurons contained in it. In this study, we report that the timely development of midline neural tissue during neural tube formation is sensitive to alcohol exposure. Pregnant dams were treated from embryonic day 7 (E7, prior to neurulation) or E8.5 (at neurulation) with the following diets: (a) alcohol (ALC), given as either a 20% or 25% ethanol-derived calorie (EDC) liquid diet, or (b) isocaloric liquid diet pair-fed (PF), or (c) standard rat chow (Chow). Fetal brains from each group were examined on E13, E15, or E18. Neural tube development was compromised as a result of alcohol exposure in the following ways: (1) approximately 60% of embryos at E13 and 20% at E15 showed perforation of the floor plate in the diencephalic vesicle, (2) although completely closed at E13, 70-80% of embryos failed to complete the formation of neural tissue at the roof as the alcohol exposure continued to E15, and (3) 60-80% of embryos show delayed 'occlusion' of the ventral canal by newly formed nestin-positive neuroepithelial cells and S100beta-positive glia in the brainstem of E15. The compromised (incomplete) neural tube midline (cNTM) occurred near the ventricles at E13 and E15, but was later completed at E18. In all cases, the cNTM was accompanied by an enlarged ventricle, and dose-dependent brain weight reduction. The midline of the neural tube at the roof and floor plates is known to mediate timely trophic induction for neural differentiation. Prenatal midline deficits also have the potential to affect the development of midline neurons such as raphe, septal nuclei, and the timely crossing of commissural fibers. The results of the liquid diet alcohol exposure paradigm suggest it is more a model for Alcohol-Related Neurodevelopmental Disorder (ARND) featuring neuropsychiatric disorders than for full-blown fetal alcohol syndrome (FAS) with noticeable facial

  16. Prenatal alcohol exposure and language delay in 2-year-old children: the importance of dose and timing on risk.

    Science.gov (United States)

    O'Leary, Colleen; Zubrick, Stephen R; Taylor, Catherine L; Dixon, Glenys; Bower, Carol

    2009-02-01

    The aim of this study was to investigate the association of dose and timing of prenatal alcohol exposure with early language acquisition. We examined language delay in a randomly selected, population-based sample of Western Australian children born in 1995-1996 whose mothers had agreed to participate in a longitudinal study on health-related behaviors and who had completed the 2-year questionnaire (N = 1739). Information on alcohol consumption was collected at 3 months after birth for four periods; the three months pre-pregnancy and for each trimester separately. Prenatal alcohol exposure was grouped into none, low, moderate-heavy and binge (>5) based on the total quantity consumed per week, quantity consumed per occasion, and frequency of consumption. The communication scale from the Ages & Stages Questionnaire was used to evaluate language delay. Logistic regression analysis was used to generate odds ratios and 95% confidence intervals, adjusted for confounding factors. There was no association between low levels of alcohol consumption and language delay at any time period, although there was a nonsignificant 30% increase in risk when moderate-to-heavy levels of alcohol were consumed in the third trimester. Children exposed to a binge pattern of maternal alcohol consumption in the second trimester had nonsignificant, three-fold increased odds of language delay, with a similar estimate following third trimester alcohol exposure after controlling for covariates. This study did not detect an association between low levels of prenatal alcohol exposure and language delay when compared with women who abstained from alcohol during pregnancy. A nonsignificant threefold increase in the likelihood of language delay was seen in children whose mothers binged during late pregnancy. However, the small numbers of women with a binge-drinking pattern in late pregnancy limited the power of this study; studies analyzing larger numbers of children exposed to binge drinking in late

  17. Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE): Proposed DSM-5 Diagnosis.

    Science.gov (United States)

    Kable, Julie A; O'Connor, Mary J; Olson, Heather Carmichael; Paley, Blair; Mattson, Sarah N; Anderson, Sally M; Riley, Edward P

    2016-04-01

    Over the past 40 years, a significant body of animal and human research has documented the teratogenic effects of prenatal alcohol exposure (PAE). Neurobehavioral Disorder associated with PAE is proposed as a new clarifying term, intended to encompass the neurodevelopmental and mental health symptoms associated with PAE. Defining this disorder is a necessary step to adequately characterize these symptoms and allow clinical assessment not possible using existing physically-based diagnostic schemes. Without appropriate diagnostic guidelines, affected individuals are frequently misdiagnosed and treated inappropriately (often to their considerable detriment) by mental health, educational, and criminal justice systems. Three core areas of deficits identified from the available research, including neurocognitive, self-regulation, and adaptive functioning impairments, are discussed and information regarding associated features and disorders, prevalence, course, familial patterns, differential diagnosis, and treatment of the proposed disorder are also provided.

  18. An evaluation of social skills in children with and without prenatal alcohol exposure.

    Science.gov (United States)

    Rasmussen, C; Becker, M; McLennan, J; Urichuk, L; Andrew, G

    2011-09-01

    The goal of this study was to examine social skills deficits among children with and without prenatal alcohol exposure (PAE) who were both referred to a respite programme. Thirty-seven children with PAE and 23 non-exposed children (aged 3 to 8 years) were evaluated on the Social Skills Rating System (SSRS) by their caregivers and respite workers. As compared with the non-exposed children, those with PAE showed more deficits on caregiver ratings of responsibility, hyperactivity, internalizing problems and overall social skills, as well as respite worker ratings of hyperactivity. The social skills among the PAE group were not related to home placement variables. Among both groups, caregivers rated social skills lower than respite workers, and among the PAE group, girls tended to display more social skills deficits than boys. The SSRS is useful in identifying unique social skills deficits among children with PAE. © 2010 Blackwell Publishing Ltd.

  19. Prevention of congenital defects induced by prenatal alcohol exposure (Conference Presentation)

    Science.gov (United States)

    Sheehan, Megan M.; Karunamuni, Ganga; Pedersen, Cameron J.; Gu, Shi; Doughman, Yong Qiu; Jenkins, Michael W.; Watanabe, Michiko; Rollins, Andrew M.

    2017-02-01

    Over 500,000 women per year in the United States drink during pregnancy, and 1 in 5 of this population also binge drink. Up to 40% of live-born children with prenatal alcohol exposure (PAE) present with congenital heart defects (CHDs) including life-threatening outflow and valvuloseptal anomalies. Previously we established a PAE model in the avian embryo and used optical coherence tomography (OCT) imaging to assay looping-stage (early) cardiac function/structure and septation-stage (late) cardiac defects. Early-stage ethanol-exposed embryos had smaller cardiac cushions (valve precursors) and increased retrograde flow, while late-stage embryos presented with gross head/body defects, and exhibited smaller atrio-ventricular (AV) valves, interventricular septae, and aortic vessels. However, supplementation with the methyl donor betaine reduced gross defects, prevented cardiac defects such as ventricular septal defects and abnormal AV valves, and normalized cardiac parameters. Immunofluorescent staining for 5-methylcytosine in transverse embryo sections also revealed that DNA methylation levels were reduced by ethanol but normalized by co-administration of betaine. Furthermore, supplementation with folate, another methyl donor, in the PAE model appeared to normalize retrograde flow levels which are typically elevated by ethanol exposure. Studies are underway to correlate retrograde flow numbers for folate with associated cushion volumes. Finally, preliminary findings have revealed that glutathione, a key endogenous antioxidant which also regulates methyl group donation, is particularly effective in improving alcohol-impacted survival and gross defect rates. Current investigations will determine whether glutathione has any positive effect on PAE-related CHDs. Our studies could have significant implications for public health, especially related to prenatal nutrition recommendations.

  20. An application of item response theory analysis to alcohol, cannabis, and cocaine criteria in DSM-IV.

    Science.gov (United States)

    Langenbucher, James W; Labouvie, Erich; Martin, Christopher S; Sanjuan, Pilar M; Bavly, Lawrence; Kirisci, Levent; Chung, Tammy

    2004-02-01

    Item response theory (IRT) is supplanting classical test theory as the basis for measures development. This study demonstrated the utility of IRT for evaluating DSM-IV diagnostic criteria. Data on alcohol, cannabis, and cocaine symptoms from 372 adult clinical participants interviewed with the Composite International Diagnostic Interview--Expanded Substance Abuse Module (CIDI-SAM) were analyzed with Mplus (B. Muthen & L. Muthen, 1998) and MULTILOG (D. Thissen, 1991) software. Tolerance and legal problems criteria were dropped because of poor fit with a unidimensional model. Item response curves, test information curves, and testing of variously constrained models suggested that DSM-IV criteria in the CIDI-SAM discriminate between only impaired and less impaired cases and may not be useful to scale case severity. IRT can be used to study the construct validity of DSM-IV diagnoses and to identify diagnostic criteria with poor performance.

  1. Nicotine, alcohol and cocaine coupling to reward processes via endogenous morphine signaling: the dopamine-morphine hypothesis.

    Science.gov (United States)

    Stefano, George B; Bianchi, Enrica; Guarna, Massimo; Fricchione, Gregory L; Zhu, Wei; Cadet, Patrick; Mantione, Kirk J; Casares, Federico M; Kream, Richard M; Esch, Tobias

    2007-06-01

    Pleasure is described as a state or feeling of happiness and satisfaction resulting from an experience that one enjoys. We examine the neurobiological factors underlying reward processes and pleasure phenomena. With regard to possible negative effects of pleasure, we focus on addiction and motivational toxicity. Pleasure can serve cognition, productivity and health, but simultaneously promotes addiction and other negative behaviors. It is a complex neurobiological phenomenon, relying on reward circuitry or limbic activity. These processes involve dopaminergic signaling. Moreover, nicotine, cocaine and alcohol appear to exert their pleasure providing action via endogenous morphinergic mechanisms. Natural rewarding activities are necessary for survival and appetitive motivation, usually governing beneficial biological behaviors like eating, sex and reproduction. Social contacts can further facilitate the positive effects exerted by pleasurable experiences. However, artificial stimulants can be detrimental, since flexibility and normal control of behavior are deteriorated. Additionally, addictive drugs are capable of directly acting on reward pathways, now, in part, via endogenous morphine processes.

  2. Prenatal exposure to vanilla or alcohol induces crawling after these odors in the neonate rat: The role of mu and kappa opioid receptor systems.

    Science.gov (United States)

    Gaztañaga, Mirari; Aranda-Fernández, P Ezequiel; Chotro, M Gabriela

    2015-09-01

    Rat fetuses can perceive chemosensory stimuli derived from their mother's diet, and they may learn about those stimuli. In previous studies we have observed that prenatal exposure to alcohol during the last days of gestation increases the acceptance and liking of an alcohol flavor in infant and adolescent rats. While these results were not found after prenatal exposure to vanilla, cineole or anise, suggesting that the pharmacological properties of alcohol, mediated by the opioid system, underlie the effects observed with this drug. Considering that other studies report enhanced acceptance of non-alcohol flavors experienced prenatally when subjects were tested before infancy, we explore the possibility of observing similar results if testing 1-day old rats exposed prenatally to vanilla. Using an "odor-induced crawling" testing procedure, it was observed that neonates exposed prenatally to vanilla or alcohol crawl for a longer distance towards the experienced odor than to other odors or than control pups. Blocking mu, but not kappa opioid receptors, reduced the attraction of vanilla odor to neonates exposed to vanilla in utero, while the response to alcohol in pups exposed prenatally to this drug was affected by both antagonists. Results confirm that exposure to a non-alcohol odor enhances postnatal responses to it, observable soon after birth, while also suggesting that the mu opioid receptor system plays an important role in generating this effect. The results also imply that with alcohol exposure, the prenatal opioid system is wholly involved, which could explain the longer retention of the enhanced attraction to alcohol following prenatal experience with the drug.

  3. Timing of moderate level prenatal alcohol exposure influences gene expression of sensory processing behavior in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Mary L Schneider

    2009-11-01

    Full Text Available Sensory processing disorder (SPD, characterized by over- or under-responsivity to non-noxious environmental stimuli, is a common but poorly understood disorder. We examined the role of prenatal alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR, and striatal dopamine (DA function on behavioral measures of sensory responsivity to repeated non-noxious sensory stimuli in macaque monkeys. Results indicated that early gestation alcohol exposure induced behavioral under-responsivity to environmental stimuli in monkeys carrying the short (s rh5-HTTLPR allele compared to both early-exposed monkeys homozygous for the long (l allele and monkeys from middle-to-late exposed pregnancies and controls, regardless of genotype. Moreover, prenatal timing of alcohol exposure altered the relationship between sensory scores and DA D2R availability. In early-exposed monkeys, a positive relationship was shown between sensory scores and DA D2R availability, with low or blunted DA function associated with under-responsive sensory function. The opposite pattern was found for the middle-to-late gestation alcohol-exposed group. These findings raise questions about how the timing of prenatal perturbation and genotype contributes to effects on neural processing and possibly alters neural connections.

  4. Biomarkers for detection of prenatal alcohol exposure: a critical review of fatty acid ethyl esters in meconium.

    Science.gov (United States)

    Burd, Larry; Hofer, Ryan

    2008-07-01

    The objective of this study was a review of published studies utilizing measurement of fatty acid ethyl esters (FAEE) in meconium as biomarkers for prenatal alcohol exposure. We completed a literature search of PubMed using the terms meconium, fatty acid ethyl esters, biomarkers, and prenatal alcohol exposure. We included only peer reviewed studies utilizing analysis of meconium for the presence of FAEE in humans through the year 2007. We found 10 articles reporting on original research examining the relationship of FAEE from meconium and prenatal alcohol exposure (PAE). The 10 articles used six different PAE assessment strategies and four different analytical techniques for determining FAEE endpoints. The articles included 2,221 subjects (range 4 to 725) with 455 (20.5%) subjects identified as exposed using the methods stated in the articles. FAEE levels above the studies' respective cutoffs were reported for 502 (22.6%) subjects. The accurate identification of alcohol-exposed pregnancies represents a significant challenge in the development of FAEE detection cutoffs to maximize the sensitivity and specificity of the test. We present several options for the improvement of exposure assessment in future studies of FAEE as biomarkers for PAE. (c) 2008 Wiley-Liss, Inc.

  5. [Prenatal alcohol exposure as an etiological factor in neuropsychiatric diseases of childhood, adolescence and adulthood].

    Science.gov (United States)

    Evrard, Sergio Gustavo

    2010-01-01

    In Argentina, prenatal alcohol exposure (PAE) is an almost neglected condition as an important etiological factor for the induction of a wide spectrum of neuropsychiatric diseases that may appear during childhood, adolescence or adulthood. Children born to alcoholic mothers may show a spectrum of diseases ranging from an apparent normality to a profound mental retardation, passing through epilepsy, attention deficit disorders with or without hyperactivity, autism and pervasive developmental disorders, and different types of learning disorders. When adolescents, they may develop different kinds of personality disorders and substance abuse disorders. Finally, in adulthood, they may suffer from different types of affective and psychotic disorders, among others. A great number of those children may not develop their full mental and social potentiality as free individuals. They usually have diverse types of cognitive, attentional, mnemonic and affective impairments. Not infrequently, they engage in antisocial behaviors, have school or work troubles. In this work, I review the present clinical classifications of the disorders emerging from a PAE and the several neuropsychiatric diseases that can be induced by them, in order to call attention to the Argentinian neuropsychiatric community about the increasingly, although underdiagnosed, frequency of these disorders in our country.

  6. Prenatal alcohol and other early childhood adverse exposures: Direct and indirect pathways to adolescent drinking

    Science.gov (United States)

    Cornelius, Marie D.; De Genna, Natacha M.; Goldschmidt, Lidush; Larkby, Cynthia; Day, Nancy L.

    2016-01-01

    We examined direct and indirect pathways between adverse environmental exposures during gestation and childhood and drinking in mid-adolescence. Mothers and their offspring (n = 917 mother/child dyads) were followed prospectively from second trimester to a 16-year follow-up assessment. Interim assessments occurred at delivery, 6, 10, and 14 years. Adverse environmental factors included gestational exposures to alcohol, tobacco, and marijuana, exposures to childhood maltreatment and violence, maternal psychological symptoms, parenting practices, economic and home environments, and demographic characteristics of the mother and child. Indirect effects of early child behavioral characteristics including externalizing, internalizing activity, attention, and impulsivity were also examined. Polytomous logistic regression analyses were used to evaluate direct effects of adverse environmental exposures with level of adolescent drinking. Structural equation modeling (SEM) was applied to simultaneously estimate the relation between early adversity variables, childhood characteristics, and drinking level at age 16 while controlling for significant covariates. Level of drinking among the adolescent offspring was directly predicted by prenatal exposure to alcohol, less parental strictness, and exposures to maltreatment and violence during childhood. Whites and offspring with older mothers were more likely to drink at higher levels. There was a significant indirect effect between childhood exposure to violence and adolescent drinking via childhood externalizing behavior problems. All other hypothesized indirect pathways were not significant. Thus most of the early adversity measures directly predicted adolescent drinking and did not operate via childhood behavioral dysregulation characteristics. These results highlight the importance of adverse environmental exposures on pathways to adolescent drinking. PMID:26994529

  7. The effects of low to moderate prenatal alcohol exposure in early pregnancy on IQ in 5‐year‐old children

    National Research Council Canada - National Science Library

    Falgreen Eriksen, H‐L; Mortensen, EL; Kilburn, T; Underbjerg, M; Bertrand, J; Støvring, H; Wimberley, T; Grove, J; Kesmodel, US

    2012-01-01

    ..., Støvring H, Wimberley T, Grove J, Kesmodel U. The effects of low to moderate prenatal alcohol exposure in early pregnancy on IQ in 5‐year‐old children. BJOG 2012;119:1191–1200. Objective...

  8. Reductions in alcohol and cocaine use following a group coping intervention for HIV-positive adults with childhood sexual abuse histories.

    Science.gov (United States)

    Meade, Christina S; Drabkin, Anya S; Hansen, Nathan B; Wilson, Patrick A; Kochman, Arlene; Sikkema, Kathleen J

    2010-11-01

    Few interventions exist to reduce alcohol and non-injection drug use among people living with HIV/AIDS. This study tested the effects of a coping group intervention for HIV-positive adults with childhood sexual abuse histories on alcohol, cocaine and marijuana use. Participants were assigned randomly to the experimental coping group or a time-matched comparison support group. Both interventions were delivered in a group format over 15 weekly 90-minute sessions. A diverse sample of 247 HIV-positive men and women with childhood sexual abuse were recruited from AIDS service organizations and community health centers in New York City. Substance use was assessed pre- and post-intervention and every 4 months during a 12-month follow-up period. Using an intent-to-treat analysis, longitudinal changes in substance use by condition were assessed using generalized estimating equations. At baseline, 42% of participants drank alcohol, 26% used cocaine and 26% used marijuana. Relative to participants in the support group, those in the coping group had greater reductions in quantity of alcohol use (Wald χ²(₄)=10.77, P = 0.029) and any cocaine use (Wald χ²(₄) = 9.81, P = 0.044) overtime. Many HIV patients, particularly those with childhood sexual abuse histories, continue to abuse substances. This group intervention that addressed coping with HIV and sexual trauma was effective in reducing alcohol and cocaine use, with effects sustained at 12-month follow-up. Integrating mental health treatment into HIV prevention may improve outcomes. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.

  9. Associations of the 5-hydroxytryptamine (serotonin) receptor 1B gene (HTR1B) with alcohol, cocaine, and heroin abuse.

    Science.gov (United States)

    Cao, Jian; LaRocque, Emily; Li, Dawei

    2013-03-01

    Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders including alcohol and drug dependence (abuse). The human 5-hydroxytryptamine (serotonin) receptor 1B, encoded by the HTR1B (5-HT1B) gene, is a presynaptic serotonin autoreceptor that plays an important role in regulating serotonin synthesis and release. Although there was evidence of associations of the HTR1B gene variants in the etiologies of substance use disorders, negative findings were also reported. To clarify the roles of commonly reported single nucleotide polymorphisms (SNPs) of the HTR1B gene underlying alcohol and drug dependence (abuse), we performed a meta-analysis based on the available genotype data from individual candidate gene-based association studies. Evidence of association was found between the functional SNP -161A>T (rs130058) and alcohol, cocaine, and heroin dependence (e.g., P = 0.03 and odds ratio (OR) = 1.2 (1.02, 1.42) in the combined European, Asian, African, and Hispanic populations). SNP -261T>G (rs11568817) also showed evidence of association but with different directions in Europeans and non-Europeans (e.g., P = 0.0018 with OR = 1.42 (1.14, 1.76) and P = 0.01 with ORs = 0.5 (0.3, 0.85), respectively). This meta-analysis supports the associations of HTR1B -261T>G and -161A>T with alcohol and drug abuse and further investigations are warranted in larger samples.

  10. Low dose prenatal alcohol exposure does not impair spatial learning and memory in two tests in adult and aged rats.

    Directory of Open Access Journals (Sweden)

    Carlie L Cullen

    Full Text Available Consumption of alcohol during pregnancy can have detrimental impacts on the developing hippocampus, which can lead to deficits in learning and memory function. Although high levels of alcohol exposure can lead to severe deficits, there is a lack of research examining the effects of low levels of exposure. This study used a rat model to determine if prenatal exposure to chronic low dose ethanol would result in deficits in learning and memory performance and if this was associated with morphological changes within the hippocampus. Sprague Dawley rats were fed a liquid diet containing 6% (vol/vol ethanol (EtOH or an isocaloric control diet throughout gestation. Male and Female offspring underwent behavioural testing at 8 (Adult or 15 months (Aged of age. Brains from these animals were collected for stereological analysis of pyramidal neuron number and dendritic morphology within the CA1 and CA3 regions of the dorsal hippocampus. Prenatal ethanol exposed animals did not differ in spatial learning or memory performance in the Morris water maze or Y maze tasks compared to Control offspring. There was no effect of prenatal ethanol exposure on pyramidal cell number or density within the dorsal hippocampus. Overall, this study indicates that chronic low dose prenatal ethanol exposure in this model does not have long term detrimental effects on pyramidal cells within the dorsal hippocampus or impair spatial learning and memory performance.

  11. Toward a global view of alcohol, tobacco, cannabis, and cocaine use: findings from the WHO World Mental Health Surveys.

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    Louisa Degenhardt

    2008-07-01

    Full Text Available BACKGROUND: Alcohol, tobacco, and illegal drug use cause considerable morbidity and mortality, but good cross-national epidemiological data are limited. This paper describes such data from the first 17 countries participating in the World Health Organization's (WHO's World Mental Health (WMH Survey Initiative. METHODS AND FINDINGS: Household surveys with a combined sample size of 85,052 were carried out in the Americas (Colombia, Mexico, United States, Europe (Belgium, France, Germany, Italy, Netherlands, Spain, Ukraine, Middle East and Africa (Israel, Lebanon, Nigeria, South Africa, Asia (Japan, People's Republic of China, and Oceania (New Zealand. The WHO Composite International Diagnostic Interview (CIDI was used to assess the prevalence and correlates of a wide variety of mental and substance disorders. This paper focuses on lifetime use and age of initiation of tobacco, alcohol, cannabis, and cocaine. Alcohol had been used by most in the Americas, Europe, Japan, and New Zealand, with smaller proportions in the Middle East, Africa, and China. Cannabis use in the US and New Zealand (both 42% was far higher than in any other country. The US was also an outlier in cocaine use (16%. Males were more likely than females to have used drugs; and a sex-cohort interaction was observed, whereby not only were younger cohorts more likely to use all drugs, but the male-female gap was closing in more recent cohorts. The period of risk for drug initiation also appears to be lengthening longer into adulthood among more recent cohorts. Associations with sociodemographic variables were consistent across countries, as were the curves of incidence of lifetime use. CONCLUSIONS: Globally, drug use is not distributed evenly and is not simply related to drug policy, since countries with stringent user-level illegal drug policies did not have lower levels of use than countries with liberal ones. Sex differences were consistently documented, but are decreasing in more

  12. The Maternal Lifestyle Study: Sleep Problems in Children with Prenatal Substance Exposure

    Science.gov (United States)

    Stone, Kristen C.; LaGasse, Linda L.; Lester, Barry M.; Shankaran, Seetha; Bada, Henrietta S.; Bauer, Charles R.; Hammond, Jane A.

    2010-01-01

    Objective To examine the relationships between sleep problems and prenatal exposure to cocaine, opiates, marijuana, alcohol, and nicotine in children 1 month to 12 years of age. Design Sleep data was collected by maternal report in a prospective longitudinal follow-up of children participating in the Maternal Lifestyle multisite study. Setting Hospital based research centers in Providence, RI, Miami, FL, Detroit, MI, and Memphis, TN Participants There were 808 participants: 374 exposed to cocaine and/or opiates; 434 comparison. Main exposure Prenatal cocaine, opiate, marijuana, alcohol, and nicotine exposure. Outcome measure Sleep problems in early, middle, and late childhood, assessed as composites of maternal report items. Results Of the five substances, prenatal nicotine exposure was the only unique predictor of sleep problems (B = .074, R2 Δ = .008, p = .012) with adjustment for covariates including SES, marital status, physical abuse, prenatal medical care, and postnatal cigarette smoke exposure. Conclusion Prenatal exposure to nicotine was positively associated with children's sleep problems persisting throughout the first 12 years of life. Targeting this group of children for educational and behavioral efforts to prevent and treat sleep problems is merited given that good sleep may serve as a protective factor for other developmental outcomes. PMID:20439796

  13. [Subtypes of cocaine addicts with and without associated problematic alcohol use: towards a neuropsychology of personality applied to clinical practice].

    Science.gov (United States)

    Pedrero Pérez, Eduardo J; Ruiz Sánchez de León, José M

    2012-01-01

    It is important to know which personality factors are associated with addiction so to distinguish addicts that require specialized treatment from those who do not, and to identify those addicts who achieve abstinence from those who continue their substance use despite the negative consequences. Cloninger's model includes biological and psychosocial variables that can be characterized in neuropsychological terms. Two samples were analyzed: individuals who had begun cocaine addiction treatment (n=183) and a non-clinical population sample (n = 183), matched for sex, age and educational level. Alcohol abuse/dependence was monitored as an independent variable. Significant differences and large effect size were found between addicts and non-clinical population in Novelty Seeking and Self-Directedness, and to a lesser extent, in Harm Avoidance. These differences increase when problematic use of alcohol is added. According to the profile of traits, clusters of addicts were established and differences were obtained in variables such as functional/dysfunctional impulsivity, dysexecutive symptoms and perceived stress. Six clusters were identified, some of minor severity, the most severely problematic clusters being characterized by higher levels of dysfunctional impulsivity, more dysexecutive symptoms and higher levels of perceived stress. Self-Directedness seems to reflect the deficit of prefrontal systems in the regulation of behavior, as well as in emotion and impulse control. It is proposed that evaluation of the personality is more useful than the mere assessment of symptoms for classifying addicts, determining their needs and designing a therapeutic itinerary.

  14. Prenatal alcohol exposure alters expression of neurogenesis-related genes in an ex vivo cell culture model.

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    Tyler, Christina R; Allan, Andrea M

    2014-08-01

    Prenatal alcohol exposure can lead to long-lasting changes in functional and genetic programs of the brain, which may underlie behavioral alterations seen in Fetal Alcohol Spectrum Disorder (FASD). Aberrant fetal programming during gestational alcohol exposure is a possible mechanism by which alcohol imparts teratogenic effects on the brain; however, current methods used to investigate the effects of alcohol on development often rely on either direct application of alcohol in vitro or acute high doses in vivo. In this study, we used our established moderate prenatal alcohol exposure (PAE) model, resulting in maternal blood alcohol content of approximately 20 mM, and subsequent ex vivo cell culture to assess expression of genes related to neurogenesis. Proliferating and differentiating neural progenitor cell culture conditions were established from telencephalic tissue derived from embryonic day (E) 15-17 tissue exposed to alcohol via maternal drinking throughout pregnancy. Gene expression analysis on mRNA derived in vitro was performed using a microarray, and quantitative PCR was conducted for genes to validate the microarray. Student's t tests were performed for statistical comparison of each exposure under each culture condition using a 95% confidence interval. Eleven percent of genes on the array had significantly altered mRNA expression in the prenatal alcohol-exposed neural progenitor culture under proliferating conditions. These include reduced expression of Adora2a, Cxcl1, Dlg4, Hes1, Nptx1, and Vegfa and increased expression of Fgf13, Ndn, and Sox3; bioinformatics analysis indicated that these genes are involved in cell growth and proliferation. Decreased levels of Dnmt1 and Dnmt3a were also found under proliferating conditions. Under differentiating conditions, 7.3% of genes had decreased mRNA expression; these include Cdk5rap3, Gdnf, Hey2, Heyl, Pard6b, and Ptn, which are associated with survival and differentiation as indicated by bioinformatics analysis

  15. Changes in health professionals' knowledge, attitudes and practice following provision of educational resources about prevention of prenatal alcohol exposure and fetal alcohol spectrum disorder.

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    Payne, Janet; France, Kathryn; Henley, Nadine; D'Antoine, Heather; Bartu, Anne; O'Leary, Colleen; Elliott, Elizabeth; Bower, Carol

    2011-07-01

    We provided health professionals in Western Australia (WA) with educational resources about prevention of prenatal alcohol exposure and fetal alcohol spectrum disorder and assessed changes in their knowledge, attitudes and practice concerning fetal alcohol syndrome (FAS) and alcohol consumption in pregnancy. Following our 2002 survey of health professionals in WA, we developed and distributed educational resources to 3348 health professionals in WA in 2007. Six months later we surveyed 1483 of these health professionals. Prevalence rate ratios [PRR] and 95% confidence intervals [CI] were calculated to compare 2007 results with results from the 2002 survey. Of the 1001 responding health professionals, 69.8% had seen the educational resources; of these 77.1% have used them and 48.5% said the resources had assisted them to change their practice or their intention to change their practice. Compared with 2002, there was an increase in the proportion who knew all the essential features of FAS from 11.7% to 15.8% [PRR 1.35; 95% CI 1.09, 1.67] and had diagnosed FAS, from 4.8% to 7.3% [PRR 1.52; 95% CI 1.08, 2.13]. In 2007, 98.1% of health professionals stated they would advise pregnant women to consider not drinking at all or advise them that no alcohol in pregnancy is the safest choice. Health professionals surveyed in 2007 have increased their knowledge, changed their attitudes and practice about FAS, and altered the advice they give to pregnant women about alcohol consumption since our survey in 2002. It is essential that we build on this change and continue to support health professionals' knowledge, attitudes and practice about the prevention of prenatal alcohol exposure and fetal alcohol spectrum disorder. The educational resources for health professionals may be ordered as hard copies and downloaded from the internet http://www.ichr.uwa.edu.au/alcoholandpregnancy.

  16. Temperament and character traits associated with the use of alcohol, cannabis, cocaine, benzodiazepines, and hallucinogens: evidence from a large Brazilian web survey

    Directory of Open Access Journals (Sweden)

    Ricardo Schneider Jr.

    2015-03-01

    Full Text Available Objectives: To evaluate how personality traits are associated with occasional use, abuse, and dependence of alcohol, cannabis, cocaine, benzodiazepines, and hallucinogens in a large availability sample of adults via online questionnaires. Methods: The sample consisted of 8,646 individuals (24.7% men and 75.3% women who completed an anonymous web survey. Involvement with drugs and temperament/character traits were assessed through the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST and the Temperament and Character Inventory - Revised (TCI-R, respectively. Interactions among variables were analyzed using MANOVA with Bonferroni adjustment. Results: Novelty seeking was the trait most associated with increased involvement with alcohol, cannabis, and cocaine. There was a significant association between harm avoidance and benzodiazepine use. Persistence was lower in cannabis-, benzodiazepine-, and cocaine-dependent subjects, as well as in hallucinogen abusers. Self-directedness was reduced in dependents of all drug classes. No strong relationships were found between other temperament or character dimensions and the severity of drug use. Conclusions: Novelty seeking was associated with increased involvement with all drugs studied in this sample, although to a lesser extent with benzodiazepines and hallucinogens. The temperament and character profile for benzodiazepine use was different from that of other drugs due to the relationship with higher harm avoidance and self-transcendence and lower self-directedness.

  17. Health-related quality of life of Canadian children and youth prenatally exposed to alcohol

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    Ungar Wendy J

    2006-10-01

    Full Text Available Abstract Background In Canada, the incidence of Fetal Alcohol Spectrum Disorder (FASD has been estimated to be 1 in 100 live births. Caused by prenatal exposure to alcohol, FASD is the leading cause of neuro-developmental disabilities among Canadian children, and youth. Objective: To measure the health-related quality of life (HRQL of Canadian children and youth diagnosed with FASD. Methods A prospective cross-sectional study design was used. One-hundred and twenty-six (126 children and youth diagnosed with FASD, aged 8 to 21 years, living in urban and rural communities throughout Canada participated in the study. Participants completed the Health Utilities Index Mark 3 (HUI3. HUI3 measures eight health attributes: vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain. Utilities were used to measure a single cardinal value between 0 and 1.0 (0 = all-worst health state; 1 = perfect health to reflect the global HRQL for that child. Mean HRQL scores and range of scores of children and youth with FASD were calculated. A one-sample t-test was used to compare mean HRQL scores of children and youth with FASD to those from the Canadian population. Results Mean HRQL score of children and youth with FASD was 0.47 (95% CI: 0.42 to 0.52 as compared to a mean score of 0.93 (95% CI: 0.92 to 0.94 in those from the general Canadian population (p Conclusion Children and youth with FASD have significantly lower HRQL than children and youth from the general Canadian population. This finding has significant implications for practice, policy development, and research.

  18. Betaine supplementation reduces congenital defects after prenatal alcohol exposure (Conference Presentation)

    Science.gov (United States)

    Karunamuni, Ganga; Gu, Shi; Doughman, Yong Qiu; Sheehan, Megan M.; Ma, Pei; Peterson, Lindsy M.; Linask, Kersti K.; Jenkins, Michael W.; Rollins, Andrew M.; Watanabe, Michiko

    2016-03-01

    Over 500,000 women per year in the United States drink during pregnancy, and 1 in 5 of this population also binge drink. As high as 20-50% of live-born children with prenatal alcohol exposure (PAE) present with congenital heart defects including outflow and valvuloseptal anomalies that can be life-threatening. Previously we established a model of PAE (modeling a single binge drinking episode) in the avian embryo and used optical coherence tomography (OCT) imaging to assay early-stage cardiac function/structure and late-stage cardiac defects. At early stages, alcohol/ethanol-exposed embryos had smaller cardiac cushions and increased retrograde flow. At late stages, they presented with gross morphological defects in the head and chest wall, and also exhibited smaller or abnormal atrio-ventricular (AV) valves, thinner interventricular septae (IVS), and smaller vessel diameters for the aortic trunk branches. In other animal models, the methyl donor betaine (found naturally in many foods such as wheat bran, quinoa, beets and spinach) ameliorates neurobehavioral deficits associated with PAE but the effects on heart structure are unknown. In our model of PAE, betaine supplementation led to a reduction in gross structural defects and appeared to protect against certain types of cardiac defects such as ventricular septal defects and abnormal AV valvular morphology. Furthermore, vessel diameters, IVS thicknesses and mural AV leaflet volumes were normalized while the septal AV leaflet volume was increased. These findings highlight the importance of betaine and potentially methylation levels in the prevention of PAE-related birth defects which could have significant implications for public health.

  19. Neurocircuitry underlying stress and emotional regulation in animals prenatally exposed to alcohol and subjected to chronic mild stress in adulthood

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    Charlis eRaineki

    2014-02-01

    Full Text Available Individuals exposed to alcohol during gestation show higher rates of psychopathologies. The hyperresponsivity to stress induced by prenatal alcohol exposure may be related to this increased rate of psychopathologies, especially because this population is more likely to be exposed to stressful environments throughout life. However, alcohol-induced changes in the overlapping neurocircuitries that underlie stress and the expression of psychopathologies are not fully understood. Here, we performed a comprehensive analysis of the neural activity within central areas known to play key roles in both emotional and stress regulation. Adult male and female offspring from prenatal alcohol exposure (PAE, pair-fed, and ad libitum-fed control conditions were exposed to chronic mild stress (CMS. Following CMS, the neural activity (c-fos mRNA of the amygdala, ventral hippocampal formation, medial prefrontal cortex (mPFC, and paraventricular nucleus of hypothalamus (PVN was assessed in response to an acute stress (elevated plus maze. Our results demonstrate that, overall, PAE decreased neural activity within the amygdala and hippocampal formation in males and increased neural activity within the amygdala and mPFC in females. CMS reduced neural activity within the mPFC and PVN in PAE males, but reduced activity in all areas analyzed in control males. By contrast, CMS reduced neural activity in the mPFC in PAE females and had no effects in control females. Furthermore, the constrained principal component analysis revealed that these patterns of neural activity resulted in differential activation of functional neural networks in males compared to females, indicating sexually dimorphic effects of PAE and CMS. Importantly, the altered networks of brain activation in PAE animals may underlie the hyperresponsivity to stress and increased psychopathologies observed among individuals prenatally exposed to alcohol.

  20. Maternal L-glutamine supplementation prevents prenatal alcohol exposure-induced fetal growth restriction in an ovine model.

    Science.gov (United States)

    Sawant, Onkar B; Wu, Guoyao; Washburn, Shannon E

    2015-06-01

    Prenatal alcohol exposure is known to cause fetal growth restriction and disturbances in amino acid bioavailability. Alterations in these parameters can persist into adulthood and low birth weight can lead to altered fetal programming. Glutamine has been associated with the synthesis of other amino acids, an increase in protein synthesis and it is used clinically as a nutrient supplement for low birth weight infants. The aim of this study was to explore the effect of repeated maternal alcohol exposure and L-glutamine supplementation on fetal growth and amino acid bioavailability during the third trimester-equivalent period in an ovine model. Pregnant sheep were randomly assigned to four groups, saline control, alcohol (1.75-2.5 g/kg), glutamine (100 mg/kg, three times daily) or alcohol + glutamine. In this study, a weekend binge drinking model was followed where treatment was done 3 days per week in succession from gestational day (GD) 109-132 (normal term ~147). Maternal alcohol exposure significantly reduced fetal body weight, height, length, thoracic girth and brain weight, and resulted in decreased amino acid bioavailability in fetal plasma and placental fluids. Maternal glutamine supplementation successfully mitigated alcohol-induced fetal growth restriction and improved the bioavailability of glutamine and glutamine-related amino acids such as glycine, arginine, and asparagine in the fetal compartment. All together, these findings show that L-glutamine supplementation enhances amino acid availability in the fetus and prevents alcohol-induced fetal growth restriction.

  1. Prenatal exposure to alcohol does not affect radial maze learning and hippocampal mossy fiber sizes in three inbred strains of mouse

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    Bertholet Jean-Yves

    2005-04-01

    Full Text Available Abstract Background The aim of this study was to investigate the effects of prenatal alcohol exposure on radial-maze learning and hippocampal neuroanatomy, particularly the sizes of the intra- and infrapyramidal mossy fiber (IIPMF terminal fields, in three inbred strains of mice (C57BL/6J, BALB/cJ, and DBA/2J. Results Although we anticipated a modification of both learning and IIPMF sizes, no such effects were detected. Prenatal alcohol exposure did, however, interfere with reproduction in C57BL/6J animals and decrease body and brain weight (in interaction with the genotype at adult age. Conclusion Prenatal alcohol exposure influenced neither radial maze performance nor the sizes of the IIPMF terminal fields. We believe that future research should be pointed either at different targets when using mouse models for Fetal Alcohol Syndrome (e.g. more complicated behavioral paradigms, different hippocampal substructures, or other brain structures or involve different animal models.

  2. Effects of endogenous and exogenous progesterone on emotional intelligence in cocaine dependent men and women who also abuse alcohol

    Science.gov (United States)

    Milivojevic, V; Sinha, R; Morgan, PT; Sofuoglu, M; Fox, HC

    2015-01-01

    Objective As sex differences in substance dependence may impinge upon the perception and regulation of emotion, we assess Emotional Intelligence (EI) as a function of gender, menstrual cycle (MC) phase and hormonal changes in early abstinent cocaine dependent individuals who abuse alcohol (CDA). Methods Study 1: The Mayer, Salovey, and Caruso Emotional Intelligence Test (MSCEIT) was administered to 98 CDA (55M/43F) and 56 healthy (28M/28F) individuals. Performance in women was also assessed by MC phase. Study 2: The MSCEIT was administered to 18 CDA (19M/9F) who received exogenous progesterone (400mg/day) versus placebo for 7 days. (Study 2). Results Study 1: Healthy females were better than healthy males at facilitating thought and managing emotions. This gender discrepancy was not observed in the CDA group. Additionally, all women in the high compared with the low progesterone phase of their MC were better at managing their emotions. Study 2: Exogenous progesterone improved ability to facilitate thought in both males and females. Conclusions CDA women may be vulnerable to difficulties managing and regulating emotions. Gonadal hormones may contribute to this gender effect, as increases in both endogenous and exogenous progesterone improved selective aspects of EI. PMID:25363303

  3. Effects of endogenous and exogenous progesterone on emotional intelligence in cocaine-dependent men and women who also abuse alcohol.

    Science.gov (United States)

    Milivojevic, Verica; Sinha, Rajita; Morgan, Peter T; Sofuoglu, Mehmet; Fox, Helen C

    2014-11-01

    As sex differences in substance dependence may impinge upon the perception and regulation of emotion, we assess emotional intelligence (EI) as a function of gender, menstrual cycle (MC) phase and hormonal changes in early abstinent cocaine-dependent individuals who abuse alcohol (CDA). Study 1: The Mayer, Salovey, and Caruso Emotional Intelligence Test (MSCEIT) was administered to 98 CDA (55 M/43 F) and 56 healthy (28 M/28 F) individuals. Performance in women was also assessed by MC phase. Study 2: The MSCEIT was administered to 28 CDA (19 M/9 F) who received exogenous progesterone (400 mg/day) versus placebo for 7 days (study 2). Study 1: Healthy females were better than healthy males at facilitating thought and managing emotions. This gender discrepancy was not observed in the CDA group. Additionally, all women in the high compared with the low progesterone phase of their MC were better at managing their emotions. Study 2: Exogenous progesterone improved ability to facilitate thought in both males and females. CDA women may be vulnerable to difficulties managing and regulating emotions. Gonadal hormones may contribute to this gender effect, as increases in both endogenous and exogenous progesterone improved selective aspects of EI. Copyright © 2014 John Wiley & Sons, Ltd.

  4. The impact of sensory integration therapy on gross motor function in children after prenatal exposure to alcohol

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    Jacek Wilczyński

    2015-03-01

    Full Text Available Introduction : In Poland there are 900 cases of full-blown foetal alcohol syndrome (FAS in neonates per year, and in 9000 children there are some symptoms of it. Aim of the research : To analyse the impact of sensory integration (SI therapy on gross motor skills function in children after prenatal exposure to alcohol. Material and methods: The study was conducted on a group of 20 children aged 4–5 years with information from an interview about prenatal exposure to alcohol. The diagnosis of sensory integration disorder consisted of two 60-minute diagnostics meetings. Twelve trials with clinical observations were performed by Ayres: finger to nose, cocontraction, prone extension posture, flexed position supine, asymmetrical tonic neck reflex (ATOS, symmetrical tonic neck reflex (STOS, muscle tension, Schilder test, dynamic balance, static balance, gravitational insecurity, and trunk stabilisation. The therapeutic program included: normalisation of the vestibular and proprioceptive system, normalisation of the touch system, strengthening muscle tension, development of motion planning, development of oculomotor performance, development of motor coordination, hand therapy, integration of ATOS, STOS, development of locomotion and balance functions, and improving efficiency of gross and small motor skills. Results and conclusions : High efficiency of SI therapy has been shown in children after prenatal exposure to alcohol on the example of gross motor skills. Positive effects of SI therapy have been shown for tests: finger to nose, in the erect position on the stomach, the flexural position on the back, ATOS, STOS, Schilder test, dynamic balance, static balance, and the uncertainty of gravity and trunk stabilisation. Only cocontraction and muscle tension tests showed no efficacy of SI therapy. The a-Cronbach position analysis showed high reliability of the performed tests both before and after the therapy. It is advisable to continue the study on a

  5. Effect of prenatal alcohol exposure on childhood academic outcomes: contrasting maternal and paternal associations in the ALSPAC study.

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    Rosa Alati

    Full Text Available The impact of low-to-moderate levels of alcohol consumption during pregnancy on child cognitive outcomes has been of recent concern. This study has tested the hypothesis that low-to-moderate maternal alcohol use in pregnancy is associated with lower school test scores at age 11 in the offspring via intrauterine mechanisms.We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC, a birth cohort study based in the South West of England. Analyses were conducted on 7062 participants who had complete data on: maternal and paternal patterns of alcohol use in the first trimester and at 18 weeks' gestation, child's academic outcomes measured at age 11, gender, maternal age, parity, marital status, ethnicity, household crowding, home ownership status and parental education. We contrasted the association of mother's alcohol consumption during pregnancy with child's National Curriculum Key Stage 2 (KS2 test scores with the association for father's alcohol consumption (during the time the mother was pregnant with child's National Curriculum Key Stage 2 (KS2 test scores. We used multivariate linear regression to estimate mean differences and 95% confidence intervals [CI] in KS2 scores across the exposure categories and computed f statistics to compare maternal and paternal associations.Drinking up to 1 unit of alcohol a day during pregnancy was not associated with lower test scores. However, frequent prenatal consumption of 4 units (equivalent to 32 grams of alcohol on each single drinking occasion was associated with reduced educational attainment [Mean change in offspring KS2 score was -0.68 (-1.03, -0.33 for maternal alcohol categories compared to 0.27 (0.07, 0.46 for paternal alcohol categories]. Frequent consumption of 4 units of alcohol during pregnancy may adversely affect childhood academic outcomes via intrauterine mechanisms.

  6. Dysregulation of the cortisol diurnal rhythm following prenatal alcohol exposure and early life adversity.

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    McLachlan, Kaitlyn; Rasmussen, Carmen; Oberlander, Tim F; Loock, Christine; Pei, Jacqueline; Andrew, Gail; Reynolds, James; Weinberg, Joanne

    2016-06-01

    The hypothalamic-pituitary-adrenal (HPA) axis is impacted by a multitude of pre- and postnatal factors. Developmental programming of HPA axis function by prenatal alcohol exposure (PAE) has been demonstrated in animal models and in human infants, but remains understudied in older children and adolescents. Moreover, early life adversity (ELA), which occurs at higher rates in children with PAE than in non-exposed children, may also play a role in programming the stress response system. In a cohort of children and adolescents with PAE and ELA (PAE + ELA), we evaluated HPA function through assessment of diurnal cortisol activity compared to that in typically developing controls, as well as the associations among specific ELAs, adverse outcomes, protective factors, and diurnal cortisol. Morning and evening saliva samples were taken under basal conditions from 42 children and adolescents (5-18 years) with PAE + ELA and 43 typically developing controls. High rates of ELA were shown among children with PAE, and significantly higher evening cortisol levels and a flatter diurnal slope were observed in children with PAE + ELA, compared to controls. Medication use in the PAE + ELA group was associated with lower morning cortisol levels, which were comparable to controls. Complex associations were found among diurnal cortisol patterns in the PAE + ELA group and a number of ELAs and later adverse outcomes, whereas protective factors were associated with more typical diurnal rhythms. These results complement findings from research on human infants and animal models showing dysregulated HPA function following PAE, lending weight to the suggestion that PAE and ELA may interact to sensitize the developing HPA axis. The presence of protective factors may buffer altered cortisol regulation, underscoring the importance of early assessment and interventions for children with FASD, and in particular, for the many children with FASD who also have ELA.

  7. A case story, involving the use of maltitol, a sugar alcohol, as a cutting agent in amphetamine and cocaine powders

    DEFF Research Database (Denmark)

    Reitzel, Lotte Ask; Holm, Niels Bjerre; Linnet, Kristian

    2016-01-01

    In a criminal case involving cutting and resale of amphetamine and cocaine in the Copenhagen area of Denmark, maltitol was used as a cutting agent. The analysis of maltitol in seizures of pure diluents as well as in amphetamine and cocaine powders was carried out using reversed-phase high perform...

  8. Prenatal alcohol exposure modifies glucocorticoid receptor subcellular distribution in the medial prefrontal cortex and impairs frontal cortex-dependent learning.

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    Andrea M Allan

    Full Text Available Prenatal alcohol exposure (PAE has been shown to impair learning, memory and executive functioning in children. Perseveration, or the failure to respond adaptively to changing contingencies, is a hallmark on neurobehavioral assessment tasks for human fetal alcohol spectrum disorder (FASD. Adaptive responding is predominantly a product of the medial prefrontal cortex (mPFC and is regulated by corticosteroids. In our mouse model of PAE we recently reported deficits in hippocampal formation-dependent learning and memory and a dysregulation of hippocampal formation glucocorticoid receptor (GR subcellular distribution. Here, we examined the effect of PAE on frontal cortical-dependent behavior, as well as mPFC GR subcellular distribution and the levels of regulators of intracellular GR transport. PAE mice displayed significantly reduced response flexibility in a Y-maze reversal learning task. While the levels of total nuclear GR were reduced in PAE mPFC, levels of GR phosphorylated at serines 203, 211 and 226 were not significantly changed. Cytosolic, but not nuclear, MR levels were elevated in the PAE mPFC. The levels of critical GR trafficking proteins, FKBP51, Hsp90, cyclophilin 40, dynamitin and dynein intermediate chain, were altered in PAE mice, in favor of the exclusion of GR from the nucleus, indicating dysregulation of GR trafficking. Our findings suggest that there may be a link between a deficit in GR nuclear localization and frontal cortical learning deficits in prenatal alcohol-exposed mice.

  9. Crash Culpability Relative to Age and Sex for Injured Drivers Using Alcohol, Marijuana or Cocaine

    OpenAIRE

    Soderstrom, Carl A.; Dischinger, Patricia C; Kufera, Joseph A.; Ho, Shiu M.; Shepard, Angela

    2005-01-01

    While there is a great deal of data documenting the etiologic role alcohol use plays in crash culpability, there is a dearth of data for other drugs. The purpose of this study was to assess crash culpability for single drug use among injured drivers admitted to a regional trauma center. This study is the largest of its kind involving trauma center patients. Clinical toxicology results obtained for patient care were linked to police crash reports containing a field attributing crash culpabilit...

  10. Metabolomics of cocaine: implications in toxicity.

    Science.gov (United States)

    Dinis-Oliveira, Ricardo Jorge

    2015-01-01

    Cocaine is the most commonly used illicit drug among those seeking care in Emergency Departments or drug detoxification centers. Cocaine, chemically known as benzoylmethylecgonine, is a naturally occurring substance found in the leaves of the Erythroxylum coca plant. The pharmacokinetics of cocaine is dependent on multiple factors, such as physical/chemical form, route of administration, genetics and concurrent consumption of alcohol. This review aims to discuss metabolomics of cocaine, namely by presenting all known metabolites of cocaine and their roles in the cocaine-mediated toxic effects.

  11. Prenatal drug exposure affects neonatal brain functional connectivity.

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    Salzwedel, Andrew P; Grewen, Karen M; Vachet, Clement; Gerig, Guido; Lin, Weili; Gao, Wei

    2015-04-01

    Prenatal drug exposure, particularly prenatal cocaine exposure (PCE), incurs great public and scientific interest because of its associated neurodevelopmental consequences. However, the neural underpinnings of PCE remain essentially uncharted, and existing studies in school-aged children and adolescents are confounded greatly by postnatal environmental factors. In this study, leveraging a large neonate sample (N = 152) and non-invasive resting-state functional magnetic resonance imaging, we compared human infants with PCE comorbid with other drugs (such as nicotine, alcohol, marijuana, and antidepressant) with infants with similar non-cocaine poly drug exposure and drug-free controls. We aimed to characterize the neural correlates of PCE based on functional connectivity measurements of the amygdala and insula at the earliest stage of development. Our results revealed common drug exposure-related connectivity disruptions within the amygdala-frontal, insula-frontal, and insula-sensorimotor circuits. Moreover, a cocaine-specific effect was detected within a subregion of the amygdala-frontal network. This pathway is thought to play an important role in arousal regulation, which has been shown to be irregular in PCE infants and adolescents. These novel results provide the earliest human-based functional delineations of the neural-developmental consequences of prenatal drug exposure and thus open a new window for the advancement of effective strategies aimed at early risk identification and intervention.

  12. Alcohol use, injuries, and prenatal visits during three successive pregnancies among American Indian women on the Northern Plains who have children with fetal alcohol syndrome or incomplete fetal alcohol syndrome.

    Science.gov (United States)

    Kvigne, Valborg L; Leonardson, Gary R; Borzelleca, Joseph; Brock, Ellen; Neff-Smith, Martha; Welty, Thomas K

    2008-07-01

    The purpose of the study was to compare three sequential pregnancies of American Indian women who have children with FAS or children with incomplete FAS with women who did not have children with FAS. Two retrospective case-control studies were conducted of Northern Plains American Indian children with fetal alcohol syndrome (FAS) (Study 1) or incomplete FAS (Study 2) in 1981-1993. Three successive pregnancies ending in live births of 43 case mothers who had children with FAS, and 35 case mothers who had children with incomplete FAS were compared to the pregnancies of 86 and 70 control mothers who did not have children with FAS, respectively, in the two studies. Prenatal records were abstracted for the index child (child with FAS or incomplete FAS) and siblings born just before and just after the index child, and comparable prenatal records for the controls. Compared to the controls, significantly more case mothers used alcohol before and after all three pregnancies and during pregnancy with the before sibling and the index child. Mothers who had children with FAS reduced their alcohol use during the pregnancy following the birth of the index child. All Study 1 case mothers (100%) and 60% of Study 2 case mothers used alcohol during the pregnancy with the index child compared to 20 and 9% of respective control mothers. More study 1 case mothers experienced unintentional injuries (OR 9.50) and intentional injuries during the index pregnancy (OR 9.33) than the control mothers. Most case mothers began prenatal care in the second trimester. Alcohol use was documented before, during and after each of the three pregnancies. Women of child-bearing age should be screened for alcohol use whenever they present for medical services. Mothers who had a child with FAS decreased their alcohol consumption with the next pregnancy, a finding that supports the importance of prenatal screening throughout pregnancy. Women who receive medical care for injuries should be screened for

  13. A case story, involving the use of maltitol, a sugar alcohol, as a cutting agent in amphetamine and cocaine powders

    DEFF Research Database (Denmark)

    Reitzel, Lotte Ask; Holm, Niels Bjerre; Linnet, Kristian;

    2016-01-01

    In a criminal case involving cutting and resale of amphetamine and cocaine in the Copenhagen area of Denmark, maltitol was used as a cutting agent. The analysis of maltitol in seizures of pure diluents as well as in amphetamine and cocaine powders was carried out using reversed-phase high...... performance liquid chromatography (HPLC) with high-resolution (HR) mass spectrometric detection. Maltitol was identified in four out of nine amphetamine samples and in five out of six cocaine samples from the case in question. The use of maltitol as a cutting agent was considered by the police as a specific...... marker of the particular criminal group under investigation. To support or reject this hypothesis, cocaine and amphetamine samples from a four month period after the involved persons had been arrested were evaluated, also as part of the police investigation. None of these samples contained maltitol...

  14. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Wang, Linlong [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Chen, Liaobin [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause

  15. Prenatal alcohol exposure, adaptive function, and entry into adult roles in a prospective study of young adults.

    Science.gov (United States)

    Lynch, Mary Ellen; Kable, Julie A; Coles, Claire D

    2015-01-01

    Although many studies have demonstrated effects of prenatal alcohol exposure (PAE) on physical, cognitive, and behavioral development in children, few have focused on the long term effects on adults. In this study, data are presented on adaptive function and entry into adult roles in a community sample of young adults with PAE. The expectation was that prenatally exposed adults would show lower adaptive functioning and more difficulty with entry into adult roles than the non-exposed control group and that these effects would be related to the severity of PAE effects. The predominantly African-American, low income sample included adults with a wide range of prenatal exposure (n = 123) as well as control groups for socioeconomic (SES) (n =5 9) and disability (n = 54) status. The mothers of the alcohol-exposed and SES-control group participants were recruited before birth and offspring have been followed up periodically. The disability control group was recruited in adolescence. The adults were interviewed about adaptive function in day-to-day life and adult role entry. Collateral adults who were well-acquainted with each participant were interviewed concerning adaptive function. Results showed that adults who were dysmorphic and/or cognitively affected by PAE had difficulty with adaptive function and entry into adult roles. Males showing cognitive effects with no physical effects were the most severely affected. Results for exposed adults not showing physical or cognitive effects were similar to or more positive than those of the control group for most outcomes. PAE has long-term effects on adaptive outcomes in early adulthood. Additional research should focus on possible interventions at this transition and on factors contributing to the adjustment of the exposed, but unaffected participants. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Mechanisms of Disulfiram-induced Cocaine Abstinence: Antabuse and Cocaine Relapse

    Science.gov (United States)

    Gaval-Cruz, Meriem; Weinshenker, David

    2009-01-01

    The anti-alcoholism drug disulfiram (Antabuse), which is an inhibitor of aldehyde dehydrogenase, induces an aversive reaction to alcohol consumption and thereby helps patients reduce alcohol intake. Recent clinical trials, initiated to investigate whether disulfiram could be used to treat individuals who abuse both alcohol and cocaine, have indicated that disulfiram effectively decreases cocaine consumption. Yet the ability of disulfiram to curb cocaine intake cannot be explained by the disruption of ethanol metabolism. Here, we synthesize clinical and animal data that point to dopamine β-hydroxylase inhibition as a mechanism underlying the efficacy of disulfiram in the treatment of cocaine dependence. PMID:19720750

  17. Demand Curves for Hypothetical Cocaine in Cocaine-Dependent Individuals

    Science.gov (United States)

    Bruner, Natalie R.; Johnson, Matthew W.

    2013-01-01

    Rationale Drug purchasing tasks have been successfully used to examine demand for hypothetical consumption of abused drugs including heroin, nicotine, and alcohol. In these tasks drug users make hypothetical choices whether to buy drugs, and if so, at what quantity, at various potential prices. These tasks allow for behavioral economic assessment of that drug's intensity of demand (preferred level of consumption at extremely low prices) and demand elasticity (sensitivity of consumption to price), among other metrics. However, a purchasing task for cocaine in cocaine-dependent individuals has not been investigated. Objectives This study examined a novel Cocaine Purchasing Task and the relation between resulting demand metrics and self-reported cocaine use data. Methods Participants completed a questionnaire assessing hypothetical purchases of cocaine units at prices ranging from $0.01 to $1,000. Demand curves were generated from responses on the Cocaine Purchasing Task. Correlations compared metrics from the demand curve to measures of real-world cocaine use. Results Group and individual data were well modeled by a demand curve function. The validity of the Cocaine Purchasing Task was supported by a significant correlation between the demand curve metrics of demand intensity and Omax (determined from Cocaine Purchasing Task data) and self-reported measures of cocaine use. Partial correlations revealed that after controlling for demand intensity, demand elasticity and the related measure, Pmax, were significantly correlated with real-world cocaine use. Conclusions Results indicate that the Cocaine Purchasing Task produces orderly demand curve data, and that these data relate to real-world measures of cocaine use. PMID:24217899

  18. Demand curves for hypothetical cocaine in cocaine-dependent individuals.

    Science.gov (United States)

    Bruner, Natalie R; Johnson, Matthew W

    2014-03-01

    Drug purchasing tasks have been successfully used to examine demand for hypothetical consumption of abused drugs including heroin, nicotine, and alcohol. In these tasks, drug users make hypothetical choices whether to buy drugs, and if so, at what quantity, at various potential prices. These tasks allow for behavioral economic assessment of that drug's intensity of demand (preferred level of consumption at extremely low prices) and demand elasticity (sensitivity of consumption to price), among other metrics. However, a purchasing task for cocaine in cocaine-dependent individuals has not been investigated. This study examined a novel Cocaine Purchasing Task and the relation between resulting demand metrics and self-reported cocaine use data. Participants completed a questionnaire assessing hypothetical purchases of cocaine units at prices ranging from $0.01 to $1,000. Demand curves were generated from responses on the Cocaine Purchasing Task. Correlations compared metrics from the demand curve to measures of real-world cocaine use. Group and individual data were well modeled by a demand curve function. The validity of the Cocaine Purchasing Task was supported by a significant correlation between the demand curve metrics of demand intensity and O max (determined from Cocaine Purchasing Task data) and self-reported measures of cocaine use. Partial correlations revealed that after controlling for demand intensity, demand elasticity and the related measure, P max, were significantly correlated with real-world cocaine use. Results indicate that the Cocaine Purchasing Task produces orderly demand curve data, and that these data relate to real-world measures of cocaine use.

  19. Prenatal alcohol exposure increases postnatal acceptability of nicotine odor and taste in adolescent rats.

    Science.gov (United States)

    Mantella, Nicole M; Youngentob, Steven L

    2014-01-01

    Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol's bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine's odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1) or orosensory-mediated responses to nicotine solutions (Experiment 2) were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s) by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are at play, our

  20. Prenatal alcohol exposure increases postnatal acceptability of nicotine odor and taste in adolescent rats.

    Directory of Open Access Journals (Sweden)

    Nicole M Mantella

    Full Text Available Human studies indicate that alcohol exposure during gestation not only increases the chance for later alcohol abuse, but also nicotine dependence. The flavor attributes of both alcohol and nicotine can be important determinants of their initial acceptance and they both share the component chemosensory qualities of an aversive odor, bitter taste and oral irritation. There is a growing body of evidence demonstrating epigenetic chemosensory mechanisms through which fetal alcohol exposure increases adolescent alcohol acceptance, in part, by decreasing the aversion to alcohol's bitter and oral irritation qualities, as well as its odor. Given that alcohol and nicotine have noteworthy chemosensory qualities in common, we investigated whether fetal exposure to alcohol increased the acceptability of nicotine's odor and taste in adolescent rats. Study rats were alcohol-exposed during fetal development via the dams' liquid diet. Control animals received ad lib access to an iso-caloric, iso-nutritive diet throughout gestation. Odorant-induced innate behavioral responses to nicotine odor (Experiment 1 or orosensory-mediated responses to nicotine solutions (Experiment 2 were obtained, using whole-body plethysmography and brief access lick tests, respectively. Compared to controls, rats exposed to fetal alcohol showed an enhanced nicotine odor response that was paralleled by increased oral acceptability of nicotine. Given the common aversive component qualities imbued in the flavor profiles of both drugs, our findings demonstrate that like postnatal alcohol avidity, fetal alcohol exposure also influences nicotine acceptance, at a minimum, by decreasing the aversion of both its smell and taste. Moreover, they highlight potential chemosensory-based mechanism(s by which fetal alcohol exposure increases the later initial risk for nicotine use, thereby contributing to the co-morbid expression with enhanced alcohol avidity. Where common chemosensory mechanisms are

  1. Developmental Trajectories for Visuo-Spatial Attention are Altered by Prenatal Alcohol Exposure: A Longitudinal FMRI Study.

    Science.gov (United States)

    Gautam, P; Nuñez, S C; Narr, K L; Mattson, S N; May, P A; Adnams, C M; Riley, E P; Jones, K L; Kan, E C; Sowell, E R

    2015-12-01

    Functional magnetic resonance imaging (fMRI) reveals brain activation abnormalities during visuo-spatial attention and working memory among those with fetal alcohol spectrum disorders (FASD) in cross-sectional reports, but little is known about how activation changes over time during development within FASD or typically developing children. We studied 30 controls and 31 individuals with FASD over 2 years (7-14 years at first participation) with a total of 122 scans, as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders. Despite comparable performance, there were significant group differences in visuo-spatial activation over time bilaterally in frontal, parietal, and temporal regions. Controls showed an increase in signal intensity in these multiple regions whereas FASD participants showed a decrease in brain activation. Effects were also found in 2 small independent samples from the USA, corroborating the findings from the larger group. Results suggest that the long-lasting effect of prenatal alcohol may impact the maturation of visuo-spatial attention and differentiate those with FASD from controls. Based on this first longitudinal fMRI study in FASD children, our novel findings suggest a possible neural mechanism for attention deficits common among individuals with FASD.

  2. A case story, involving the use of maltitol, a sugar alcohol, as a cutting agent in amphetamine and cocaine powders

    Directory of Open Access Journals (Sweden)

    Reitzel Lotte Ask

    2016-06-01

    Full Text Available In a criminal case involving cutting and resale of amphetamine and cocaine in the Copenhagen area of Denmark, maltitol was used as a cutting agent. The analysis of maltitol in seizures of pure diluents as well as in amphetamine and cocaine powders was carried out using reversed-phase high performance liquid chromatography (HPLC with high-resolution (HR mass spectrometric detection. Maltitol was identified in four out of nine amphetamine samples and in five out of six cocaine samples from the case in question. The use of maltitol as a cutting agent was considered by the police as a specific marker of the particular criminal group under investigation. To support or reject this hypothesis, cocaine and amphetamine samples from a four month period after the involved persons had been arrested were evaluated, also as part of the police investigation. None of these samples contained maltitol. The work described covers the part of the case involving the department of forensic chemistry, and not the whole police investigation, but everything was done within the frames given by the police. To the best of our knowledge, this is the first report of a disaccharide polyol being used as a cutting agent for illicit drugs.

  3. Non-fatal cocaine overdose among injecting and non-injecting cocaine users in Sydney, Australia.

    Science.gov (United States)

    Kaye, Sharlene; Darke, Shane

    2004-10-01

    To investigate the frequency of non-fatal cocaine overdose, and responses to overdoses, among injecting and non-injecting cocaine users. Cross-sectional study. Sydney, Australia. Two hundred current cocaine users. Structured interview. Thirteen per cent of the sample had overdosed on cocaine, 7% in the preceding 12 months. Cocaine injectors were more likely to have overdosed, both ever (17 v 6%) and in the preceding 12 months (9 v 3%). The most common symptoms of overdose were palpitations (68%), intense sweating (44%) and seizures (40%). The use of other drugs in combination with cocaine prior to the most recent overdose was prevalent (64%), most commonly opioids (40%), alcohol (24%) and cannabis (24%). Those who had overdosed were more likely to be female, had longer cocaine use careers, had used more cocaine in the preceding month and preceding 6 months, had higher levels of cocaine dependence and more extensive polydrug use. Twenty-four per cent had witnessed a cocaine overdose, 13% in the preceding 12 months. Injectors were more likely to have witnessed overdoses, both ever (35% v 8%) and in the preceding 12 months (20% v 3%). Experience of, and exposure to, overdose were not rare events. Cocaine users need to be aware of the possibility and nature of overdose, and that cocaine overdose can occur irrespective of method of use. There is a need to emphasise the potential danger of combining cocaine with other drugs.

  4. Prenatal alcohol exposure affects progenitor cell numbers in olfactory bulbs and dentate gyrus of vervet monkeys

    DEFF Research Database (Denmark)

    Burke, Mark W; Inyatkin, Alexey; Ptito, Maurice

    2016-01-01

    cells in the rostral migratory pathway, while production and migration of postnatal neurons into the dentate gyrus may be more complex. The relatively small size of the olfactory bulb, compared to the hippocampus, potentially makes this structure ideal for a rapid analysis. This study used the St. Kitts...... vervet monkey (Chlorocebus sabeus) to (1) investigate the normal developmental sequence of post-natal proliferation in the olfactory bulb and dentate gyrus and (2) determine the effects of naturalistic prenatal ethanol exposure on proliferation at three different ages (neonate, five months and two years......). Using design-based stereology, we found an age-related decrease of actively proliferating cells in the olfactory bulb and dentate gyrus for both control and FAE groups. Furthermore, at the neonatal time point, the FAE group had fewer actively proliferating cells as compared to the control group...

  5. Anticonvulsants for cocaine dependence.

    Science.gov (United States)

    Minozzi, Silvia; Cinquini, Michela; Amato, Laura; Davoli, Marina; Farrell, Michael F; Pani, Pier Paolo; Vecchi, Simona

    2015-04-17

    Cocaine dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Although effective pharmacotherapy is available for alcohol and heroin dependence, none is currently available for cocaine dependence, despite two decades of clinical trials primarily involving antidepressant, anticonvulsivant and dopaminergic medications. Extensive consideration has been given to optimal pharmacological approaches to the treatment of individuals with cocaine dependence, and both dopamine antagonists and agonists have been considered. Anticonvulsants have been candidates for use in the treatment of addiction based on the hypothesis that seizure kindling-like mechanisms contribute to addiction. To evaluate the efficacy and safety of anticonvulsants for individuals with cocaine dependence. We searched the Cochrane Drugs and Alcohol Group Trials Register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6), MEDLINE (1966 to June 2014), EMBASE (1988 to June 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to June 2014), Web of Science (1991 to June 2014) and the reference lists of eligible articles. All randomised controlled trials and controlled clinical trials that focus on the use of anticonvulsant medications to treat individuals with cocaine dependence. We used the standard methodological procedures expected by The Cochrane Collaboration. We included a total of 20 studies with 2068 participants. We studied the anticonvulsant drugs carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate and vigabatrin. All studies compared anticonvulsants versus placebo. Only one study had one arm by which the anticonvulsant was compared with the antidepressant desipramine. Upon comparison of anticonvulsant versus placebo, we found no significant differences for any of the efficacy and safety measures. Dropouts: risk ratio (RR) 0.95, 95

  6. Graphomotor skills in children with prenatal alcohol exposure and fetal alcohol spectrum disorder: A population-based study in remote Australia.

    Science.gov (United States)

    Doney, Robyn; Lucas, Barbara R; Jirikowic, Tracy; Tsang, Tracey W; Watkins, Rochelle E; Sauer, Kay; Howat, Peter; Latimer, Jane; Fitzpatrick, James P; Oscar, June; Carter, Maureen; Elliott, Elizabeth J

    2017-02-01

    Few studies have examined graphomotor skills in children with prenatal alcohol exposure (PAE) or fetal alcohol spectrum disorder (FASD). Graphomotor skills were assessed in 108 predominantly Australian Aboriginal children aged 7.5-9.6 years in remote Western Australia using clinical observations (pencil grasp; writing pressure) and standardised assessment tools (the Evaluation Tool of Children's Handwriting; and the Miller Function and Participation Scales - The Draw-a-Kid Game). Skills were compared between children (i) without PAE, (ii) PAE but not FASD and (iii) FASD. Most children used a transitional pencil grasp and exerted heavy handwriting pressure (83.3% and 30.6% of the cohort). The percentage of letters (M = 62.9%) and words (M = 73.3%) written legibly was low. Children with FASD were more likely than children without PAE to use a cross-thumb grasp (P = 0.027), apply heavy writing pressure (P = 0.036), be unable to write a sentence (P = 0.041) and show poorer word legibility (P = 0.041). There were no significant differences between groups for drawing outcomes, although some children with FASD drew pictures that appeared delayed for their age. There were no significant differences between children without PAE and those with PAE but who were not diagnosed with FASD. Overall, graphomotor skills were poor in this cohort, but children with FASD performed significantly worse than children without PAE. Findings suggest the need for improved occupational therapy services for children in remote regions and evaluation of graphomotor skills in children with PAE. © 2016 Occupational Therapy Australia.

  7. Long-term genomic and epigenomic dysregulation as a consequence of prenatal alcohol exposure: a model for fetal alcohol spectrum disorders

    Directory of Open Access Journals (Sweden)

    Morgan L Kleiber

    2014-06-01

    Full Text Available There is abundant evidence that prenatal alcohol exposure leads to a range of behavioural and cognitive impairments, categorized under the term fetal alcohol spectrum disorders (FASDs. These disorders are pervasive in Western cultures and represent the most common preventable source of neurodevelopmental disabilities. The genetic and epigenetic etiology of these phenotypes, including those factors that may maintain these phenotypes throughout the lifetime of an affected individual, has become a recent topic of investigation. This review integrates recent data that has progressed our understanding FASD as a continuum of molecular events, beginning with cellular stress response and ending with a long-term ‘footprint’ of epigenetic dysregulation across the genome. It reports on data from multiple ethanol-treatment paradigms in mouse models that identify changes in gene expression that occur with respect to neurodevelopmental timing of exposure and ethanol dose. These studies have identified patterns of genomic alteration that are dependent on the biological processes occurring at the time of ethanol exposure. This review also adds to evidence that epigenetic processes such as DNA methylation, histone modifications, and non-coding RNA regulation may underlie long-term changes to gene expression patterns. These may be initiated by ethanol-induced alterations to DNA and histone methylation, particularly in imprinted regions of the genome, affecting transcription which is further fine-tuned by altered microRNA expression. These processes are likely complex, genome-wide, and interrelated. The proposed model suggests a potential for intervention, given that epigenetic changes are malleable and may be altered by postnatal environment. This review accentuates the value of mouse models in deciphering the molecular etiology of FASD, including those processes that may provide a target for the ammelioration of this common yet entirely preventable disorder.

  8. Effects of prenatal alcohol exposure on the development of white matter volume and change in executive function

    Directory of Open Access Journals (Sweden)

    P. Gautam

    2014-01-01

    Full Text Available Prenatal alcohol exposure can cause a wide range of deficits in executive function that persist throughout life, but little is known about how changes in brain structure relate to cognition in affected individuals. In the current study, we predicted that the rate of white matter volumetric development would be atypical in children with fetal alcohol spectrum disorders (FASD when compared to typically developing children, and that the rate of change in cognitive function would relate to differential white matter development between groups. Data were available for 103 subjects [49 with FASD, 54 controls, age range 6–17, mean age = 11.83] with 153 total observations. Groups were age-matched. Participants underwent structural magnetic resonance imaging (MRI and an executive function (EF battery. Using white matter volumes measured bilaterally for frontal and parietal regions and the corpus callosum, change was predicted by modeling the effects of age, intracranial volume, sex, and interactions with exposure status and EF measures. While both groups showed regional increases in white matter volumes and improvement in cognitive performance over time, there were significant effects of exposure status on age-related relationships between white matter increases and EF measures. Specifically, individuals with FASD consistently showed a positive relationship between improved cognitive function and increased white matter volume over time, while no such relationships were seen in controls. These novel results relating improved cognitive function with increased white matter volume in FASD suggest that better cognitive outcomes could be possible for FASD subjects through interventions that enhance white matter plasticity.

  9. Prenatal and childhood growth, and hospitalization for alcohol use disorders in adulthood: the Helsinki birth cohort study.

    Directory of Open Access Journals (Sweden)

    Jari Lahti

    Full Text Available BACKGROUND: Small birth size - an indicator of a sub-optimal prenatal environment - and variation in growth after birth have been associated with non-communicable diseases in later life. We tested whether birth size or growth in childhood associated with the risk of hospital admission for alcohol use disorders (AUDs from early to late adulthood. METHODS: The sample comprised 6544 men and 6050 women born between 1934 and 1944 in Helsinki, Finland. Data on anthropometric measures were extracted from medical records and diagnoses of AUD from the Finnish Hospital Discharge Register and Causes of Death Register covering a 40-year period from 1969 to 2008. RESULTS: Altogether 171 women (2.8% and 657 men (10.0% were diagnosed at a hospital with AUD. After adjusting for major confounders, shorter length at birth, shorter height up to two years of age, and lower weight at two years associated with hospitalization for AUD in women. In men, slower growth in height, particularly from 2 to 7 years, and slower weight gain from 7 to 11 years as well as shorter height and lower weight at 7 and 11 years associated with a diagnosis of AUD in men. CONCLUSIONS: Pre- and postnatal growth associates with the risk for AUD later in life differently in women than in men: the fetal period and infancy seem to be the sensitive periods for women, whereas those for men the occur from toddlerhood onwards.

  10. Reduced attentional scope in cocaine polydrug users.

    Directory of Open Access Journals (Sweden)

    Lorenza S Colzato

    Full Text Available Cocaine is Europe's second preferred recreational drug after cannabis but very little is known about possible cognitive impairments in the upcoming type of recreational cocaine user (monthly consumption. We asked whether recreational use of cocaine impacts early attentional selection processes. Cocaine-free polydrug controls (n = 18 and cocaine polydrug users (n = 18 were matched on sex, age, alcohol consumption, and IQ (using the Raven's progressive matrices, and were tested by using the Global-Local task to measure the scope of attention. Cocaine polydrug users attended significantly more to local aspects of attended events, which fits with the idea that a reduced scope of attention may be associated with the perpetuation of the use of the drug.

  11. Cocaine withdrawal

    Science.gov (United States)

    ... feeling of discomfort Increased appetite Vivid and unpleasant dreams Slowing of activity The craving and depression can ... powerful. Exams and Tests A physical examination and history of cocaine use are often all that is ...

  12. Cocaine intoxication

    Science.gov (United States)

    ... with other substances, which can cause additional symptoms. Exams and Tests Tests may include: Blood chemistries and ... ECG) References Perrone J, Hoffman RS. Cocaine, amphetamines, caffeine, and nicotine. In: Tintinalli JE, Kelen GD, Stapczynski ...

  13. Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats.

    Science.gov (United States)

    Shen, Lang; Liu, Zhongfen; Gong, Jun; Zhang, Li; Wang, Linlong; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2014-01-15

    Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE+ND group, serum corticosterone (CORT) slightly decreased and insulin-like growth factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE+HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE+HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a "two-programming" hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is "the first programming", and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as "the second programming".

  14. Prevalence of DSM-IV and DSM-5 Alcohol, Cocaine, Opioid, and Cannabis Use Disorders in a Largely Substance Dependent Sample

    Science.gov (United States)

    Peer, Kyle; Rennert, Lior; Lynch, Kevin G.; Farrer, Lindsay; Gelernter, Joel; Kranzler, Henry R.

    2012-01-01

    BACKGROUND The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) will soon replace the DSM-IV, which has existed for nearly two decades. The changes in diagnostic criteria have important implications for research and for the clinical care of individuals with Substance Use Disorders (SUDs). METHODS We used the Semi-Structured Assessment for Drug Dependence and Alcoholism to evaluate the lifetime presence of DSM-IV abuse and dependence diagnoses and DSM-5 mild, moderate, or severe SUDs for alcohol, cocaine, opioids, and cannabis in a sample of 7,543 individuals recruited to participate in genetic studies of substance dependence. RESULTS Switches between diagnostic systems consistently resulted in a modestly greater prevalence for DSM-5 SUDs, based largely on the assignment of DSM-5 diagnoses to DSM-IV “diagnostic ophans” (i.e., individuals meeting one or two criteria for dependence and none for abuse, and thus not receiving a DSM-IV SUD diagnosis). The vast majority of these diagnostic switches were attributable to the requirement that only two of 11 criteria be met for a DSM-5 SUD diagnosis. We found evidence to support the omission from DSM-5 of the legal criterion due to its limited diagnostic utility. The addition of craving as a criterion in DSM-5 did not substantially affect the likelihood of an SUD diagnosis. CONCLUSION The greatest advantage of DSM-5 appears to be its ability to capture diagnostic orphans. In this sample, changes reflected in DSM-5 had a minimal impact on the prevalence of SUD diagnoses. PMID:22884164

  15. Prenatal alcohol exposure alters p35, CDK5 and GSK3β in the medial frontal cortex and hippocampus of adolescent mice

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    Samantha L. Goggin

    2014-01-01

    Full Text Available Fetal alcohol spectrum disorders (FASDs are the number one cause of preventable mental retardation. An estimated 2–5% of children are diagnosed as having a FASD. While it is known that children prenatally exposed to alcohol experience cognitive deficits and a higher incidence of psychiatric illness later in life, the pathways underlying these abnormalities remain uncertain. GSK3β and CDK5 are protein kinases that are converging points for a vast number of signaling cascades, including those controlling cellular processes critical to learning and memory. We investigated whether levels of GSK3β and CDK5 are affected by moderate prenatal alcohol exposure (PAE, specifically in the hippocampus and medial frontal cortex of the adolescent mouse. In the present work we utilized immunoblotting techniques to demonstrate that moderate PAE increased hippocampal p35 and β-catenin, and decreased total levels of GSK3β, while increasing GSK3β Ser9 and Tyr216 phosphorylation. Interestingly, different alterations were seen in the medial frontal cortex where p35 and CDK5 were decreased and increased total GSK3β was accompanied by reduced Tyr216 of the enzyme. These results suggest that kinase dysregulation during adolescence might be an important contributing factor to the effects of PAE on hippocampal and medial frontal cortical functioning; and by extension, that global modulation of these kinases may produce differing effects depending on brain region.

  16. Pre-conception and prenatal alcohol exposure from mothers and fathers drinking and head circumference: results from the Norwegian Mother-Child Study (MoBa).

    Science.gov (United States)

    Zuccolo, Luisa; DeRoo, Lisa A; Wills, Andrew K; Davey Smith, George; Suren, Pål; Roth, Christine; Stoltenberg, Camilla; Magnus, Per

    2016-12-23

    Although microcephaly is a feature of Fetal Alcohol Syndrome, it is currently unknown whether low-to-moderate prenatal alcohol exposure affects head circumference. Small magnitude associations reported in observational studies are likely to be misleading due to confounding and misclassification biases. Alternative analytical approaches such as the use of family negative controls (e.g. comparing the effects of maternal and paternal exposure) could help disentangle causal effects. We investigated the association of maternal and paternal alcohol drinking before and early in pregnancy with infant head circumference, using data from 68,244 mother-father-offspring trios from the Norwegian Mother and Child Cohort Study (MoBa) (1999-2009). In analyses adjusted for potential confounders, we found no consistent pattern of association between maternal or paternal alcohol intake before or during pregnancy and offspring head circumference modelled as a continuous outcome. However, we found higher odds of microcephaly at birth for higher paternal, but not maternal, alcohol consumption before pregnancy, and similar but weaker effect estimates for first trimester drinking. Associations with paternal drinking before pregnancy were unexpected and should be regarded as hypothesis generating, until independently replicated, although potentially important given the absence of guidelines on safe drinking levels for men in couples trying for a pregnancy.

  17. Associations of the 5-hydroxytryptamine (Serotonin) Receptor 1B Gene (HTR1B) with Alcohol, Cocaine, and Heroin Abuse

    OpenAIRE

    Cao, Jian; LaRocque, Emily; Li, Dawei

    2013-01-01

    Abnormal serotonergic pathways are implicated in numerous neuropsychiatric disorders including alcohol and drug dependence (abuse). The human 5-hydroxytryptamine (serotonin) receptor 1B, encoded by the HTR1B (5-HT1B) gene, is a presynaptic serotonin autoreceptor that plays an important role in regulating serotonin synthesis and release. Although there was evidence of associations of the HTR1B gene variants in the etiologies of substance use disorders, negative findings were also reported. To ...

  18. Personality traits of cocaine-dependent patients associated with cocaine-positive baseline urine at hospitalization.

    Science.gov (United States)

    de Los Cobos, José Pérez; Siñol, Núria; Bañulus, Enrique; Batlle, Francisca; Tejero, Antoni; Trujols, Joan

    2010-01-01

    Cocaine abstinence at treatment entry is considered a predictor of good response in cocaine dependence treatment. Therefore, identification of factors facilitating pretreatment cocaine abstinence could be useful for developing new therapeutic strategies. This retrospective chart review study examines the association between personality traits and cocaine-positive baseline urinalysis (CPB) in cocaine-dependent inpatients. All 107 participants met DSM-IV criteria for cocaine dependence, and were admitted consecutively to a closed addiction unit for detoxification treatment. Personality was assessed with the Temperament and Character Inventory and the Millon Clinical Multiaxial Inventory (MCMI-II). CPB was detected in 80 patients (74.8%). The logistic regression model solely based on personality dimensions showed that only the MCMI-II avoidant traits were significantly associated with a decreased probability of cocaine-dependent patients presenting CPB. The logistic regression model based on both personality dimensions and substance use-related variables alike retained the number of days of cocaine use during the last 30 days as a risk factor, and alcohol dependence and the MCMI-II schizoid dimension as protective factors in predicting CPB results. Avoidant and schizoid traits are personality dimensions of cocaine-dependent patients that are associated with cocaine abstinence prior to inpatient admission. These findings suggest an inverse relationship between social isolation and CPB. Notwithstanding, more research is needed, not only to assess the generalizability of these findings, but also to enrich the personality and substance use model with variables related to readiness to change.

  19. Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine.

    Science.gov (United States)

    Fitzgerald, Paul J

    2013-10-13

    A wide range of commonly abused drugs have effects on the noradrenergic neurotransmitter system, including alterations during acute intoxication and chronic use of these drugs. It is not established, however, that individual differences in noradrenergic signaling, which may be present prior to use of drugs, predispose certain persons to substance abuse. This paper puts forth the novel hypothesis that elevated noradrenergic signaling, which may be raised largely due to genetics but also due to environmental factors, is an etiological factor in the abuse of a wide range of substances, including alcohol, nicotine, marijuana, heroin, cocaine, and caffeine. Data are reviewed for each of these drugs comprising their interaction with norepinephrine during acute intoxication, long-term use, subsequent withdrawal, and stress-induced relapse. In general, the data suggest that these drugs acutely boost noradrenergic signaling, whereas long-term use also affects this neurotransmitter system, possibly suppressing it. During acute withdrawal after chronic drug use, noradrenergic signaling tends to be elevated, consistent with the observation that norepinephrine lowering drugs such as clonidine reduce withdrawal symptoms. Since psychological stress can promote relapse of drug seeking in susceptible individuals and stress produces elevated norepinephrine release, this suggests that these drugs may be suppressing noradrenergic signaling during chronic use or instead elevating it only in reward circuits of the brain. If elevated noradrenergic signaling is an etiological factor in the abuse of a broad range of substances, then chronic use of pharmacological agents that reduce noradrenergic signaling, such as clonidine, guanfacine, lofexidine, propranolol, or prazosin, may help prevent or treat drug abuse in general.

  20. Mind Over Matter: Cocaine

    Science.gov (United States)

    ... Term(s): Teachers / NIDA Teaching Guide / Mind Over Matter Teaching Guide and Series / Cocaine Print Mind Over Matter: Cocaine Order Free Publication in: English Spanish Download PDF 806.08 KB Cocaine is ...

  1. Effects of sex and housing on social, spatial, and motor behavior in adult rats exposed to moderate levels of alcohol during prenatal development.

    Science.gov (United States)

    Rodriguez, Carlos I; Magcalas, Christy M; Barto, Daniel; Fink, Brandi C; Rice, James P; Bird, Clark W; Davies, Suzy; Pentkowski, Nathan S; Savage, Daniel D; Hamilton, Derek A

    2016-10-15

    Persistent deficits in social behavior, motor behavior, and behavioral flexibility are among the major negative consequences associated with exposure to ethanol during prenatal development. Prior work from our laboratory has linked moderate prenatal alcohol exposure (PAE) in the rat to deficits in these behavioral domains, which depend upon the ventrolateral frontal cortex (Hamilton et al., 2014) [20]. Manipulations of the social environment cause modifications of dendritic morphology and experience-dependent immediate early gene expression in ventrolateral frontal cortex (Hamilton et al., 2010) [19], and may yield positive behavioral outcomes following PAE. In the present study we evaluated the effects of housing PAE rats with non-exposed control rats on adult behavior. Rats of both sexes were either paired with a partner from the same prenatal treatment condition (ethanol or saccharin) or from the opposite condition (mixed housing condition). At four months of age (∼3 months after the housing manipulation commenced), social behavior, tongue protrusion, and behavioral flexibility in the Morris water task were measured as in (Hamilton et al., 2014) [20]. The behavioral effects of moderate PAE were primarily limited to males and were not ameliorated by housing with a non-ethanol exposed partner. Unexpectedly, social behavior, motor behavior, and spatial flexibility were adversely affected in control rats housed with a PAE rat (i.e., in mixed housing), indicating that housing with a PAE rat has broad behavioral consequences beyond the social domain. These observations provide further evidence that moderate PAE negatively affects social behavior, and underscore the importance of considering potential negative effects of housing with PAE animals on the behavior of critical comparison groups.

  2. The Impact of Maternal Cocaine Use on Neonates in Socioeconomic Disadvantaged Population.

    Science.gov (United States)

    Sun, Wei Yue; Chen, William

    1997-01-01

    Reviews literature on prevalence, mechanisms of fetal toxicity, effects of exposure, socioeconomic factors, and social-support programs to increase awareness of the effects of prenatal exposure to cocaine. Emphasizes the need for drug education and social-support programs for disadvantaged pregnant women to prevent and control cocaine use. (EMK)

  3. Prenatal Methamphetamine Exposure Linked with Problems

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    ... of Abuse Alcohol Amphetamines Bath Salts Brain and Addiction Club Drugs Cocaine Emerging Drugs GHB Hallucinogens Heroin Illegal Drugs Inhalants K2/Spice Kratom LSD (Acid) Marijuana MDMA (Ecstasy) Methamphetamine Opioids Other Drugs ...

  4. Cocaine. Specialized Information Service.

    Science.gov (United States)

    Do It Now Foundation, Phoenix, AZ.

    This compilation of journal articles on cocaine includes a report describing cocaine as the recreational drug of the middle class, statistics from the United States Department of Health on health consequences of cocaine use, an article on "speedballing" (use of cocaine and heroin in combination), and a discussion of the various ways…

  5. Comparative behavioral pharmacology and toxicology of cocaine and its ethanol-derived metabolite, cocaine ethyl-ester (cocaethylene)

    Energy Technology Data Exchange (ETDEWEB)

    Katz, J.L.; Terry, P.; Witkin, J.M. (NIDA Addiction Research Center, Baltimore, MD (United States))

    1992-01-01

    The present study compared the behavioral and toxic effects of cocaine and its ethanol derived metabolite, cocaine ethyl-ester (cocaethylene). Both drugs produced qualitatively similar psychomoter stimulant effects. Cocaine and cocaethylene increased locomotor activity in mice, with cocaine approximately four times more potent than cocaethylene. The durations of action of ED{sub 75} doses of each of the drugs were comparable. Each of the drugs also produced stimulation of operant responding in rats. In rats and squirrel monkeys trained to discriminate cocaine injections from saline, cocaine was approximately three to five times more potent than cocaethylene in producing these cocaine-like interoceptive effects. In contrast to the behavioral effects, cocaine and cocaethylene were equipotent in producing convulsions, and cocaethylene was more potent than cocaine in producing lethality. These results suggest that the conversion of cocaine to cocaethylene with simultaneous cocaine and alcohol use may produce an increased risk of toxicity due to a decrease in the potency of cocaethylene in producing psychomotor stimulant effects, and its increased potency in producing toxicity.

  6. Cocaine, Marijuana, Hypertension and Cardiovascular Effects

    Directory of Open Access Journals (Sweden)

    Mohammad Hassan Ghadiani

    2015-07-01

    Full Text Available Cocaine is used by more than 14 million people worldwide, about 0.3 percent of the global population age is 15 to 64 years. After alcohol, cocaine is the most common cause of acute drug-related emergency department visits in the United States. Cocaine consumption is more frequently associated with acute cardiovascular illness.  Cocaine stimulates α1, α2, β1 and β2 adrenergic receptors through increased levels of norepinephrine and a lesser extent epinephrine. The cardiovascular effects of cocaine are thought to be similar and regardless to the route of consumption. An acute coronary syndrome is the most common cardiac problem including myocardial ischemia and infarction even in young persons without atherosclerosis, aortic dissection and rupture, arrhythmias, ventricular tachycardia and fibrillation, asystole and finally sudden death. Other cardiovascular effects that caused by cocaine include coronary artery aneurysm, palpitation, sinus tachycardia, increased systemic vascular resistance and hypertension crisis, left ventricular hypertrophy, myocarditis, cardiomyopathy, myocardial fibrosis, bundle branch block, heart block, supraventricular arrhythmia, accelerated atherosclerosis, hypotension, bradycardia and infective endocarditis  among intravenous users.Cocaine by three mechanisms cause ischemia: 1. increased myocardial oxygen demand, 2. decreased coronary blood flow due to coronary artery vasoconstriction and spasm and 3. Coronary artery thrombosis via activation of platelets, stimulation of platelet aggregation and potentiation of thromboxane production.

  7. Impaired inhibitory control in recreational cocaine users.

    Directory of Open Access Journals (Sweden)

    Lorenza S Colzato

    Full Text Available Chronic use of cocaine is associated with impairment in response inhibition but it is an open question whether and to which degree findings from chronic users generalize to the upcoming type of recreational users. This study compared the ability to inhibit and execute behavioral responses in adult recreational users and in a cocaine-free-matched sample controlled for age, race, gender distribution, level of intelligence, and alcohol consumption. Response inhibition and response execution were measured by a stop-signal paradigm. Results show that users and non users are comparable in terms of response execution but users need significantly more time to inhibit responses to stop-signals than non users. Interestingly, the magnitude of the inhibitory deficit was positively correlated with the individuals lifetime cocaine exposure suggesting that the magnitude of the impairment is proportional to the degree of cocaine consumed.

  8. Alcohol

    Science.gov (United States)

    ... that's how many accidents occur. continue What Is Alcoholism? What can be confusing about alcohol is that ... develop a problem with it. Sometimes, that's called alcoholism (say: al-kuh-HOL - ism) or being an ...

  9. Alcohol

    Science.gov (United States)

    If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...

  10. Chronic inhibition of dopamine β-hydroxylase facilitates behavioral responses to cocaine in mice.

    Directory of Open Access Journals (Sweden)

    Meriem Gaval-Cruz

    Full Text Available The anti-alcoholism medication, disulfiram (Antabuse, decreases cocaine use in humans regardless of concurrent alcohol consumption and facilitates cocaine sensitization in rats, but the functional targets are unknown. Disulfiram inhibits dopamine β-hydroxylase (DBH, the enzyme that converts dopamine (DA to norepinephrine (NE in noradrenergic neurons. The goal of this study was to test the effects of chronic genetic or pharmacological DBH inhibition on behavioral responses to cocaine using DBH knockout (Dbh -/- mice, disulfiram, and the selective DBH inhibitor, nepicastat. Locomotor activity was measured in control (Dbh +/- and Dbh -/- mice during a 5 day regimen of saline+saline, disulfiram+saline, nepicastat+saline, saline+cocaine, disulfiram+cocaine, or nepicastat+cocaine. After a 10 day withdrawal period, all groups were administered cocaine, and locomotor activity and stereotypy were measured. Drug-naïve Dbh -/- mice were hypersensitive to cocaine-induced locomotion and resembled cocaine-sensitized Dbh +/- mice. Chronic disulfiram administration facilitated cocaine-induced locomotion in some mice and induced stereotypy in others during the development of sensitization, while cocaine-induced stereotypy was evident in all nepicastat-treated mice. Cocaine-induced stereotypy was profoundly increased in the disulfiram+cocaine, nepicastat+cocaine, and nepicastat+saline groups upon cocaine challenge after withdrawal in Dbh +/- mice. Disulfiram or nepicastat treatment had no effect on behavioral responses to cocaine in Dbh -/- mice. These results demonstrate that chronic DBH inhibition facilitates behavioral responses to cocaine, although different methods of inhibition (genetic vs. non-selective inhibitor vs. selective inhibitor enhance qualitatively different cocaine-induced behaviors.

  11. Benzylpiperizine-based party pills' impact on the Auckland City Hospital Emergency Department Overdose Database (2002-2004) compared with ecstasy (MDMA or methylene dioxymethamphetamine), gamma hydroxybutyrate (GHB), amphetamines, cocaine, and alcohol.

    Science.gov (United States)

    Theron, Lynn; Jansen, Karl; Miles, Jennifer

    2007-02-16

    To examine the impact of 'party pills' (PP; herbal highs) on the Auckland City Hospital Emergency Department Overdose Database 2002-2004, and to present figures for five other substances in that database. Auckland City Hospital's Emergency Department's overdose database was reviewed for 2002, 2003, and 2004 for 'herbal ingestions' and 'party pills' (PP), ecstasy, methamphetamine, GHB, cocaine, and alcohol. Adverse effects attributed to PP were examined. In 2002, 1 patient presented with PP ingestion; 4 presented in 2003 and 21 in 2004 respectively (poverdose database for 2004. 'Party pills' appeared to have a minor impact on the overdose database at Auckland City Hospital between 2002 and 2004. There was a significant decrease in GHB presentations from 2003 to 2004 (poverdose presentations.

  12. Cocaine exposure impairs multilineage hematopoiesis of human hematopoietic progenitor cells mediated by the sigma-1 receptor [corrected].

    Science.gov (United States)

    Nixon, Christopher C; Schwartz, Brandon H; Dixit, Dhaval; Zack, Jerome A; Vatakis, Dimitrios N

    2015-03-02

    Prenatal exposure to cocaine is a significant source of fetal and neonatal developmental defects. While cocaine associated neurological and cardiac pathologies are well-documented, it is apparent that cocaine use has far more diverse physiological effects. It is known that in some cell types, the sigma-1 receptor mediates many of cocaine's cellular effects. Here we present a novel and concise investigation into the mechanism that underlies cocaine associated hematopoietic pathology. Indeed, this is the first examination of the effects of cocaine on hematopoiesis. We show that cocaine impairs multilineage hematopoiesis from human progenitors from multiple donors and tissue types. We go on to present the first demonstration of the expression of the sigma-1 receptor in human CD34 + human hematopoietic stem/progenitor cells. Furthermore, we demonstrate that these cocaine-induced hematopoietic defects can be reversed through sigma-1 receptor blockade.

  13. Neuroprotective peptide ADNF-9 in fetal brain of C57BL/6 mice exposed prenatally to alcohol

    Directory of Open Access Journals (Sweden)

    Karty Jonathan A

    2011-10-01

    Full Text Available Abstract Background A derived peptide from activity-dependent neurotrophic factor (ADNF-9 has been shown to be neuroprotective in the fetal alcohol exposure model. We investigated the neuroprotective effects of ADNF-9 against alcohol-induced apoptosis using TUNEL staining. We further characterize in this study the proteomic architecture underlying the role of ADNF-9 against ethanol teratogenesis during early fetal brain development using liquid chromatography in conjunction with tandem mass spectrometry (LC-MS/MS. Methods Pregnant C57BL/6 mice were exposed from embryonic days 7-13 (E7-E13 to a 25% ethanol-derived calorie [25% EDC, Alcohol (ALC] diet, a 25% EDC diet simultaneously administered i.p. ADNF-9 (ALC/ADNF-9, or a pair-fed (PF liquid diet. At E13, fetal brains were collected from 5 dams from each group, weighed, and frozen for LC-MS/MS procedure. Other fetal brains were fixed for TUNEL staining. Results Administration of ADNF-9 prevented alcohol-induced reduction in fetal brain weight and alcohol-induced increases in cell death. Moreover, individual fetal brains were analyzed by LC-MS/MS. Statistical differences in the amounts of proteins between the ALC and ALC/ADNF-9 groups resulted in a distinct data-clustering. Significant upregulation of several important proteins involved in brain development were found in the ALC/ADNF-9 group as compared to the ALC group. Conclusion These findings provide information on potential mechanisms underlying the neuroprotective effects of ADNF-9 in the fetal alcohol exposure model.

  14. Meta-analysis of gene expression patterns in animal models of prenatal alcohol exposure suggests role for protein synthesis inhibition and chromatin remodeling

    Science.gov (United States)

    Rogic, Sanja; Wong, Albertina; Pavlidis, Paul

    2017-01-01

    Background Prenatal alcohol exposure (PAE) can result in an array of morphological, behavioural and neurobiological deficits that can range in their severity. Despite extensive research in the field and a significant progress made, especially in understanding the range of possible malformations and neurobehavioral abnormalities, the molecular mechanisms of alcohol responses in development are still not well understood. There have been multiple transcriptomic studies looking at the changes in gene expression after PAE in animal models, however there is a limited apparent consensus among the reported findings. In an effort to address this issue, we performed a comprehensive re-analysis and meta-analysis of all suitable, publically available expression data sets. Methods We assembled ten microarray data sets of gene expression after PAE in mouse and rat models consisting of samples from a total of 63 ethanol-exposed and 80 control animals. We re-analyzed each data set for differential expression and then used the results to perform meta-analyses considering all data sets together or grouping them by time or duration of exposure (pre- and post-natal, acute and chronic, respectively). We performed network and Gene Ontology enrichment analysis to further characterize the identified signatures. Results For each sub-analysis we identified signatures of differential expressed genes that show support from multiple studies. Overall, the changes in gene expression were more extensive after acute ethanol treatment during prenatal development than in other models. Considering the analysis of all the data together, we identified a robust core signature of 104 genes down-regulated after PAE, with no up-regulated genes. Functional analysis reveals over-representation of genes involved in protein synthesis, mRNA splicing and chromatin organization. Conclusions Our meta-analysis shows that existing studies, despite superficial dissimilarity in findings, share features that allow us

  15. Basal regulation of HPA and dopamine systems is altered differentially in males and females by prenatal alcohol exposure and chronic variable stress.

    Science.gov (United States)

    Uban, Kristina A; Comeau, Wendy L; Ellis, Linda A; Galea, Liisa A M; Weinberg, Joanne

    2013-10-01

    Effects of prenatal alcohol exposure (PAE) on central nervous system function include an increased prevalence of mental health problems, including substance use disorders (SUD). The hypothalamic-pituitary-adrenal (HPA) and dopamine (DA) systems have overlapping neurocircuitries and are both implicated in SUD. PAE alters both HPA and dopaminergic activity and regulation, resulting in increased HPA tone and an overall reduction in tonic DA activity. However, effects of PAE on the interaction between HPA and DA systems have not been investigated. The present study examined PAE effects on basal regulation of central stress and DA systems in key brain regions where these systems intersect. Adult Sprague-Dawley male and female offspring from prenatal alcohol-exposed (PAE), pairfed (PF), and ad libitum-fed control (C) groups were subjected to chronic variable stress (CVS) or remained as a no stress (non-CVS) control group. Corticotropin releasing hormone (CRH) mRNA, as well as glucocorticoid and DA receptor (DA-R) expression were measured under basal conditions 24h following the end of CVS. We show, for the first time, that regulation of basal HPA and DA systems, and likely, HPA-DA interactions, are altered differentially in males and females by PAE and CVS. PAE augmented the typical attenuation in weight gain during CVS in males and caused increased weight loss in females. Increased basal corticosterone levels in control, but not PAE, females suggest that PAE alters the profile of basal hormone secretion throughout CVS. CVS downregulated basal CRH mRNA in the prefrontal cortex and throughout the bed nucleus of the stria terminalis (BNST) in PAE females but only in the posterior BNST of control females. PAE males and females exposed to CVS exhibited more widespread upregulation of basal mineralocorticoid receptor mRNA throughout the hippocampus, and an attenuated decrease in DA-R expression throughout the nucleus accumbens and striatum compared to CVS-exposed control

  16. Controlling Cocaine: Supplying Versus Demand Programs

    Science.gov (United States)

    1994-01-01

    programs are administered to preteens , while cocaine use does not normally start until the late teens and early twenties. 7 A primary activity of...initiation for various drugs. Prevention programs attempt to convince preteens to abstain from marijuana, cigarettes, and alcohol. Therefore, to argue that

  17. Prenatal alcohol exposure (PAE) reduces the size of the forepaw representation in forepaw barrel subfield (FBS) cortex in neonatal rats: relationship between periphery and central representation.

    Science.gov (United States)

    Margret, Cecilia P; Chappell, Tyson D; Li, Cheng X; Jan, Taha A; Matta, Shannon G; Elberger, Andrea J; Waters, Robert S

    2006-07-01

    Prenatal alcohol exposure (PAE) alters limb development that may lead to structural and functional abnormalities of the limb reported in children diagnosed with Fetal Alcohol Spectrum Disorder. To determine whether PAE alters the central representation of the forelimb we used the rodent barrel cortex as our model system where it was possible to visualize and quantitatively measure the size of the forepaw representation in the forepaw barrel subfield (FBS) in first somatosensory cortex. In the present study, we examined the effects of PAE on pattern and size of the forepaw and forepaw representation in FBS in neonatal rats at gestational day 32 that corresponds to postnatal day 9. Pregnant Sprague-Dawley rats were chronically intubated with binge doses of ethanol (6 g/kg) from gestational day 1 through gestational day 20. The offspring of the ethanol treated dams comprised the ethanol (EtOH) group. The effect of PAE on the EtOH group was compared with a nutritional-controlled pairfed (PF) group and a normal chowfed (CF) group. The ventral (glabrous) surface area of the forepaw digits, length of digit 2 through digit 5, and the corresponding glabrous forepaw digit representations in the FBS were measured and compared between treatment groups. In rats exposed to in utero alcohol, the sizes of the overall glabrous forepaw and forepaw digits were significantly reduced in EtOH pups compared to CF and PF pups; overall glabrous forepaw area was 11% smaller than CF controls. Glabrous digit lengths were also smaller in EtOH rats compared to CF controls and significantly smaller in digit 2 through digit 4. The glabrous digit representation in FBS was 18% smaller in the EtOH group when compared to the CF treatment. However, PAE did not produce malformations in the forepaw or alter the pattern of the forepaw representation in FBS; instead, PAE significantly reduced both body and brain weights compared to controls. Unexpectedly, little or no correlation was observed between the

  18. Prenatal parenting.

    Science.gov (United States)

    Glover, Vivette; Capron, Lauren

    2017-06-01

    Parenting begins before birth. This includes prenatal maternal and paternal bonding with the baby, and biological effects on fetal development. Recent research has confirmed how prenatal maternal stress can alter the development of the fetus and the child, and that this can persist until early adulthood. Children are affected in different ways depending, in part, on their own genetic makeup. The fetus may also have a direct effect on prenatal maternal mood and later parenting behaviour via the placenta. The father is important prenatally too. An abusive partner can increase the mother's prenatal stress and alter fetal development, but he can also be an important source of emotional support. New research suggests the potential benefits of prenatal interventions, including viewing of prenatal scans and cognitive behavioural therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Cocaine Causes Apoptotic Death in Rat Mesencephalon and Striatum Primary Cultures.

    Science.gov (United States)

    Lepsch, Lucilia B; Planeta, Cleopatra S; Scavone, Critoforo

    2015-01-01

    To study cocaine's toxic effects in vitro, we have used primary mesencephalic and striatal cultures from rat embryonic brain. Treatment with cocaine causes a dramatic increase in DNA fragmentation in both primary cultures. The toxicity induced by cocaine was paralleled with a concomitant decrease in the microtubule associated protein 2 (MAP2) and/or neuronal nucleus protein (NeuN) staining. We also observed in both cultures that the cell death caused by cocaine was induced by an apoptotic mechanism, confirmed by TUNEL assay. Therefore, the present paper shows that cocaine causes apoptotic cell death and inhibition of the neurite prolongation in striatal and mesencephalic cell culture. These data suggest that if similar neuronal damage could be produced in the developing human brain, it could account for the qualitative or quantitative defects in neuronal pathways that cause a major handicap in brain function following prenatal exposure to cocaine.

  20. Prenatal exposure of a girl with autism spectrum disorder to 'horsetail' (Equisetum arvense herbal remedy and alcohol: a case report

    Directory of Open Access Journals (Sweden)

    Martínez-Salcedo Eduardo

    2011-03-01

    Full Text Available Abstract Introduction Autism is a complex neurodevelopmental disorder in which the interactions of genetic, epigenetic and environmental influences are thought to play a causal role. In humans, throughout embryonic and fetal life, brain development is exquisitely susceptible to injury caused by exposure to toxic chemicals present in the environment. Although the use of herbal supplements during pregnancy is relatively common, little information is available on their association with fetal neurodevelopment. This is, to the best of our knowledge, the first report in the literature to associate a new plausible mechanism of neurodevelopmental toxicity with a case of autism spectrum disorder through a vitamin deficiency potentiated by concomitant use of herbal supplements and ethanol exposure. Case presentation We describe the pediatric environmental history of a three-year-old Caucasian girl with an autism spectrum disorder. We utilized her pediatric environmental history to evaluate constitutional, genetic, and environmental factors pertinent to manifestation of neurodevelopment disorders. Both parents reported prenatal exposure to several risk factors of interest. A year prior to conception the mother began a weight loss diet and ingested 1200 mg/day of 'horsetail' (Equisetum arvense herbal remedies containing thiaminase, an enzyme that with long-term use can lead to vitamin deficiency. The mother reported a significant weight loss during the pregnancy and a deficiency of B-complex vitamins. Thiamine (vitamin B1 deficiency could have been potentiated by the horsetail's thiaminase activity and ethanol exposure during pregnancy. No other risk factors were identified. Conclusions A detailed and careful pediatric environmental history, which includes daily intake, herbal remedies and ethanol exposure, should be obtained from all patients with autism spectrum disorder. Maternal consumption of ethanol and of herbal supplements with suspected or

  1. Prevalência da exposição pré-natal à cocaína em uma amostra de recém-nascidos de um hospital geral universitário Prevalence of prenatal exposure to cocaine in a sample of newborns from a university teaching hospital

    Directory of Open Access Journals (Sweden)

    Gabrielle B. da Cunha

    2001-10-01

    Full Text Available OBJETIVO: verificar a prevalência da exposição pré-natal à cocaína em uma amostra de recém-nascidos utilizando dois métodos: a fluorescência polarizada por imunoensaio no mecônio e a entrevista materna. MÉTODO: estudo transversal realizado num hospital geral universitário, abrangendo todos os recém-nascidos nascidos vivos no centro obstétrico do hospital durante o período de 23 de março de 1999 a 1 de junho de 1999 (847 recém-nascidos. A presença de exposição pré-natal à cocaína foi definida por um teste de fluorescência polarizada por imunoensaio positivo para benzoilecgonina no mecônio do RN e/ou por uma entrevista materna positiva. RESULTADOS: a taxa da exposição pré-natal à cocaína foi de 16 casos (2,4%, através da entrevista, e de 25 casos (3,4% através da testagem do mecônio. Foram encontrados 34 casos, com uma prevalência de 4,6%, quando os métodos para a detecção foram considerados de forma complementar. CONCLUSÕES: através deste estudo, foi observado que a testagem meconial é mais eficaz que a entrevista materna no diagnóstico da exposição pré-natal à cocaína. A entrevista aumentou, em relação à testagem do mecônio, em 26% a possibilidade do diagnóstico da exposição; e a testagem do mecônio, em relação à entrevista, aumentou em 53,4% o diagnóstico da exposição.OBJECTIVE: to assess the prevalence of prenatal exposure to cocaine in a sample of newborns using two methods: fluorescence polarization immunoassay and interview with the mother. METHODS: this cross-sectional study was carried out in a university teaching hospital. The population included all live births between March 23, 1999 and June 01, 1999 (n=847. Exposure was determined by a benzoylecgonine-positive meconium specimen and/or by a positive interview with the mother. RESULTS: the prevalence of prenatal exposure to cocaine in this sample was 2.4% (16 cases according to the interviews, and 3.4% (25 cases according to

  2. Anthropometric and Health-Related Behavioral Factors in the Explanation of Social Inequalities in Low Birth Weight in Children with Prenatal Alcohol Exposure

    Directory of Open Access Journals (Sweden)

    Manuela Pfinder

    2014-01-01

    Full Text Available There is evidence for social inequalities in the health status of children with prenatal alcohol exposure (PAE. This study aimed to describe social inequalities in low birth weight (LBW in children/adolescents with PAE and to examine the contribution of anthropometric and health-related behavioral factors to the explanation of social inequalities. A total of 2,159 participants with parental self-reported moderate to regular PAE (enrolled in the cross-sectional German Health Interview and Examination Survey for Children and Adolescents were examined. At similar levels of PAE, the risk of LBW was significantly increased in subjects with a low socioeconomic status (SES (adjusted odds ratio (OR 2.78, 95% confidence interval (CI 1.59, 4.86 and middle SES (adjusted OR 2.04, 95% CI 1.28, 3.24. Maternal height, maternal body mass index (BMI and smoking during pregnancy mediated the association. The mediating effect of maternal height was 12.5% to 33.7%. Maternal BMI explained 7.9% of the socioeconomic difference in LBW between the high and low SES groups in children with PAE. The mediating effect of smoking during pregnancy was 17.3% to 31.5%. Maternal height, maternal BMI and smoking during pregnancy together explained 24.4% to 60.1% of the socioeconomic differences in LBW in children with PAE. A large proportion of the socioeconomic differences in LBW in children with PAE can be attributed to anthropometric and health-related behavioral factors.

  3. Anthropometric and health-related behavioral factors in the explanation of social inequalities in low birth weight in children with prenatal alcohol exposure.

    Science.gov (United States)

    Pfinder, Manuela

    2014-01-08

    There is evidence for social inequalities in the health status of children with prenatal alcohol exposure (PAE). This study aimed to describe social inequalities in low birth weight (LBW) in children/adolescents with PAE and to examine the contribution of anthropometric and health-related behavioral factors to the explanation of social inequalities. A total of 2,159 participants with parental self-reported moderate to regular PAE (enrolled in the cross-sectional German Health Interview and Examination Survey for Children and Adolescents) were examined. At similar levels of PAE, the risk of LBW was significantly increased in subjects with a low socioeconomic status (SES) (adjusted odds ratio (OR) 2.78, 95% confidence interval (CI) 1.59, 4.86) and middle SES (adjusted OR 2.04, 95% CI 1.28, 3.24). Maternal height, maternal body mass index (BMI) and smoking during pregnancy mediated the association. The mediating effect of maternal height was 12.5% to 33.7%. Maternal BMI explained 7.9% of the socioeconomic difference in LBW between the high and low SES groups in children with PAE. The mediating effect of smoking during pregnancy was 17.3% to 31.5%. Maternal height, maternal BMI and smoking during pregnancy together explained 24.4% to 60.1% of the socioeconomic differences in LBW in children with PAE. A large proportion of the socioeconomic differences in LBW in children with PAE can be attributed to anthropometric and health-related behavioral factors.

  4. Alcohol

    NARCIS (Netherlands)

    Hendriks, H.F.; Tol, A. van

    2005-01-01

    Alcohol consumption affects overall mortality. Light to moderate alcohol consumption reduces the risk of coronary heart disease; epidemiological, physiological and genetic data show a causal relationship. Light to moderate drinking is also associated with a reduced risk of other vascular diseases an

  5. Cryptorchidism and maternal alcohol consumption during pregnancy

    DEFF Research Database (Denmark)

    Damgaard, Ida N; Jensen, Tina Kold; Petersen, Jørgen H;

    2007-01-01

    Prenatal exposure to alcohol can adversely affect the fetus. We investigated the association between maternal alcohol consumption during pregnancy and cryptorchidism (undescended testis) among newborn boys.......Prenatal exposure to alcohol can adversely affect the fetus. We investigated the association between maternal alcohol consumption during pregnancy and cryptorchidism (undescended testis) among newborn boys....

  6. Effects of Alcohol on a Fetus

    Science.gov (United States)

    ... ETUS “Of all the substances of abuse (including cocaine, heroin, and marijuana), alcohol produces by far the ... eyes, ears, heart, kidneys, and bones. No single mechanism can account for all the problems that alcohol ...

  7. Gambling Problems Among Community Cocaine Users.

    Science.gov (United States)

    Dufour, Magali; Nguyen, Noël; Bertrand, Karine; Perreault, Michel; Jutras-Aswad, Didier; Morvannou, Adèle; Bruneau, Julie; Berbiche, Djamal; Roy, Élise

    2016-09-01

    Cocaine use is highly prevalent and a major public health problem. While some studies have reported frequent comorbidity problems among cocaine users, few studies have included evaluation of gambling problems. This study aimed to estimate the prevalence of gambling problems and compare those who were at-risk gamblers with non-problem gamblers in terms of mental health problems, substance use problems, and some risk factors (i.e. family antecedents, erroneous perceptions and coping strategies) among individuals who smoke or inject cocaine. A total of 424 smoked or injected cocaine users recruited through community-based programs in Montreal (Quebec) completed the questionnaire, including the Canadian Pathological Gambling Index, the Composite International Diagnostic Interview, the CAGE, and the Severity Dependence Scale. Of the sample, 18.4 % were considered at-risk gamblers, of whom 7.8 % had problems gambling and 10.6 % were moderate-risk gamblers. The at-risk group was more likely to have experienced a recent phobic disorder and alcohol problems than the non-problem group. A multivariate analysis showed that, compared to those who were non-problem gamblers, the at-risk ones were more likely to have lost a large sum of money when they first started gambling, believed that their luck would turn, and gambled in reaction to painful life events. These results indicate the need to include routines for screening to identify gambling problem among cocaine users.

  8. Functional MRI and Response Inhibition in Children Exposed to Cocaine in utero

    Science.gov (United States)

    Sheinkopf, Stephen J.; Lester, Barry M.; Sanes, Jerome N.; Eliassen, James C.; Hutchison, Emmette R.; Seifer, Ronald; LaGasse, Linda L.; Durston, Sarah; Casey, B. J.

    2009-01-01

    This study investigated the potential long-term effects of cocaine exposure on brain functioning using fMRI in school-aged children. The sample included 12 children with prenatal cocaine exposure and 12 non-exposed children (8–9 years old). Groups did not differ on IQ, socioeconomic status, or perinatal risk factors. A response inhibition task was administered during an fMRI scan using a 1.5-T MRI system. Task performance did not differentiate groups, but groups were differentiated by patterns of task-related brain activity. Cocaine-exposed children showed greater activation in the right inferior frontal cortex and caudate during response inhibition, whereas non-exposed children showed greater activations in temporal and occipital regions. These preliminary findings suggest that prenatal cocaine may affect the development of brain systems involved in the regulation of attention and response inhibition. PMID:19372696

  9. Sex differences in psychiatric comorbidity and plasma biomarkers for cocaine addiction in abstinent cocaine-addicted subjects in outpatient settings

    Directory of Open Access Journals (Sweden)

    MARIA ePEDRAZ

    2015-02-01

    Full Text Available There are sex differences in the progression of drug addiction, relapse and response to therapies. Because biological factors participate in these differences, they should be considered when using biomarkers for addiction. In the current study, we evaluated the sex differences in psychiatric comorbidity and the concentrations of plasma mediators that have been reported to be affected by cocaine.Fifty-five abstinent cocaine-addicted subjects diagnosed with lifetime cocaine use disorders (40 men and 15 women and 73 healthy controls (48 men and 25 women were clinically assessed with the diagnostic interview ‘Psychiatric Research Interview for Substance and Mental Disorders’. Plasma concentrations of chemokines, cytokines, N-acyl-ethanolamines and 2-acyl-glycerols were analyzed according to history of cocaine addiction and sex.The results showed that the chemokine concentrations of CCL2/MCP-1 and CXCL12/SDF-1 were only affected by history of cocaine addiction. The plasma concentrations of IL-1β, IL-6, IL-10 and TNFα were higher in control women relative to men, but these concentrations were reduced in cocaine-addicted women. Cytokine concentrations were unaltered in addicted men. Regarding fatty acid derivatives, history of cocaine addiction had a main effect on the concentration of each acyl derivative; whereas N-acyl-ethanolamines were increased overall in the cocaine group, 2-acyl-glycerols were decreased. Interestingly, POEA was only increased in cocaine-addicted women.Regarding psychiatric comorbidity in the cocaine group, women had lower incidence rates of comorbid substance use disorders than did men. For example, alcohol use disorders were found in 80% of men and 40% of women. In contrast, the addicted women had increased prevalences of comorbid psychiatric disorders (mood, anxiety and psychosis disorders.These results demonstrate the existence of a sex influence on plasma biomarkers for cocaine addiction and on the presence of

  10. Prenatal Diagnosis

    Directory of Open Access Journals (Sweden)

    Ozge Ozalp Yuregir

    2012-02-01

    Full Text Available Prenatal diagnosis is the process of determining the health or disease status of the fetus or embryo before birth. The purpose is early detection of diseases and early intervention when required. Prenatal genetic tests comprise of cytogenetic (chromosome assessment and molecular (DNA mutation analysis tests. Prenatal testing enables the early diagnosis of many diseases in risky pregnancies. Furthermore, in the event of a disease, diagnosing prenatally will facilitate the planning of necessary precautions and treatments, both before and after birth. Upon prenatal diagnosis of some diseases, termination of the pregnancy could be possible according to the family's wishes and within the legal frameworks. [Archives Medical Review Journal 2012; 21(1.000: 80-94

  11. Alcohol

    Science.gov (United States)

    ... changes that come from drinking alcohol can make people do stupid or embarrassing things, like throwing up or peeing on themselves. Drinking also gives people bad breath, and no one enjoys a hangover. ...

  12. Treatment of cocaine abuse during pregnancy: translating research to clinical practice.

    Science.gov (United States)

    Hull, Lynn; May, James; Farrell-Moore, Dawn; Svikis, Dace S

    2010-10-01

    In the late-1980s and early-1990s, much attention in America was focused on cocaine abuse. In particular, the effects of prenatal cocaine use on mothers and infants were in the news spotlight. Risks of adverse effects prompted funding for novel treatment programs. More recently, media attention has shifted elsewhere, and specialized treatment resources have grown scarce. This redirection of funding is unfortunate, as social stigma and fear of legal consequences continue to encourage cocaine-abusing pregnant women to hide drug use and avoid prenatal care. The purpose of this article is to summarize the most prominent adverse maternal and fetal/infant effects associated with prenatal cocaine use; review treatment options, focusing on comprehensive care programs of the 1990s as well as recent research on evidence-based practices and their applicability to pregnant women; and highlight the population of prenatal cocaine-abusing women uninterested in treatment, with a focus on promising strategies to promote drug abstinence and other positive health behaviors.

  13. [Cocaine - Characteristics and addiction].

    Science.gov (United States)

    Girczys-Połedniok, Katarzyna; Pudlo, Robert; Jarząb, Magdalena; Szymlak, Agnieszka

    Cocaine use leads to health, social and legal problems. The aim of this paper is to discuss cocaine action, addicts characteristics, use patterns and consequences, as well as addiction treatment methods. A literature review was based on the Medline, PubMed, Polish Medical Bibliography databases and the Silesian Library resources. The Police and Central Statistical Office statistics, as well as the World Health Organization, the European Monitoring Centre for Drugs and Drug Addiction and the National Office for Combating Drug Addiction reports were used. Cocaine leads to mood improvement, appetite decrease, physical and intellectual activity enhancement, euphoria, inflated self-esteem, social networking ease and increased sexual desire. Cocaine hydrochloride is mainly used intranasaly, but also as intravenous and subcutaneous injections. Cocaine use and first addiction treatment fall in later age compared to other psychoactive substances. There is a high men to women ratio among addicts. There is a relationship between cocaine addiction, the presence of other disorders and genetic predisposition to addiction development. Polish reports indicate higher popularity of cocaine among people with a high economic and social status. Although Poland is a country with the low percentage of cocaine use, its popularity is growing. The consequences of cocaine use concern somatic and mental health problems, socioeconomic and legal conditions. The drug plays a role in crimes and traffic accidents. Because of the risks associated with cocaine use, it has been listed in a register of drugs attached to the Act on Counteracting Drug Addiction. Addiction treatment includes psychological, pharmacological and harm reduction strategies. Med Pr 2016;67(4):537-544.

  14. Cocaine Causes Apoptotic Death in Rat Mesencephalon and Striatum Primary Cultures

    Directory of Open Access Journals (Sweden)

    Lucilia B. Lepsch

    2015-01-01

    Full Text Available To study cocaine’s toxic effects in vitro, we have used primary mesencephalic and striatal cultures from rat embryonic brain. Treatment with cocaine causes a dramatic increase in DNA fragmentation in both primary cultures. The toxicity induced by cocaine was paralleled with a concomitant decrease in the microtubule associated protein 2 (MAP2 and/or neuronal nucleus protein (NeuN staining. We also observed in both cultures that the cell death caused by cocaine was induced by an apoptotic mechanism, confirmed by TUNEL assay. Therefore, the present paper shows that cocaine causes apoptotic cell death and inhibition of the neurite prolongation in striatal and mesencephalic cell culture. These data suggest that if similar neuronal damage could be produced in the developing human brain, it could account for the qualitative or quantitative defects in neuronal pathways that cause a major handicap in brain function following prenatal exposure to cocaine.

  15. Cocaine and the nervous system.

    Science.gov (United States)

    Prakash, A; Das, G

    1993-12-01

    Cocaine abuse today has reached greater heights than it did during the first cocaine epidemic in the late nineteenth century. It is estimated that one out of every four Americans has used cocaine and some six million people in the US use it regularly. Although cocaine affects all systems in the body, the central nervous system (CNS) is the primary target. Cocaine blocks the reuptake of neurotransmitters in the neuronal synapses. Almost all CNS effects of cocaine can be attributed to this mechanism. Euphoria, pharmacological pleasure and intense cocaine craving share basis in this system. The effects of cocaine on other organ systems, in addition to its effects on the CNS, account for the majority of the complications associated with cocaine abuse. In this paper, the CNS effects following cocaine administration and their treatment are discussed.

  16. Control Prenatal

    National Research Council Canada - National Science Library

    P. Susana Aguilera, DRA; M.D. Peter Soothill, MR

    2014-01-01

    Los principales objetivos del control prenatal son identificar aquellos pacientes de mayor riesgo, con el fin de realizar intervenciones en forma oportuna que permitan prevenir dichos riesgos y así...

  17. Sex Differences in Psychiatric Comorbidity and Plasma Biomarkers for Cocaine Addiction in Abstinent Cocaine-Addicted Subjects in Outpatient Settings

    Science.gov (United States)

    Pedraz, María; Araos, Pedro; García-Marchena, Nuria; Serrano, Antonia; Romero-Sanchiz, Pablo; Suárez, Juan; Castilla-Ortega, Estela; Mayoral-Cleries, Fermín; Ruiz, Juan Jesús; Pastor, Antoni; Barrios, Vicente; Chowen, Julie A.; Argente, Jesús; Torrens, Marta; de la Torre, Rafael; Rodríguez De Fonseca, Fernando; Pavón, Francisco Javier

    2015-01-01

    effect on POEA and N-arachidonoyl-ethanolamine concentrations. Regarding psychiatric comorbidity in the cocaine group, women had lower incidence rates of comorbid substance use disorders than did men. For example, alcohol use disorders were found in 80% of men and 40% of women. In contrast, the addicted women had increased prevalences of comorbid psychiatric disorders (i.e., mood, anxiety, and psychosis disorders). Additionally, cocaine-addicted subjects showed a relationship between the concentrations of N-stearoyl-ethanolamine and 2-linoleoyl-glycerol and diagnosis of psychiatric comorbidity. These results demonstrate the existence of a sex influence on plasma biomarkers for cocaine addiction and on the presence of comorbid psychopathologies for clinical purposes. PMID:25762940

  18. Fetal Alcohol Exposure

    Science.gov (United States)

    ... her child’s genetic make-up, and changes in gene activity caused by prenatal alcohol exposure. NIH . . . Turning Discovery Into Health ® National Institute on Alcohol Abuse and Alcoholism www. niaaa. nih. gov • 301.443.3860 Interventions ...

  19. Early postpartum pup preference is altered by gestational cocaine treatment: associations with infant cues and oxytocin expression in the MPOA.

    Science.gov (United States)

    Lippard, E T Cox; Jarrett, T M; McMurray, M S; Zeskind, P S; Garber, K A; Zoghby, C R; Glaze, K; Tate, W; Johns, J M

    2015-02-01

    Cross-fostering studies suggest cocaine-induced deficits in maternal behavior could be associated with altered behavior of offspring following prenatal cocaine-exposure. Neonatal vocalizations are an important offspring cue facilitating early interactions between dam and rodent pup offspring and have been shown to be altered following prenatal cocaine-exposure. It is unclear how variations in acoustic parameters of USVs impact maternal behavior and the mechanism(s) underlying these processes. The present study examined differences in cocaine-exposed and control rodent dam maternal preference of cocaine-exposed or untreated pups in a dual choice apparatus. Relationship of preference-like behavior with pup USVs and dam oxytocin expression was explored. Gestational cocaine-exposure interfered with preference-like behavior of dams on postpartum day 1 with cocaine-exposure associated with decreased time spent on the cocaine-exposed pup side compared to the control pup side, and decreases in preference-like behavior associated in part with decreased number of USVs being emitted by cocaine-exposed pups. On postpartum day 5, decreased oxytocin expression in the medial preoptic area was associated with altered preference-like behavior in cocaine-exposed dams, including frequency and latency to touch/sniff pups. Results indicate cocaine's effects on the mother-infant relationship is likely synergistic, in that cocaine influences mother and offspring both independently and concertedly and that variations within pup vocalizations and the oxytocin system may be potential mechanism(s) underlying this synergistic relationship during the postpartum period.

  20. Cocaethylene is more potent than cocaine in mediating lethality.

    Science.gov (United States)

    Hearn, W L; Rose, S; Wagner, J; Ciarleglio, A; Mash, D C

    1991-06-01

    Cocaethylene is a pharmacologically active cocaine metabolite that is formed in the presence of ethanol by the activity of liver enzymes. The pharmacology of cocaethylene has not been extensively investigated and its acute toxicity is unknown. The acute toxicity of cocaethylene was compared to cocaine in Swiss-Webster mice. The LD50 of cocaethylene was 60.7 mg/kg and 63.8 mg/kg in female and male mice, respectively. In comparison, the LD50 of cocaine was 93.0 mg/kg in both female and male mice. These studies demonstrate that the cocaine-alcohol metabolite, cocathylene, is more potent in mediating lethality than the parent drug.

  1. A mechanism for the inhibition of neural progenitor cell proliferation by cocaine.

    Directory of Open Access Journals (Sweden)

    Chun-Ting Lee

    2008-06-01

    Full Text Available BACKGROUND: Prenatal exposure of the developing brain to cocaine causes morphological and behavioral abnormalities. Recent studies indicate that cocaine-induced proliferation inhibition and/or apoptosis in neural progenitor cells may play a pivotal role in causing these abnormalities. To understand the molecular mechanism through which cocaine inhibits cell proliferation in neural progenitors, we sought to identify the molecules that are responsible for mediating the effect of cocaine on cell cycle regulation. METHODS AND FINDINGS: Microarray analysis followed by quantitative real-time reverse transcription PCR was used to screen cocaine-responsive and cell cycle-related genes in a neural progenitor cell line where cocaine exposure caused a robust anti-proliferative effect by interfering with the G1-to-S transition. Cyclin A2, among genes related to the G1-to-S cell cycle transition, was most strongly down-regulated by cocaine. Down-regulation of cyclin A was also found in cocaine-treated human primary neural and A2B5+ progenitor cells, as well as in rat fetal brains exposed to cocaine in utero. Reversing cyclin A down-regulation by gene transfer counteracted the proliferation inhibition caused by cocaine. Further, we found that cocaine-induced accumulation of reactive oxygen species, which involves N-oxidation of cocaine via cytochrome P450, promotes cyclin A down-regulation by causing an endoplasmic reticulum (ER stress response, as indicated by increased phosphorylation of eIF2alpha and expression of ATF4. In the developing rat brain, the P450 inhibitor cimetidine counteracted cocaine-induced inhibition of neural progenitor cell proliferation as well as down-regulation of cyclin A. CONCLUSIONS: Our results demonstrate that down-regulation of cyclin A underlies cocaine-induced proliferation inhibition in neural progenitors. The down-regulation of cyclin A is initiated by N-oxidative metabolism of cocaine and consequent ER stress. Inhibition of

  2. Cocaine and Pregnancy

    Science.gov (United States)

    ... weight. Cocaine may increase the risk for preterm delivery. Babies who are born prematurely often start life with ... Is there any way to know if my baby has been harmed before delivery? If you are worried that your baby may ...

  3. Prenatal Care.

    Science.gov (United States)

    Health Resources and Services Administration (DHHS/PHS), Rockville, MD. Office for Maternal and Child Health Services.

    This booklet is the first in a series of publications designed to provide parents with useful information about childrearing. Contents are organized into three parts. Part I focuses on the pregnancy, prenatal care, development of the baby, pregnant lifestyles, nutrition, common discomforts, and problems of pregnancy. Part II provides information…

  4. Differential effects of the histamine H3 receptor agonist methimepip on dentate granule cell excitability, paired-pulse plasticity and long-term potentiation in prenatal alcohol-exposed rats

    Science.gov (United States)

    Varaschin, Rafael K.; Rosenberg, Martina J.; Hamilton, Derek A.; Savage, Daniel D.

    2016-01-01

    We previously reported that prenatal alcohol-induced deficits in dentate gyrus (DG) long-term potentiation (LTP) are ameliorated by the histamine H3 receptor inverse agonist ABT-239. ABT-239 did not enhance LTP in control rats, suggesting a heightened H3 receptor-mediated inhibition of glutamate release in prenatal alcohol-exposed (PAE) offspring. As the modulation of glutamate release is one important facet of LTP, we examined the effect of methimepip, a histamine H3 receptor agonist, on DG granule cell excitability, glutamate release and LTP in control and PAE rats. Long-Evans rat dams voluntarily consumed either a 0% or 5% ethanol solution four hours daily throughout gestation. Male adult offspring were anesthetized with urethane and electrodes implanted into the entorhinal cortex and DG. PAE reduced coupling of excitatory post-synaptic field potentials to population spikes, an effect mimicked in control rats treated with 1 mg/kg methimepip. Methimepip decreased release probability in controls but not in PAE offspring. GABAergic feedback inhibition of granule cell responsiveness was not affected by either PAE or methimepip. PAE reduced LTP in the DG, another effect mimicked in methimepip-treated control rats. Again, methimepip did not exacerbate the PAE-induced LTP deficit. Thus, while methimepip treatment of control rats mimicked some baseline and activity-dependent deficits observed in saline-treated PAE offspring, methimepip treatment of PAE rats did not exacerbate these deficits. Whether the absence of an added methimepip effect in PAE offspring is a consequence of a “floor effect” for the responses measured or is due to differential drug dose responsiveness will require further investigation. Further, more detailed studies of H3 receptor-mediated responses in vitro may provide clearer insights into the role of the H3 receptor regulation of excitatory transmission at the perforant path - DG synapse in PAE rats. PMID:24818819

  5. [Sigmund Freud and cocaine].

    Science.gov (United States)

    Lebzeltern, G

    1983-11-11

    The basic tenet proposed by J. V. Scheidt states that the narcotic drug, cocaine played a role in the development of psychoanalysis which has been underestimated up to the present day. It is a fact that Freud himself took cocaine (in small doses) for about two years, and that he began his dream interpretation approximately ten years later. Scheidt believes that a long, unconscious conflict related to the cocaine-induced states of euphoria (ten years later) suddenly led to the beginnings of dream interpretation. The question to be answered now is: Why did this happen precisely in 1895? The foundations of psychoanalysis had already been laid, the application of the new method to the treatment of nervous disorders (heart complaints, train phobias, etc.) was certainly obvious. During this self-analysis it became necessary, first of all, to come to terms with the self-reproaches-which lay on the surface and were more accessible to consciousness-related to Freud's cocaine period (Fleischl-Marxow becomes addicted to cocaine, the most terrible night ever experienced, death of this friend, Freud's warning came too late). It was only when Freud has come to terms with this phase of his life that the road to the deepest part, the discovery of the Oedipus complex in the fall of 1897, was cleared.

  6. Cocaine Exposure Is Associated with Subtle Compromises of Infants' and Mothers' Social-Emotional Behavior and Dyadic Features of Their Interaction in the Face-to-Face Still-Face Paradigm

    Science.gov (United States)

    Tronick, E. Z.; Messinger, D. S.; Weinberg, M. K.; Lester, B. M.; LaGasse, L.; Seifer, R.; Bauer, C. R.; Shankaran, S.; Bada, H.; Wright, L. L.; Poole, K.; Liu, J.

    2005-01-01

    Prenatal cocaine and opiate exposure are thought to subtly compromise social and emotional development. The authors observed a large sample of 236 cocaine-exposed and 459 nonexposed infants (49 were opiate exposed and 646 nonexposed) with their mothers in the face-to-face still-face paradigm. Infant and maternal behaviors were microanalytically…

  7. Efficacy of Disulfiram and Cognitive Behavior Therapy in Cocaine-Dependent Outpatients

    Science.gov (United States)

    Carroll, Kathleen M.; Fenton, Lisa R.; Ball, Samuel A.; Nich, Charla; Frankforter, Tami L.; Shi, Julia; Rounsaville, Bruce J.

    2013-01-01

    Context Disulfiram has emerged as a promising treatment for cocaine dependence, but it has not yet been evaluated in general populations of cocaine users. Objectives To compare the effectiveness of disulfiram therapy with that of a placebo condition in reducing cocaine use and to compare the effectiveness of 2 active behavioral therapies—cognitive behavior therapy (CBT) and interpersonal psychotherapy (IPT)—in reducing cocaine use. Design Randomized, placebo-controlled, double-masked (for medication condition), factorial (2×2) trial with 4 treatment conditions: disulfiram plus CBT, disulfiram plus IPT, placebo plus CBT, and placebo plus IPT. Setting A community-based outpatient substance abuse treatment program. Patients A total of 121 individuals meeting the criteria for current cocaine dependence. Interventions Patients received either disulfiram (250 mg/d) or placebo in identical capsules. Medication compliance was monitored using a riboflavin marker procedure. Both behavioral therapies (CBT and IPT) were manual guided and were delivered in individual sessions for 12 weeks. Main Outcome Measures Random regression analyses of self-reported frequency of cocaine use and results of urine toxicology screens. Results Participants assigned to disulfiram reduced their cocaine use significantly more than those assigned to placebo, and those assigned to CBT reduced their cocaine use significantly more than those assigned to IPT (P<.01 for both). Findings were consistent across all study samples (eg, intention to treat, treatment initiators, and treatment completers). Benefits of disulfiram use and CBT were most pronounced for participants who were not alcohol dependent at baseline or who fully abstained from drinking alcohol during treatment. Adverse effects experienced by participants who received disulfiram were mild and were not considerably different from those experienced by participants who received placebo. Conclusions Disulfiram and CBT are effective

  8. Cocaine cardiomyopathy: A case report

    Directory of Open Access Journals (Sweden)

    Georgiev Antonio

    2014-12-01

    Full Text Available Cocaine is the second most common illicit drug used and the most frequent cause of drug related deaths. The use of cocaine is associated with both, acute and chronic complications, that may involve any system, but the most common system affected is cardiovascular one. Cocaine cardiomyopathy may result from the use of cocaine. This article presents a first case in Republic of Macedonia of 24-year-old male with reversible cocaine-related cardiomyopathy. Clinical presentation, laboratory, X-ray, ultrasound findings and treatment are reviewed.

  9. A exposição pré-natal ao álcool como fator de risco para comportamentos disfuncionais: o papel do pediatra Prenatal alcohol exposure as a risk factor for dysfunctional behaviors: the role of the pediatrician

    Directory of Open Access Journals (Sweden)

    Wakana Momino

    2008-08-01

    Full Text Available OBJETIVO: Ainda que as características clássicas da síndrome fetal alcoólica tenham sido descritas desde 1968, a pesquisa sobre a teratogênese do álcool apenas recentemente demonstrou que o cérebro é o órgão do corpo mais vulnerável aos efeitos da exposição pré-natal ao álcool. No presente artigo, fazemos uma revisão da literatura focalizando principalmente os distúrbios comportamentais relacionados à exposição pré-natal ao álcool. FONTES DOS DADOS: Foi realizada uma pesquisa com base no PubMed sobre a literatura publicada entre 1968 e 2006, com as palavras-chave etanol, gestação e comportamento. Foram estabelecidos limites a estudos em humanos. SÍNTESE DOS DADOS: Os dados apresentados nesta revisão sugerem que jovens com efeitos do espectro do álcool fetal estão sob risco maior de terem comportamento social disruptivo, entre outros problemas neurocomportamentais. CONCLUSÕES: Ainda que seja impossível separar completamente a teratogênese sobre o cérebro decorrente da exposição ao álcool de influências ambientais pós-natais como a causa definitiva desses resultados, o pediatra deve ser estimulado ao diagnóstico precoce de crianças afetadas pela síndrome fetal alcoólica e efeitos do espectro do álcool fetal. Isso permite iniciar o manejo e cuidados apropriados para evitar as conseqüências em longo prazo no comportamento e assegurar uma adaptação social e escolar melhor e mais produtiva.OBJECTIVE: Although the classic features of fetal alcohol syndrome have been recognized since 1968, research on alcohol teratogenesis has only recently demonstrated that the brain is the organ in the body most vulnerable to the effects of prenatal alcohol exposure. In this present article, we reviewed the literature focusing mainly on behavioral disturbances related to prenatal ethanol exposure. SOURCES: We performed a PubMed search on the literature published between 1968 and 2006 using the terms ethanol, pregnancy and

  10. 21 CFR 862.3250 - Cocaine and cocaine metabolite test system.

    Science.gov (United States)

    2010-04-01

    ... treatment of cocaine use or overdose. (b) Classification. Class II. ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cocaine and cocaine metabolite test system. 862... Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a) Identification. A cocaine and...

  11. Effects of prenatal substance exposure on infant temperament vary by context.

    Science.gov (United States)

    Locke, Robin L; Lagasse, Linda L; Seifer, Ronald; Lester, Barry M; Shankaran, Seetha; Bada, Henrietta S; Bauer, Charles R

    2016-05-01

    This was a prospective longitudinal multisite study of the effects of prenatal cocaine and/or opiate exposure on temperament in 4-month-olds of the Maternal Lifestyle Study (N = 958: 366 cocaine exposed, 37 opiate exposed, 33 exposed to both drugs, 522 matched comparison). The study evaluated positivity and negativity during The Behavior Assessment of Infant Temperament (Garcia Coll et al., 1988). Parents rated temperament (Infant Behavior Questionnaire; Rothbart, 1981). Cocaine-exposed infants showed less positivity overall, mainly during activity and threshold items, more negativity during sociability items, and less negativity during irritability and threshold items. Latent profile analysis indicated individual temperament patterns were best described by three groups: low/moderate overall reactivity, high social negative reactivity, and high nonsocial negative reactivity. Infants with heavy cocaine exposure were more likely in high social negative reactivity profile, were less negative during threshold items, and required longer soothing intervention. Cocaine- and opiate-exposed infants scored lower on Infant Behavior Questionnaire smiling and laughter and duration of orienting scales. Opiate-exposed infants were rated as less respondent to soothing. By including a multitask measure of temperament we were able to show context-specific behavioral dysregulation in prenatally cocaine-exposed infants. The findings indicate flatter temperament may be specific to nonsocial contexts, whereas social interactions may be more distressing for cocaine-exposed infants.

  12. Prenatal alcohol exposure and autistic spectrum disorders--a population-based prospective study of 80,552 children and their mothers

    DEFF Research Database (Denmark)

    Eliasen, Marie; Tolstrup, Janne S; Nybo Andersen, Anne-Marie;

    2010-01-01

    To examine whether maternal alcohol intake, including binge drinking (intake > or =5 drinks, equivalent to 60 g pure ethanol on a single occasion), is associated with autistic spectrum disorders (ASD) and infantile autism.......To examine whether maternal alcohol intake, including binge drinking (intake > or =5 drinks, equivalent to 60 g pure ethanol on a single occasion), is associated with autistic spectrum disorders (ASD) and infantile autism....

  13. The teratogenicity of cocaine.

    Science.gov (United States)

    Fantel, A G; Macphail, B J

    1982-08-01

    Pregnancy rats and mice received high doses of cocaine hydrochloride by intraperitoneal injection. Despite treatment periods which included most of organogenesis, no increase in congenital abnormalities was observed. Rats showed significant reductions in maternal and fetal weights as well as increased resorption frequencies. Fetal edema was also found. Mice showed only decreased fetal weights with no increase in malformations.

  14. Benzodiazepine inhibits anxiogenic-like response in cocaine or ethanol withdrawn planarians.

    Science.gov (United States)

    Nayak, Sunil; Roberts, Adam; Bires, Kristofer; Tallarida, Christopher S; Kim, Erin; Wu, Michael; Rawls, Scott M

    2016-09-01

    Planarians spend less time in light versus dark environments. We hypothesized that planarians withdrawn from cocaine or ethanol would spend even less time in the light than drug-naive planarians and that a benzodiazepine would inhibit this response. Planarians pretreated in cocaine or ethanol were placed at the midline of a Petri dish containing spring water that was split evenly into dark and light compartments. Planarians withdrawn from cocaine (1, 10, 100 μmol/l) or ethanol (0.01%) spent less time in the light compartment than water controls; however, this withdrawal response to cocaine (100 μmol/l) or ethanol (0.01%) was abolished by clorazepate (0-100 μmol/l). These data suggest that planarians, similar to rodents, show benzodiazepine-sensitive, anxiogenic-like responses during cocaine or alcohol withdrawal.

  15. Emotion recognition during cocaine intoxication.

    Science.gov (United States)

    Kuypers, K P C; Steenbergen, L; Theunissen, E L; Toennes, S W; Ramaekers, J G

    2015-11-01

    Chronic or repeated cocaine use has been linked to impairments in social skills. It is not clear whether cocaine is responsible for this impairment or whether other factors, like polydrug use, distort the observed relation. We aimed to investigate this relation by means of a placebo-controlled experimental study. Additionally, associations between stressor-related activity (cortisol, cardiovascular parameters) induced by the biological stressor cocaine, and potential cocaine effects on emotion recognition were studied. Twenty-four healthy recreational cocaine users participated in this placebo-controlled within-subject study. Participants were tested between 1 and 2 h after treatment with oral cocaine (300 mg) or placebo. Emotion recognition of low and high intensity expressions of basic emotions (fear, anger, disgust, sadness, and happiness) was tested. Findings show that cocaine impaired recognition of negative emotions; this was mediated by the intensity of the presented emotions. When high intensity expressions of Anger and Disgust were shown, performance under influence of cocaine 'normalized' to placebo-like levels while it made identification of Sadness more difficult. The normalization of performance was most notable for participants with the largest cortisol responses in the cocaine condition compared to placebo. It was demonstrated that cocaine impairs recognition of negative emotions, depending on the intensity of emotion expression and cortisol response.

  16. 76 FR 2129 - National Institute on Alcohol Abuse and Alcoholism; Notice of Closed Meeting

    Science.gov (United States)

    2011-01-12

    ... HUMAN SERVICES National Institutes of Health National Institute on Alcohol Abuse and Alcoholism; Notice... personal privacy. Name of Committee: National Institute on Alcohol Abuse and Alcoholism, Special Emphasis Panel, ``Review of the Prenatal Alcohol in Sudden Infant Death Syndrome And Stillbirth (PASS)...

  17. Tips for Teens: The Truth about Cocaine

    Science.gov (United States)

    ... and intense cravings.Cocaine may give users atemporary illusion of power and energy,but it often leaves ... of dollars on cocaine each week. Stay in control. Cocaine impairs your judgment, which may lead to ...

  18. Enhanced Choice for Viewing Cocaine Pictures in Cocaine Addiction

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, S.J.; Goldstein, R.; Moeller, S.J.; Maloney, T. Parvaz, M.A.; Dunning, J.P.; Alia-Klein, N.; Woicik, P.A.; Hajcak, G.; Telang, F.; Wang, G.-J.; Volkow, N.D.; Goldstein, R.Z.

    2009-02-01

    Individuals with cocaine use disorder (CUD) chose cocaine over nondrug rewards. In two newly designed laboratory tasks with pictures, we document this modified choice outside of a cocaine administration paradigm. Choice for viewing cocaine, pleasant, unpleasant, or neutral pictures-under explicit contingencies (choice made between two fully visible side-by-side images) and under more implicit contingencies (selections made between pictures hidden under flipped-over cards)-was examined in 20 CUD and 20 matched healthy control subjects. Subjects also provided self-reported ratings of each picture's pleasantness and arousal. Under both contingencies, CUD subjects chose to view more cocaine pictures than control subjects, group differences that were not fully explained by the self-reported picture ratings. Furthermore, whereas CUD subjects choice for viewing cocaine pictures exceeded choice for viewing unpleasant pictures (but did not exceed choice for viewing pleasant pictures, in contrast to their self-reported ratings), healthy control subjects avoided viewing cocaine pictures as frequently as, or even more than, unpleasant pictures. Finally, CUD subjects with the most cocaine viewing selections, even when directly compared with selections of the pleasant pictures, also reported the most frequent recent cocaine use. Enhanced drug-related choice in cocaine addiction can be demonstrated even for nonpharmacologic (pictorial) stimuli. This choice, which is modulated by alternative stimuli, partly transcends self-reports (possibly indicative of a disconnect in cocaine addiction between self-reports and objective behavior) to provide an objective marker of addiction severity. Neuroimaging studies are needed to establish the neural underpinnings of such enhanced cocaine-related choice.

  19. Alcohol binge drinking during pregnancy and cryptorchidism

    DEFF Research Database (Denmark)

    Strandberg-Larsen, Katrine; Jensen, Morten Søndergaard; Ramlau-Hansen, Cecilia Høst;

    2009-01-01

    Recent studies have suggested gestational weeks 8-14 as a time window of particular importance to the intrauterine development of the male genitalia, and prenatal exposure to alcohol is under suspicion as a risk factor for cryptorchidism. We examined if prenatal exposure to alcohol, and especially...

  20. Novel C-1 Substituted Cocaine Analogs Unlike Cocaine or Benztropine

    OpenAIRE

    Reith, Maarten E. A.; Ali, Solav; Hashim, Audrey; Sheikh, Imran S.; Theddu, Naresh; Gaddiraju, Narendra V.; Mehrotra, Suneet; Schmitt, Kyle C.; Murray, Thomas F.; Sershen, Henry; Unterwald, Ellen M.; Davis, Franklin A.

    2012-01-01

    Despite a wealth of information on cocaine-like compounds, there is no information on cocaine analogs with substitutions at C-1. Here, we report on (R)-(−)-cocaine analogs with various C-1 substituents: methyl (2), ethyl (3), n-propyl (4), n-pentyl (5), and phenyl (6). Analog 2 was equipotent to cocaine as an inhibitor of the dopamine transporter (DAT), whereas 3 and 6 were 3- and 10-fold more potent, respectively. None of the analogs, however, stimulated mouse locomotor activity, in contrast...

  1. Psychiatric morbidity among cocaine and heroin users in the community.

    Science.gov (United States)

    Tortajada, Silvia; Herrero, Ma Jesús; Domingo-Salvany, Antònia; Molist, Gemma; Barrio, Gregorio; de la Fuente, Luís; Brugal, Ma Teresa

    2012-01-01

    Drug abuse is a serious public health problem. Moreover, co-occurring mental health and substance abuse disorders are common among drug users. This paper examines psychiatric disorders of young cocaine and heroin users using the World Mental Health Composite International Diagnostic Interview (WMH-CIDI). A cohort of 1266 young (18-30 years) current regular cocaine (705) and heroin (561) users were recruited outside the health services in Barcelona, Madrid and Seville, Spain. The WMH-CIDI was used to evaluate mental disorders; the Severity of Dependence Scale (SDS) measured the degree of dependence; and the Duke-UNC Functional Social Support Questionnaire (FSSQ) assessed social support, in a crosssectional study design. About 43% was diagnosed with a lifetime mental disorder. The most common diagnoses were depression (37.5%) and specific phobia (6.8%). During the last 12 months, prevalence rates were also slightly higher in heroin group (26.4%) than in cocaine cohort (21.7%). Every day cocaine consumption, having unstable living conditions and low social support were variables highly associated with psychiatric morbidity in cocaine cohort. In heroin cohort, earning money through illegal activities was associated with psychiatric morbidity, while the moderate use of alcohol acted as a protective factor for mental pathology. Morbidity was associated to having received psychiatric/psychological treatment during the last 12 months in both cohorts. This study has shown a relatively high prevalence of psychiatric morbidity in cocaine and heroin users recruited in non-clinical settings. Future studies examining differences between cocaine and heroin patterns of consumption associated with mental diseases are necessary.

  2. Cocaine Self-Administration Produces Long-Lasting Alterations in Dopamine Transporter Responses to Cocaine

    OpenAIRE

    Siciliano, Cody A.; Fordahl, Steve C.; Jones, Sara R.

    2016-01-01

    Cocaine addiction is a debilitating neuropsychiatric disorder characterized by uncontrolled cocaine intake, which is thought to be driven, at least in part, by cocaine-induced deficits in dopamine system function. A decreased ability of cocaine to elevate dopamine levels has been repeatedly observed as a consequence of cocaine use in humans, and preclinical work has highlighted tolerance to cocaine's effects as a primary determinant in the development of aberrant cocaine taking behaviors. Her...

  3. Physiological correlates of neurobehavioral disinhibition that relate to drug use and risky sexual behavior in adolescents with prenatal substance exposure.

    Science.gov (United States)

    Conradt, Elisabeth; Lagasse, Linda L; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles R; Whitaker, Toni M; Hammond, Jane A; Lester, Barry M

    2014-01-01

    Physiological correlates of behavioral and emotional problems, substance use onset and initiation of risky sexual behavior have not been studied in adolescents with prenatal drug exposure. We studied the concordance between baseline respiratory sinus arrhythmia (RSA) at age 3 and baseline cortisol levels at age 11. We hypothesized that children who showed concordance between RSA and cortisol would have lower neurobehavioral disinhibition scores which would in turn predict age of substance use onset and first sexual intercourse. The sample included 860 children aged 16 years participating in the Maternal Lifestyle Study, a multisite longitudinal study of children with prenatal exposure to cocaine and other substances. Structural equation modeling was used to test pathways between prenatal substance exposure, early adversity, baseline RSA, baseline cortisol, neurobehavioral disinhibition, drug use, and sexual behavior outcomes. Concordance was studied by examining separate male and female models in which there were statistically significant interactions between baseline RSA and cortisol. Prenatal substance exposure was operationalized as the number of substances to which the child was exposed. An adversity score was computed based on caregiver postnatal substance use, depression and psychological distress, number of caregiver changes, socioeconomic and poverty status, quality of the home environment, and child history of protective service involvement, abuse and neglect. RSA and cortisol were measured during a baseline period prior to the beginning of a task. Neurobehavioral disinhibition, based on composite scores of behavioral dysregulation and executive dysfunction, substance use and sexual behavior were derived from questionnaires and cognitive tests administered to the child. Findings were sex specific. In females, those with discordance between RSA and cortisol (high RSA and low cortisol or low RSA and high cortisol) had the most executive dysfunction which, in

  4. Trading apples for oranges? Results of an experiment on the effects of Heroin and Cocaine price changes on addicts' polydrug use

    OpenAIRE

    Jofre-Bonet, M.; Petry, N. M.

    2008-01-01

    This paper studies polydrug use patterns in heroin and cocaine addicts. We use data on two experiments to measure the elasticity of several addictive drugs with respect to heroin and cocaine prices. Own and cross price elasticities are estimated while controlling for non-price related sources of variance. The results indicate that heroin addicts have an inelastic demand for heroin, complement heroin consumption with cocaine, marijuana, and alcohol and substitute Valium and cigarettes. Additio...

  5. Pneumorachis after cocaine sniffing

    Directory of Open Access Journals (Sweden)

    S. Challita

    2014-01-01

    Full Text Available Air in the epidural space is called pneumorachis. The usual mechanism of pneumorachis is air diffusion from the mediastinal tissue layers through the inter-vertebral foramen. Alternatively, air can diffuse directly after spine traumas (e.g., blunt deceleration with vertebral dislocation or medical procedures. Several mechanisms could explain pneumomediastinum and pneumorachis after cocaine sniffing. Passive apnea and/or cough that occur after sniffing can cause intra alveolar hyper-pressure, which is responsible for alveolar rupture and air diffusion. Another mechanism is alveolar wall fragility and rupture induced by repeated cocaine sniffing, in turn causing air diffusion to the mediastinum, sub-cutaneous tissues and the epidural space. The diagnosis is usually made on Chest tomography scan. Management consists in close monitoring in the intensive care unit to detect aggravation of pneumomediastinum and pneumorachis, which would require surgical management. Supplemental nasal oxygen can be given to accelerate nitrogen washout. We present a case of a 28 years old male who presented to the emergency department for chest pain directly after sniffing cocaine. A computed tomography scan of the chest showed pneumomediastinum, pneumorachis and sub-cutaneous emphysema. The patient was admitted for 24 h: after that delay, surveillance chest tomodensitometry showed stability, and he could be discharged without further treatment.

  6. Control Prenatal

    Directory of Open Access Journals (Sweden)

    P. Susana Aguilera, DRA.

    2014-11-01

    Full Text Available Los principales objetivos del control prenatal son identificar aquellos pacientes de mayor riesgo, con el fin de realizar intervenciones en forma oportuna que permitan prevenir dichos riesgos y así lograr un buen resultado perinatal. Esto se realiza a través de la historia médica y reproductiva de la mujer, el examen físico, la realización de algunos exámenes de laboratorio y exámenes de ultrasonido. Además es importante promover estilos de vida saludables, la suplementación de ácido fólico, una consejería nutricional y educación al respecto.

  7. Child maltreatment and foster care: unpacking the effects of prenatal and postnatal parental substance use.

    Science.gov (United States)

    Smith, Dana K; Johnson, Amber B; Pears, Katherine C; Fisher, Philip A; DeGarmo, David S

    2007-05-01

    Parental substance use is a well-documented risk for children. However, little is known about specific effects of prenatal and postnatal substance use on child maltreatment and foster care placement transitions. In this study, the authors unpacked unique effects of (a) prenatal and postnatal parental alcohol and drug use and (b) maternal and paternal substance use as predictors of child maltreatment and foster care placement transitions in a sample of 117 maltreated foster care children. Models were tested with structural equation path modeling. Results indicated that prenatal maternal alcohol use predicted child maltreatment and that combined prenatal maternal alcohol and drug use predicted foster care placement transitions. Prenatal maternal alcohol and drug use also predicted postnatal paternal alcohol and drug use, which in turn predicted foster care placement transitions. Findings highlight the potential integrative role that maternal and paternal substance use has on the risk for child maltreatment and foster care placement transitions.

  8. Molecular mechanism for a gateway drug: epigenetic changes initiated by nicotine prime gene expression by cocaine.

    Science.gov (United States)

    Levine, Amir; Huang, Yanyou; Drisaldi, Bettina; Griffin, Edmund A; Pollak, Daniela D; Xu, Shiqin; Yin, Deqi; Schaffran, Christine; Kandel, Denise B; Kandel, Eric R

    2011-11-02

    In human populations, cigarettes and alcohol generally serve as gateway drugs, which people use first before progressing to marijuana, cocaine, or other illicit substances. To understand the biological basis of the gateway sequence of drug use, we developed an animal model in mice and used it to study the effects of nicotine on subsequent responses to cocaine. We found that pretreatment of mice with nicotine increased the response to cocaine, as assessed by addiction-related behaviors and synaptic plasticity in the striatum, a brain region critical for addiction-related reward. Locomotor sensitization was increased by 98%, conditioned place preference was increased by 78%, and cocaine-induced reduction in long-term potentiation (LTP) was enhanced by 24%. The responses to cocaine were altered only when nicotine was administered first, and nicotine and cocaine were then administered concurrently. Reversing the order of drug administration was ineffective; cocaine had no effect on nicotine-induced behaviors and synaptic plasticity. Nicotine primed the response to cocaine by enhancing its ability to induce transcriptional activation of the FosB gene through inhibition of histone deacetylase, which caused global histone acetylation in the striatum. We tested this conclusion further and found that a histone deacetylase inhibitor simulated the actions of nicotine by priming the response to cocaine and enhancing FosB gene expression and LTP depression in the nucleus accumbens. Conversely, in a genetic mouse model characterized by reduced histone acetylation, the effects of cocaine on LTP were diminished. We achieved a similar effect by infusing a low dose of theophylline, an activator of histone deacetylase, into the nucleus accumbens. These results from mice prompted an analysis of epidemiological data, which indicated that most cocaine users initiate cocaine use after the onset of smoking and while actively still smoking, and that initiating cocaine use after smoking

  9. A Proposal for a Prevalence Study of the Use of Alcohol among Women Attending Selected United States Air Force Prenatal Clinics.

    Science.gov (United States)

    1985-06-01

    death C. Major and Minor Malformations I. septal defects 2. labial hypoplasia 3. hemangiomas 4. aberant palmar creases 5. pectus excavatum 6. strabismus...abnormal children (Sokol, 1981). During the 18th century English gin epidemic, members of the Royal College of Physicians noted an increase in fetal wastage...Ulleland in the children of eight alcoholic mothers. This third report finally alerted the modern medical community to the fact that chronic heavy use of

  10. 出生前接触酒精对大鼠小脑中BDNF和TrkB的影响%EFFECTS OF PRENATAL ALCOHOL EXPOSURE ON BDNF - AND TRKB IN THE RAT CERE-BELLAR CORTEX

    Institute of Scientific and Technical Information of China (English)

    金福; 李今子; 池永学; 李红子; 魏宝玉; 苏立明

    2011-01-01

    [Objective] To investigate the changes of BDNF- and TrkB in the rat cerebellar cortex with prenatal alcohol exposure. [Methods] Twenty-four time-pregnant SD rats were divided into three groups on the 6th day of gestation. Alcohol group (n = 6) received 35 calories of liquid alcohol diet every day; Control group (n = 6) was fed a liquid diet in which milk replaced alcohol isocalorically; Surrogate group (n = 12) intook food normally. Blood samples were obtained by cardiac puncture, under anesthesia, from alcohol and control groups within 6 hours after its last pup was born. The plasma concentrations of alcohol and thyroxine were determined at the Department of Clinical Laboratory, and were compared using the Kruskal - Wallis test. Pups of alcohol and control groups were fostered by surrogate mothers and executed at anesthesia at postnatal 0, 7, 14, 21 and 28 days for measuring the distribution and form of BDNF- and TrkB-immunoreactive Purkinje cells via im-munohistochemistry in the cerebellar cortex. [Results] (Dthe blood alcohol concentration was higher in alcohol group dams than in control group, with significant difference (P < 0.05) ; Thyroxine concentration was significantly decrease in alcohol group dams than in control group (P< 0.05). ?A similar developmental pattern of BDNF- and TrkB-immunoreactive Purkinje cell was observed on and after P14 in control pair-fed. These Purkinje cells of alcohol-fed group showed immature features. Single-layer arrangement of these Purkinje cells in alcohol-fed group was not completely achieved throughout postnatal life. In addition, the number of these Purkinje cell decreased at P28 as compared to control pair-fed group. [Conclusion] When dams . Exposure with alcohol within gestation, not only the blood thyroxine concentration was significantly decreased in dams, but also BDNF- and TrkB- synthesis of cerebellar cortex and growth of BDNF- and TrkB- immunoreactive Purkinje cells were impaired in offsprings.%[目的]研究出

  11. Dopaminergic mechanisms of cocaine use

    NARCIS (Netherlands)

    Veeneman - Rijkens, M.M.J.

    2011-01-01

    Cocaine addiction is an enormous medical problem for which there is currently no effective pharmacotherapy. In order to develop treatments for this disorder, it is essential to understand the neurobiological underpinnings of cocaine addiction. One of the behavioral characteristics of addiction is an

  12. Gene x Disease Interaction on Orbitofrontal Gray Matter in Cocaine Addiction

    Energy Technology Data Exchange (ETDEWEB)

    Alia-Klein, N.; Alia-Klein, N.; Parvaz, M.A.; Woicik, P.A.; Konova, A.B.; Maloney, T.; Shumay, E.; Wang, R.; Telang, F.; Biegon, A.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.; Volkow, N.D.; Goldstein, R.Z.

    2011-03-07

    Long-term cocaine use has been associated with structural deficits in brain regions having dopamine-receptive neurons. However, the concomitant use of other drugs and common genetic variability in monoamine regulation present additional structural variability. The objective is to examine variations in gray matter volume (GMV) as a function of lifetime drug use and the genotype of the monoamine oxidase A gene, MAOA, in men with cocaine use disorders (CUD) and healthy male controls. Forty individuals with CUD and 42 controls who underwent magnetic resonance imaging to assess GMV and were genotyped for the MAOA polymorphism (categorized as high- and low-repeat alleles). The impact of cocaine addiction on GMV, tested by (1) comparing the CUD group with controls, (2) testing diagnosis x MAOA interactions, and (3) correlating GMV with lifetime cocaine, alcohol, and cigarette smoking, and testing their unique contribution to GMV beyond other factors. The results are: (1) Individuals with CUD had reductions in GMV in the orbitofrontal, dorsolateral prefrontal, and temporal cortex and the hippocampus compared with controls; (2) The orbitofrontal cortex reductions were uniquely driven by CUD with low- MAOA genotype and by lifetime cocaine use; and (3) The GMV in the dorsolateral prefrontal cortex and hippocampus was driven by lifetime alcohol use beyond the genotype and other pertinent variables. Long-term cocaine users with the low-repeat MAOA allele have enhanced sensitivity to gray matter loss, specifically in the orbitofrontal cortex, indicating that this genotype may exacerbate the deleterious effects of cocaine in the brain. In addition, long-term alcohol use is a major contributor to gray matter loss in the dorsolateral prefrontal cortex and hippocampus, and is likely to further impair executive function and learning in cocaine addiction.

  13. Efficacy of disulfiram and Twelve Step Facilitation in cocaine-dependent individuals maintained on methadone: A randomized placebo-controlled trial

    Science.gov (United States)

    Carroll, Kathleen M.; Nich, Charla; Shi, Julia M.; Eagan, Dorothy; Ball, Samuel A.

    2012-01-01

    Background Cocaine use remains a major problem within methadone maintenance programs. Disulfiram’s efficacy in reducing cocaine use has been demonstrated in several trials, but its relative efficacy among individuals who use versus abstain from alcohol remains unclear Treatment approaches which seek to enhance substance users’ involvement in self-help activities (Twelve Step Facilitation, TSF) have been associated with better outcomes among alcohol and cocaine users, but have rarely been evaluated among methadone-maintained cocaine-opioid users. Methods We conducted a randomized, placebo controlled, double blind (for medication condition), factorial (2×2) trial with 4 treatment conditions: Disulfiram plus TSF, disulfiram plus standard counseling only, placebo plus TSF, and placebo plus standard counseling in the context of a community-based methadone maintenance program. Participants (N=112) received either disulfiram (250 mg/d) or placebo in conjunction with daily methadone maintenance. Results Assignment to TSF was associated with less cocaine use throughout treatment and a higher number of cocaine-negative urines. While there were no significant main effects of disulfiram versus placebo, individuals without an alcohol use disorder demonstrated greater reductions in cocaine use over time when assigned to disulfiram. Conclusions TSF appears feasible in this methadone maintenance program and was associated with modest reductions in cocaine use, an often intractable problem in this setting. Support for the efficacy of disulfiram was weaker, as it appeared effective only for those without a current alcohol use disorder for this sample. PMID:22695473

  14. Snow Control - An RCT protocol for a web-based self-help therapy to reduce cocaine consumption in problematic cocaine users

    Directory of Open Access Journals (Sweden)

    Sullivan Robin

    2011-09-01

    Full Text Available Abstract Background Cocaine use has increased in most European countries, including Switzerland, and many states worldwide. The international literature has described treatment models that target the general population. In addition to supplying informative measures at the level of primary and secondary prevention, the literature also offers web-based self-help tools for problematic substance users, which is in line with tertiary prevention. Such programs, however, have been primarily tested on individuals with problematic alcohol and cannabis consumption, but not on cocaine-dependent individuals. Methods/Design This paper presents the protocol of a randomised clinical trial to test the effectiveness of a web-based self-help therapy to reduce cocaine use in problematic cocaine users. The primary outcome is severity of cocaine dependence. Secondary outcome measures include cocaine craving, consumption of cocaine and other substances of abuse in the past month, and changes in depression characteristics. The therapy group will receive a 6-week self-help therapy to reduce cocaine consumption based on methods of Cognitive Behavioural Therapy, principles of Motivational Interviewing and self-control practices. The control group will be presented weekly psycho-educative information with a quiz. The predictive validity of participant characteristics on treatment retention and outcome will be explored. Discussion To the best of our knowledge, this will be the first randomised clinical trial to test the effectiveness of online self-help therapy to reduce or abstain from cocaine use. It will also investigate predictors of outcome and retention. This trial is registered at Current Controlled Trials and is traceable as NTR-ISRCTN93702927.

  15. Cocaine – Characteristics and addiction

    Directory of Open Access Journals (Sweden)

    Katarzyna Girczys-Połedniok

    2016-08-01

    Full Text Available Cocaine use leads to health, social and legal problems. The aim of this paper is to discuss cocaine action, addicts characteristics, use patterns and consequences, as well as addiction treatment methods. A literature review was based on the Medline, PubMed, Polish Medical Bibliography databases and the Silesian Library resources. The Police and Central Statistical Office statistics, as well as the World Health Organization, the European Monitoring Centre for Drugs and Drug Addiction and the National Office for Combating Drug Addiction reports were used. Cocaine leads to mood improvement, appetite decrease, physical and intellectual activity enhancement, euphoria, inflated self-esteem, social networking ease and increased sexual desire. Cocaine hydrochloride is mainly used intranasaly, but also as intravenous and subcutaneous injections. Cocaine use and first addiction treatment fall in later age compared to other psychoactive substances. There is a high men to women ratio among addicts. There is a relationship between cocaine addiction, the presence of other disorders and genetic predisposition to addiction development. Polish reports indicate higher popularity of cocaine among people with a high economic and social status. Although Poland is a country with the low percentage of cocaine use, its popularity is growing. The consequences of cocaine use concern somatic and mental health problems, socioeconomic and legal conditions. The drug plays a role in crimes and traffic accidents. Because of the risks associated with cocaine use, it has been listed in a register of drugs attached to the Act on Counteracting Drug Addiction. Addiction treatment includes psychological, pharmacological and harm reduction strategies. Med Pr 2016;67(4:537–544

  16. COCAINE CARDIOMYOPATHY—A CASE REPORT

    OpenAIRE

    Georgiev Antonio; Zhivadinovik Julija

    2014-01-01

    Abstract: Cocaine is the second most common illicit drug used and the most frequent cause of drug related deaths. The use of cocaine is associated with both, acute and chronic complications, that may involve any system, but the most common system affected is cardiovascular one. Cocaine cardiomyopathy may result from the use of cocaine. This article presents a first case in Republic of Macedonia of 24-year-old male with reversible cocaine- related cardiomyopathy. Clinical presentation...

  17. Retinal hemorrhages associated with in utero exposure to cocaine. Experimental and clinical findings.

    Science.gov (United States)

    Silva-Araújo, A; Tavares, M A; Patacao, M H; Carolino, R M

    1996-01-01

    The use of drugs of abuse--e.g., cocaine--during pregnancy has been associated with abnormalities of the visual system. The authors studied the effects of prenatal exposure to drugs of abuse, especially cocaine, on the vascular system of the retina in newborn infants and in an experimental model in the rat. The animal study was conducted in pregnant Wistar rats injected subcutaneously with cocaine hydrochloride (60 mg/kg body weight/day) from gestation days 8 to 22. Male offspring were killed at postnatal days 7, 14, and 30 and perfused with fixative, and the retinas were dissected and processed for microscopic observation. The ophthalmologic observations were conducted in a population of newborn infants born to women who abused many drugs during pregnancy and in a control group of women with no history of illicit drug use. Vascular disruptive lesions were seen after prenatal exposure to cocaine in the rat: round intraretinal hemorrhages, ischemic and hypoperfused areas located at the temporal part and often extending from the posterior pole to the periphery of the retina. The ophthalmologic observation of the newborns showed a higher incidence of vascular disruptive lesions in infants in whom exposure to drugs of abuse was affirmative during pregnancy. In the cases in which cocaine consumption was reported, they consisted in blot full-thickness hemorrhages with rounded domed contours suggestive of venous occlusion and retinal ischemia, very similar to the lesions seen in the animal model. These hemorrhagic lesions, morphologically similar to neonatal retinal hemorrhages, had a higher incidence than in controls; they also took longer to resolve when compared with the reabsorption time of the neonatal hemorrhages due to birth trauma and the hemorrhagic lesions in newborns of mothers in whom consumption of other drugs--but not cocaine--were reported. A topographic and morphologic parallelism can be established between the retinal vascular alterations found in humans

  18. Later Prenatal Checkups

    Science.gov (United States)

    ... report card Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ... Last reviewed: May, 2011 Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ...

  19. Prenatal Care Checkup

    Science.gov (United States)

    ... report card Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ... Careers Archives Health Topics Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ...

  20. Prenatal ultrasound - slideshow

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/presentations/100197.htm Prenatal ultrasound - series—Procedure, part 1 To use the sharing ... Editorial team. Related MedlinePlus Health Topics Prenatal Testing Ultrasound A.D.A.M., Inc. is accredited by ...

  1. Cocaine tolerance in honey bees.

    Directory of Open Access Journals (Sweden)

    Eirik Søvik

    Full Text Available Increasingly invertebrates are being used to investigate the molecular and cellular effects of drugs of abuse to explore basic mechanisms of addiction. However, in mammals the principle factors contributing to addiction are long-term adaptive responses to repeated drug use. Here we examined whether adaptive responses to cocaine are also seen in invertebrates using the honey bee model system. Repeated topical treatment with a low dose of cocaine rendered bees resistant to the deleterious motor effects of a higher cocaine dose, indicating the development of physiological tolerance to cocaine in bees. Cocaine inhibits biogenic amine reuptake transporters, but neither acute nor repeated cocaine treatments caused measurable changes in levels of biogenic amines measured in whole bee brains. Our data show clear short and long-term behavioural responses of bees to cocaine administration, but caution that, despite the small size of the bee brain, measures of biogenic amines conducted at the whole-brain level may not reveal neurochemical effects of the drug.

  2. Structure-affinity relationship of the cocaine-binding aptamer with quinine derivatives.

    Science.gov (United States)

    Slavkovic, Sladjana; Altunisik, Merve; Reinstein, Oren; Johnson, Philip E

    2015-05-15

    In addition to binding its target molecule, cocaine, the cocaine-binding aptamer tightly binds the alkaloid quinine. In order to understand better how the cocaine-binding aptamer interacts with quinine we have used isothermal titration calorimetry-based binding experiments to study the interaction of the cocaine-binding aptamer to a series of structural analogs of quinine. As a basis for comparison we also investigated the binding of the cocaine-binding aptamer to a set of cocaine metabolites. The bicyclic aromatic ring on quinine is essential for tight affinity by the cocaine-binding aptamer with 6-methoxyquinoline alone being sufficient for tight binding while the aliphatic portion of quinine, quinuclidine, does not show detectable binding. Compounds with three fused aromatic rings are not bound by the aptamer. Having a methoxy group at the 6-position of the bicyclic ring is important for binding as substituting it with a hydrogen, an alcohol or an amino group all result in lower binding affinity. For all ligands that bind, association is driven by a negative enthalpy compensated by unfavorable binding entropy.

  3. Sex differences in self-reported and physiological response to oral cocaine and placebo in humans.

    Science.gov (United States)

    Singha, A K; McCance-Katz, E F; Petrakis, I; Kosten, T R; Oliveto, A

    2000-11-01

    Self-report and physiological data from 27 male and 8 female cocaine-abusing volunteers exposed to cocaine (80 mg/70 kg p.o.) and placebo were examined for sex differences in their responses. Females reported significantly greater baseline ratings on the Pentobarbital-Chlorpromazine-Alcohol Group (PCAG) (sedation) and Lysergic Acid Diethylamide (LSD) (dysphoria) subscales of the Addiction Research Center Inventory-Short Form (ARCI) relative to males. In addition, females reported significantly greater ratings on the Visual Analogs Scales (VAS) Bad Drug Effects and Anxious/Nervous scales relative to males, regardless of drug. Cocaine produced greater increase in systolic blood pressure in males following cocaine, whereas females showed greater increases following placebo. These results suggest that a placebo control is necessary to determine sex differences in response to an active drug.

  4. Alcoholism and Alcohol Abuse

    Science.gov (United States)

    ... their drinking causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or alcohol dependence, is a disease that causes ... groups. NIH: National Institute on Alcohol Abuse and Alcoholism

  5. Cocaine use among American adolescents and young adults.

    Science.gov (United States)

    O'Malley, P M; Johnston, L D; Bachman, J G

    1985-01-01

    In this chapter, we have tried to provide some objective information about the levels of and recent trends in cocaine use among America's adolescents and young adults, as well as some of their attitudes and beliefs about the drug and their reasons for using it. We have also examined cross-time patterns of use, certain predictors of use, and some of the conditions of the social and physical environments which are associated with use. Overall, we have found levels of use to be relatively stable for the past several years after a period of rapid increase between 1976 and 1979. We also found a strong age effect, with cocaine use increasing in the first few years after high school. The levels of use, though stable recently, are disturbingly high, particularly among young adults in their early to mid twenties. Self reported use has followed patterns that parallel exposure to use and use by friend, as would be expected, assuming valid measures. Perceived availability also has moved in tandem with these other measures. The great majority of today's seniors believe regular use to be dangerous, and 77% disapprove of even experimenting with cocaine. Use is found most frequently in the western and northeastern regions of the country, in more urban areas, among males, and among those who are not college-bound. Neither socioeconomic status nor personal income are very strongly associated with use; but a history of truancy, going out frequently in the evenings, and having relatively low religious involvement are. Cocaine users tend to use other illicit drugs (particularly marijuana) and to be cigarette smokers and heavy drinkers much more frequently than nonusers. Thus, there is little evidence that cocaine involves a separate drug-using syndrome. In fact, it is not uncommon for cocaine users to use marijuana or alcohol concurrently. When taking cocaine, high school students most often snort it, though some (24% of recent users) smoke it while only 4% of the users inject it. It

  6. Cocaine depresses GABAA current of hippocampal neurons.

    Science.gov (United States)

    Ye, J H; Liu, P L; Wu, W H; McArdle, J J

    1997-10-01

    Although blockade of dopamine re-uptake and the resulting elevation of excitatory agonists is commonly thought the primary mechanism of cocaine-induced seizures, it is possible that other neurotransmitters such as gamma-aminobutyric acid (GABA) are involved. To examine this possibility, the effects of cocaine on the whole cell GABA current (IGABA) of freshly isolated rat hippocampal neurons were investigated with the patch-clamp technique. Preincubation or acute application of cocaine reversibly suppressed IGABA. The IC50 was 127 microM when cocaine was applied before the application of GABA. The concentration-response relations of cocaine in various GABA concentrations revealed that cocaine inhibited IGABA non-competitively. This effect of cocaine appeared to be independent of voltage. The present study suggests that the GABA receptor/channel complex is also a target for cocaine's action. The suppression of IGABA may contribute to cocaine-induced seizures.

  7. Disulfiram Attenuates Drug-Primed Reinstatement of Cocaine Seeking via Inhibition of Dopamine β-Hydroxylase

    Science.gov (United States)

    Schroeder, Jason P; Cooper, Debra A; Schank, Jesse R; Lyle, Megan A; Gaval-Cruz, Meriem; Ogbonmwan, Yvonne E; Pozdeyev, Nikita; Freeman, Kimberly G; Iuvone, P Michael; Edwards, Gaylen L; Holmes, Philip V; Weinshenker, David

    2010-01-01

    The antialcoholism medication disulfiram (Antabuse) inhibits aldehyde dehydrogenase (ALDH), which results in the accumulation of acetaldehyde upon ethanol ingestion and produces the aversive ‘Antabuse reaction' that deters alcohol consumption. Disulfiram has also been shown to deter cocaine use, even in the absence of an interaction with alcohol, indicating the existence of an ALDH-independent therapeutic mechanism. We hypothesized that disulfiram's inhibition of dopamine β-hydroxylase (DBH), the catecholamine biosynthetic enzyme that converts dopamine (DA) to norepinephrine (NE) in noradrenergic neurons, underlies the drug's ability to treat cocaine dependence. We tested the effects of disulfiram on cocaine and food self-administration behavior and drug-primed reinstatement of cocaine seeking in rats. We then compared the effects of disulfiram with those of the selective DBH inhibitor, nepicastat. Disulfiram, at a dose (100 mg/kg, i.p.) that reduced brain NE by ∼40%, did not alter the response for food or cocaine on a fixed ratio 1 schedule, whereas it completely blocked cocaine-primed (10 mg/kg, i.p.) reinstatement of drug seeking following extinction. A lower dose of disulfiram (10 mg/kg) that did not reduce NE had no effect on cocaine-primed reinstatement. Nepicastat recapitulated the behavioral effects of disulfiram (100 mg/kg) at a dose (50 mg/kg, i.p.) that produced a similar reduction in brain NE. Food-primed reinstatement of food seeking was not impaired by DBH inhibition. Our results suggest that disulfiram's efficacy in the treatment of cocaine addiction is associated with the inhibition of DBH and interference with the ability of environmental stimuli to trigger relapse. PMID:20736996

  8. Infant Neurobehavioral Dysregulation Related to Behavior Problems in Children with Prenatal Substance Exposure

    Science.gov (United States)

    Lester, Barry M.; Bagner, Daniel M.; Liu, Jing; LaGasse, Linda L.; Seifer, Ronald; Bauer, Charles R.; Shankaran, Seetha; Bada, Henrietta; Higgins, Rosemary D.; Das, Abhik

    2010-01-01

    OBJECTIVE To test a developmental model of neurobehavioral dysregulation relating prenatal substance exposure to behavior problems at age 7. PATIENTS AND METHODS The sample included 360 cocaine-exposed and 480 unexposed children from lower to lower middle class families of which 78% were African American. Structural equation modeling (SEM) was used to test models whereby prenatal exposure to cocaine and other substances would result in neurobehavioral dysregulation in infancy, which would predict externalizing and internalizing behavior problems in early childhood. SEM models were developed for individual and combined parent and teacher report for externalizing, internalizing, and total problem scores on the Child Behavior Checklist. RESULTS The Goodness of Fit Statistics indicated that all of the models met criteria for adequate fit with 7 of the 9 models explaining 18 to 60% of the variance in behavior problems at age 7. The paths in the models indicate that there are direct effects of prenatal substance exposure on 7-year behavior problems as well as indirect effects, including neurobehavioral dysregulation. CONCLUSIONS Prenatal substance exposure affects behavior problems at age 7 through two mechanisms. The direct pathway is consistent with a teratogenic effect. Indirect pathways suggest cascading effects where prenatal substance exposure results in neurobehavioral dysregulation manifesting as deviations in later behavioral expression. Developmental models provide an understanding of pathways that describe how prenatal substance exposure affects child outcome and have significant implications for early identification and prevention. PMID:19822596

  9. A double-blind, placebo-controlled pilot trial of acamprosate for the treatment of cocaine dependence.

    Science.gov (United States)

    Kampman, Kyle M; Dackis, Charles; Pettinati, Helen M; Lynch, Kevin G; Sparkman, Thorne; O'Brien, Charles P

    2011-03-01

    Acamprosate is a medication shown to be effective for the treatment of alcohol dependence. Although the exact mechanism of action of acamprosate is unknown, evidence suggests that it decreases excitatory amino acid activity by post-synaptic inhibition of the NMDA subtype of glutamate receptors. It is possible that the activity of acamprosate via modulating glutamatergic activity could also reduce craving for cocaine and impact abstinence in cocaine dependence. Therefore, we conducted a double-blind placebo-controlled pilot trial of acamprosate for the treatment of cocaine dependence. Sixty male and female cocaine dependent patients were included in a nine week double-blind, placebo-controlled trial. After a one-week baseline, patients were randomized to receive acamprosate 666 mg three times daily or identical placebo tablets for eight weeks. The primary outcome measure was cocaine use as determined by twice weekly urine drug screens. Thirty-six patients (60%) completed the trial, with no significant between-group difference in treatment retention. Percent cocaine positive urine drug screens did not differ between the two groups. Acamprosate was no better than placebo in reducing cocaine craving, reducing cocaine withdrawal symptoms, or improving measures of drug use severity from the Addiction Severity Index. Adverse events in this trial were generally mild and were evenly distributed between the two groups. Acamprosate was well tolerated but was no more efficacious than placebo in promoting abstinence from cocaine in cocaine dependent patients. Acamprosate does not appear to be a promising medication for the treatment of cocaine dependence. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Treatment of cocaine craving with as-needed nalmefene, a partial κ opioid receptor agonist: first clinical experience.

    Science.gov (United States)

    Grosshans, Martin; Mutschler, Jochen; Kiefer, Falk

    2015-07-01

    The treatment of cocaine dependence is difficult as no approved pharmacotherapy is available as yet. However, in preclinical and clinical trials, a variety of compounds were tested for suitability as inhibitors of craving for and relapse into the use of cocaine, among these antidepressants, antiepileptics, dopamine agonists, disulfiram, and naltrexone. Nalmefene, a structural derivative of naltrexone, shares with its parent compound approval (granted by the European Medical Agency in 2013) as a medication for the treatment of alcohol addiction in the European Union. It differs from naltrexone by a higher affinity for the δ opioid-receptors and a partial agonistic affinity to the κ opioid-receptors. It should be noted that patients addicted to cocaine show a considerable increase in κ receptors in the nucleus accumbens. This report describes the case of an abstinent cocaine-addicted patient regularly afflicted with cravings for cocaine. The patient took as-needed nalmefene for 5 months whenever she developed a craving for cocaine. For most of these interventions, the patient reported an abatement of craving and could avoid relapsing into cocaine consumption. This effect may be accounted for by nalmefene acting, other than naltrexone, as a partial agonist of the κ opioid-receptors. Therefore, nalmefene might be a promising new option in the pharmacological repertoire for the treatment of cocaine addiction.

  11. Diagnóstico Prenatal

    OpenAIRE

    2010-01-01

    Diagnóstico Prenatal/ propósitos del diagnóstico prenatal/ Tamizaje a partir del Control Prenatal/ Pacientes de bajo riesgo/ Tamizaje bioquímico/ Pacientes de alto riesgo/ Pruebas invasivas y no invasivas

  12. Cocaine- and amphetamine-regulated transcript (CART signaling within the paraventricular thalamus modulates cocaine-seeking behaviour.

    Directory of Open Access Journals (Sweden)

    Morgan H James

    Full Text Available BACKGROUND: Cocaine- and amphetamine-regulated transcript (CART has been demonstrated to play a role in regulating the rewarding and reinforcing effects of various drugs of abuse. A recent study demonstrated that i.c.v. administration of CART negatively modulates reinstatement of alcohol seeking, however, the site(s of action remains unclear. We investigated the paraventricular thalamus (PVT as a potential site of relapse-relevant CART signaling, as this region is known to receive dense innervation from CART-containing hypothalamic cells and to project to a number of regions known to be involved in mediating reinstatement, including the nucleus accumbens (NAC, medial prefrontal cortex (mPFC and basolateral amygdala (BLA. METHODOLOGY/PRINCIPAL FINDINGS: Male rats were trained to self-administer cocaine before being extinguished to a set criterion. One day following extinction, animals received intra-PVT infusions of saline, tetrodotoxin (TTX; 2.5 ng, CART (0.625 µg or 2.5 µg or no injection, followed by a cocaine prime (10 mg/kg, i.p.. Animals were then tested under extinction conditions for one hour. Treatment with either TTX or CART resulted in a significant attenuation of drug-seeking behaviour following cocaine-prime, with the 2.5 µg dose of CART having the greatest effect. This effect was specific to the PVT region, as misplaced injections of both TTX and CART resulted in responding that was identical to controls. CONCLUSIONS/SIGNIFICANCE: We show for the first time that CART signaling within the PVT acts to inhibit drug-primed reinstatement of cocaine seeking behaviour, presumably by negatively modulating PVT efferents that are important for drug seeking, including the NAC, mPFC and BLA. In this way, we identify a possible target for future pharmacological interventions designed to suppress drug seeking.

  13. Cocaine and "pharmacological kindling" in the rat.

    Science.gov (United States)

    Stripling, J S

    1983-11-01

    The concept of "pharmacological kindling" has been used to explain the behavioral sensitization to cocaine produced by repeated administration of subconvulsive doses. This idea was tested by the repeated administration of cocaine to rats followed by electrical kindling of the olfactory bulb (a site at which cocaine has prominent electrophysiologic effects). No significant effect of cocaine on kindling was found. The relationship of this finding to studies using other drugs is discussed.

  14. Citalopram enhances cocaine's subjective effects in rats

    OpenAIRE

    Soto, Paul L.; Hiranita, Takato; Katz, Jonathan L.

    2009-01-01

    Serotonin-selective reuptake inhibitors (SSRIs) have been shown to enhance the locomotor stimulatory, discriminative-stimulus, and convulsive effects of cocaine in rodents. A pharmacokinetic mechanism for the interaction is supported by increases in the brain levels of cocaine by fluoxetine treatment. Furthermore, the locomotor-stimulant effects of cocaine in rodents are enhanced by fluoxetine and fluvoxamine, SSRIs known to inhibit cocaine-metabolizing cytochrome P450 enzymes, whereas citalo...

  15. Reduced attentional scope in cocaine polydrug users

    NARCIS (Netherlands)

    Colzato, L.S.; van den Wildenberg, W.P.M.; Hommel, B.

    2009-01-01

    Cocaine is Europe's second preferred recreational drug after cannabis but very little is known about possible cognitive impairments in the upcoming type of recreational cocaine user (monthly consumption). We asked whether recreational use of cocaine impacts early attentional selection processes. Coc

  16. The emergency care of cocaine intoxications.

    NARCIS (Netherlands)

    Vroegop, M.P.; Franssen, E.J.; Voort, P.H. van der; Berg, T.N. van den; Langeweg, R.J.; Kramers, C.

    2009-01-01

    Cocaine is frequently used, especially among adolescents and by men between the age of 25 and 44. Many of them are able to use cocaine in normal day-to-day life, without any problems. Reduced prices of cocaine and other recreational drugs such as MDMA (ecstasy) and gamma hydroxybutyrate (GHB) has le

  17. Prediction of cannabis and cocaine use in adolescence using decision trees and logistic regression

    Directory of Open Access Journals (Sweden)

    Alfonso L. Palmer

    2010-01-01

    Full Text Available Spain is one of the European countries with the highest prevalence of cannabis and cocaine use among young people. The aim of this study was to investigate the factors related to the consumption of cocaine and cannabis among adolescents. A questionnaire was administered to 9,284 students between 14 and 18 years of age in Palma de Mallorca (47.1% boys and 52.9% girls whose mean age was 15.59 years. Logistic regression and decision trees were carried out in order to model the consumption of cannabis and cocaine. The results show the use of legal substances and committing fraudulence or theft are the main variables that raise the odds of consuming cannabis. In boys, cannabis consumption and a family history of drug use increase the odds of consuming cocaine, whereas in girls the use of alcohol, behaviours of fraudulence or theft and difficulty in some personal skills influence their odds of consuming cocaine. Finally, ease of access to the substance greatly raises the odds of consuming cocaine and cannabis in both genders. Decision trees highlight the role of consuming other substances and committing fraudulence or theft. The results of this study gain importance when it comes to putting into practice effective prevention programmes.

  18. Crack/cocaine users show more family problems than other substance users

    Directory of Open Access Journals (Sweden)

    Helena Ferreira Moura

    2014-07-01

    Full Text Available OBJECTIVES:To evaluate family problems among crack/cocaine users compared with alcohol and other substance users.METHODS:A cross-sectional multi-center study selected 741 current adult substance users from outpatient and inpatient Brazilian specialized clinics. Subjects were evaluated with the sixth version of the Addiction Severity Index, and 293 crack users were compared with 126 cocaine snorters and 322 alcohol and other drug users.RESULTS:Cocaine users showed more family problems when compared with other drug users, with no significant difference between routes of administration. These problems included arguing (crack 66.5%, powder cocaine 63.3%, other drugs 50.3%, p= 0.004, having trouble getting along with partners (61.5%×64.6%×48.7%, p= 0.013, and the need for additional childcare services in order to attend treatment (13.3%×10.3%×5.1%, p= 0.002. Additionally, the majority of crack/cocaine users had spent time with relatives in the last month (84.6%×86.5%×76.6%, p= 0.011.CONCLUSIONS:Brazilian treatment programs should enhance family treatment strategies, and childcare services need to be included.

  19. A Double-blind, Placebo-controlled Assessment of the Safety of Potential Interactions Between Intravenous Cocaine, Ethanol, and Oral Disulfiram

    Science.gov (United States)

    Roache, John D.; Kahn, Roberta; Newton, Thomas F.; Wallace, Christopher L.; Murff, William L.; De La Garza, Richard; Rivera, Oscar; Anderson, Ann; Mojsiak, Jurij; Elkashef, Ahmed

    2011-01-01

    BACKGROUND A majority of cocaine addicts have a comorbid alcohol use disorder. Previous studies demonstrated efficacy of disulfiram in the treatment of cocaine dependence among patients with comorbid alcohol use disorder or opioid dependence. However, the cardiac risks of a disulfiram-ethanol reaction (DER) in individuals who drink, when coupled with the cardiac effects of cocaine, could result in significant toxicity or lethality due to the 3-way drug interaction. AIMS This study examined the safety of combining cocaine (30 mg i.v.) and ethanol (0.4 g/kg i.v.) in disulfiram-treated (0, 250, and 500 mg/d, p.o.) cocaine-dependent research volunteers. RESULTS The results showed that disulfiram did not enhance the cardiovascular effects of cocaine and may have reduced the subjective high from cocaine. In contrast, ethanol produced adverse ECG changes including QTc prolongation and a DER consisting of hypotension, tachycardia, nausea, and flushing in disulfiram-treated subjects. The severity of the DER was related to disulfiram dose and the trial with 500 mg/d was stopped prematurely due to safety concerns. The DER-related hypotension and tachycardia seen with ethanol infusion alone in disulfiram-treated subjects, was not exacerbated when combined with cocaine. In fact, cocaine tended to counteract the ethanol-related hypotension though it did exacerbate the tachycardia in two of seven subjects. CONCLUSIONS Though conclusions are limited by the moderate doses of cocaine, ethanol, and disulfiram tested, the data do suggest that the risks of the moderate use of cocaine and ethanol in individuals treated with moderate doses of disulfiram (≤250 mg/d) may not be as problematic as some may assume. PMID:21696894

  20. 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.

  1. Motor and Cognitive Outcomes Through Three Years Of Age In Children Exposed To Prenatal Methamphetamine

    Science.gov (United States)

    Smith, Lynne M.; LaGasse, Linda L.; Derauf, Chris; Newman, Elana; Shah, Rizwan; Haning, William; Arria, Amelia; Huestis, Marilyn; Strauss, Arthur; Grotta, Sheri Della; Dansereau, Lynne M.; Lin, Hai; Lester, Barry M.

    2010-01-01

    Background Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. The impact of prenatal MA exposure on development in childhood is unknown. Objective To examine the effects of prenatal MA exposure on motor and cognitive development in children at 1, 2, and 3 years of age. Design/Methods IDEAL enrolled 412 mother-infant pairs at four sites (Tulsa OK, Des Moines IA, Los Angeles CA, and Honolulu HI). MA subjects (n=204) were identified by self-report or GC/MS confirmation of amphetamine and metabolites in infant meconium. Comparison subjects (n=208) were matched (race, birth weight, maternal education, type of insurance), denied amphetamine use, and had a negative meconium screen. Both groups included prenatal alcohol, tobacco and marijuana use, but excluded use of opiates, lysergic acid diethylamide, phencyclidine or cocaine only. The Peabody Developmental Motor Scales (PDMS-2) were administered to the infants at the 1 and 3 year visits. This analysis includes a subsample (n=350) of the IDEAL study with completed 1 and/or 3 year visits (n= 330 and 281, respectively). At each annual visit we also conducted the Bayley Scales of Infant Development (BSID-II) as a general evaluation of mental and motor development. The BSID-II analysis includes a subsample (n=356) of the IDEAL study with completed 1, 2, and/or 3 year visits (n= 331, 288, and 278 respectively). GLM analysis conducted on the PDMS-2 and BSID-II examined the effects of MA exposure and heavy MA exposure (≥3 days of use/week), with and without covariates. Longitudinal analyses were used to examine the effects of MA exposure on changes in motor and cognitive performance over time. Results Heavy MA exposure was associated with significantly lower grasping scores than some and no use at 1 year (P = 0.018). In longitudinal analysis, lower grasping scores associated with any MA exposure and heavy exposure persisted to 3 years. There were no effects of MA exposure, including

  2. [Neurologic complications of cocaine abuse].

    Science.gov (United States)

    Van Viet, H; Chevalier, P; Sereni, C; Bornet, P; Bautier, P; Degos, C F; Rullière, R

    1990-06-02

    Cocaine is increasingly used by drug addicts. It is considered harmless, but numerous, varied and often serious complications due to its abuse have been published. Among these, neurological complications are in the forefront. They include generalized or partial epileptic seizures, ischaemic or haemorrhagic cerebral vascular accidents, visual loss caused by optic neuropathy or by retinal artery occlusion, headaches and exacerbation of tics. Infections of the central nervous system are possible via endocarditis or septicaemia of venous or nasal origin. Neurological disorders may also occur as a consequence of a major cardiovascular complication induced by cocaine (myocardial infarction and/or dysrhythmia, aortic dissection). These neurological complications are unpredictable, and they weigh heavily on the functional and sometimes vital prognosis in habitual or occasional cocaine abusers.

  3. Brugada Pattern Electrocardiogram Unmasked with Cocaine Ingestion

    Directory of Open Access Journals (Sweden)

    M. Chadi Alraies

    2013-01-01

    Full Text Available Cocaine is considered a leading cause of drug-related deaths. This is usually sudden, unwitnessed, and without prodromal features. It has been reported that in-hospital mortality is close to 2%. Cocaine has powerful central nervous system effects1 and acute cocaine overdose has been associated with hyperthermia, agitation, paranoid ideation, status epilepticus, ventricular fibrillation, ventricular tachycardia, and myocardial infarction (MI. The mechanisms of cocaine-related death remain poorly understood. We report a patient who survived massive cocaine ingestion with psychomotor agitation and generalized seizures followed by asystolic cardiac arrest and transient Brugada pattern on electrocardiogram (ECG.

  4. Cocaine distribution in wild Erythroxylum species.

    Science.gov (United States)

    Bieri, Stefan; Brachet, Anne; Veuthey, Jean-Luc; Christen, Philippe

    2006-02-20

    Cocaine distribution was studied in leaves of wild Erythroxylum species originating from Bolivia, Brazil, Ecuador, Paraguay, Peru, Mexico, USA, Venezuela and Mauritius. Among 51 species, 28 had never been phytochemically investigated before. Cocaine was efficiently and rapidly extracted with methanol, using focused microwaves at atmospheric pressure, and analysed without any further purification by capillary gas chromatography coupled to mass spectrometry. Cocaine was reported for the first time in 14 species. Erythroxylum laetevirens was the wild species with the highest cocaine content. Its qualitative chromatographic profile also revealed other characteristic tropane alkaloids. Finally, its cocaine content was compared to those of two cultivated coca plants as well as with a coca tea bag sample.

  5. Multiple Gastrointestinal Complications of Crack Cocaine Abuse

    Directory of Open Access Journals (Sweden)

    Neal Carlin

    2014-01-01

    Full Text Available Cocaine and its alkaloid free base “crack-cocaine” have long since been substances of abuse. Drug abuse of cocaine via oral, inhalation, intravenous, and intranasal intake has famously been associated with a number of medical complications. Intestinal ischemia and perforation remain the most common manifestations of cocaine associated gastrointestinal disease and have historically been associated with oral intake of cocaine. Here we find a rare case of two relatively uncommon gastrointestinal complications of hemorrhage and pancreatitis presenting within a single admission in a chronic crack cocaine abuser.

  6. Cocaine use and the breastfeeding mother.

    Science.gov (United States)

    Jones, Wendy

    2015-01-01

    Cocaine is the second most commonly used illicit drug. Use in pregnancy and breastfeeding may have severe consequences for the baby due to its pharmacokinetic properties. Midwives need to be aware of the prolonged action of cocaine and be alert to the possibility of cocaine toxicity if a baby is excessively irritable and tachycardic. Euphoric highs are brief but breast milk and urine remain positive for long periods. Infant urine following exposure to cocaine via breast milk may remain positive for up to 60 hours. Mothers who snort cocaine should pump and dump breast milk for 24-48 hours. Passive inhalation of crack cocaine smoke may also result in infants with positive toxicology screens. Cocaine powder should never be applied to the nipples of breastfeeding mothers.

  7. Cocaine Hoppers : The Nigerian Involvement in the Global Cocaine Trade

    NARCIS (Netherlands)

    Oboh, Jude Roys

    2016-01-01

    In recent decades, Nigerian criminal drug ‘barons’ and ‘gangs’ have come to dominate international cocaine trafficking via West Africa to destination countries globally, a trend that presents a serious security threat to Africa and the world. This work provides empirical evidence to define and

  8. Cocaine Hoppers : The Nigerian Involvement in the Global Cocaine Trade

    NARCIS (Netherlands)

    Oboh, Jude Roys

    2016-01-01

    In recent decades, Nigerian criminal drug ‘barons’ and ‘gangs’ have come to dominate international cocaine trafficking via West Africa to destination countries globally, a trend that presents a serious security threat to Africa and the world. This work provides empirical evidence to define and expla

  9. Psychiatric comorbidity in a sample of cocaine-dependent outpatients seen in the Community of Madrid drug addiction care network.

    Science.gov (United States)

    Martínez-Gras, Isabel; Ferre Navarrete, Francisco; Pascual Arriazu, Jesús; Peñas Pascual, José; de Iceta Ruiz de Gauna, Mariano; Fraguas Herráez, David; Rubio Valladolid, Gabriel

    2016-03-02

    The objective of this study was to estimate the current prevalence of psychiatric disorders in cocaine-dependent patients who attend different treatment centres in the Community of Madrid. A prospective multicentre study was used, and a total of 197 cocaine-dependent subjects were assessed. The assessment instrument used for diagnosis was the Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV). The main findings of this study were a high prevalence of psychiatric comorbidity in cocaine-dependent patients seeking treatment (64.0%). The most common Non Substance Use Disorders found were attention-deficit/hyperactivity Disorders (34.5%) and depressive disorders (13.7%). The most common Substance Use Disorder was alcohol dependence (28.4%). Cocaine-dependent patients who had a depressive disorder and were alcohol dependent presented a more severe clinical profile and a higher degree of psychopathology, measured using different assessment tools, than the patients who were only cocaine dependent. These data suggest that the presence of psychiatric comorbidity could constitute a risk factor associated with the severity of cocaine dependence. The clinical heterogeneity found also indicates the need to search for individualised treatments that more specifically fit the needs of this population.

  10. Effects of Disulfiram on QTc Interval in non-Opioid Dependent and Methadone-Treated Cocaine Dependent Patients

    Science.gov (United States)

    Atkinson, Thomas S.; Sanders, Nichole; Mancino, Michael; Oliveto, Alison

    2013-01-01

    Objectives Methadone and cocaine are each known to prolong the QTc interval, a risk factor for developing potentially fatal cardiac arrhythmias. Disulfiram, often administered in the context of methadone maintenance to facilitate alcohol abstinence, has been shown to have some efficacy for cocaine dependence. Disulfiram has differential effects on cocaine and methadone metabolism, but its impact on methadone- or cocaine-induced changes in QTc interval is unclear. Thus, the effects of disulfiram on QTc interval in a subset of cocaine dependent patients participating in a 14 week, randomized, double blind, placebo-controlled clinical trial of disulfiram was prospectively determined. Methods Opioid dependent participants were inducted onto methadone (wks 1-2; MT) and both MT and nonopioid dependent (UT) participants were randomized to receive disulfiram (wks 3-14) at one of the following doses: 0, 250, 375, or 500 mg/day. Electrocardiograms (ECGs) were obtained prior to study entry and during weeks 2 and 4. Results Complete QTc interval data in 23 MT and 18 UT participants were analyzed. QTc interval tended to be higher in MT relative to UT dependent participants, regardless of disulfiram dose and time point, but disulfiram did not differentially alter QTc interval. QTc interval was, however, significantly greater in participants with recent cocaine use than those with no recent use. Conclusions These results suggest that cocaine use and possibly MT status, but not disulfiram, are risk factors for QTc prolongation. PMID:23648640

  11. Normas percibidas por los estudiantes universitarios hondureños acerca de sus pares y el uso de tabaco, alcohol, marihuana y cocaína Normas percebidas pelos estudantes universitários hondurenhos sobre os pares e o uso de tabaco, álcool, maconha e cocaína Perceived norms among honduran university students about peers and tobacco, alcohol, marijuana and cocaine use

    Directory of Open Access Journals (Sweden)

    Syntia Dinora Santos Figueroa

    2009-01-01

    alcohol at least once in a lifetime and 28% stated being daily users. Students perceived that 62% of their peers used tobacco and 63% used alcohol. The perceived norm for drug use was slightly higher in women than in men. In conclusion, there is an overestimation between the perceived norm and use of alcohol, tobacco, marijuana and cocaine.

  12. Pulmonary alterations in cocaine users

    Directory of Open Access Journals (Sweden)

    Mário Terra Filho

    Full Text Available CONTEXT: Brazilian researchers have recently recognized a marked increase in the number of people using abusable drugs and the consequences of this habit. It has become a major public health problem in a potentially productive segment of the general population. In the last few years, several medical articles have given special emphasis to pulmonary complications related to cocaine use. This review is based on this information and experience acquired with groups of cocaine users. OBJECTIVE: To present to physicians the pulmonary aspects of cocaine use and warn about the various effects this drug has on the respiratory system, stressing those related to long-term use. DESIGN: Narrative review. METHOD: Pulmonary complications are described. These may include infections (Staphylococcus aureus, pulmonary tuberculosis, acquired immunodeficiency syndrome/aids, etc., aspiration pneumonia, lung abscess, empyema, septic embolism, non-cardiogenic pulmonary edema, barotrauma, pulmonary granulomatosis, bronchiolitis obliterans and organizing pneumonia, pneumonitis and interstitial fibrosis, pneumonitis hypersensitivity, lung infiltrates and eosinophilia in individuals with bronchial hyperreactivity, diffuse alveolar hemorrhage, vasculitis, pulmonary infarction, pulmonary hypertension and alterations in gas exchange. It is concluded that physicians should give special attention to the various pulmonary and clinical manifestations related to cocaine use, particularly in young patients.

  13. Characteristics and behaviors of mothers who have a child with fetal alcohol syndrome.

    Science.gov (United States)

    Cannon, Michael J; Dominique, Yvette; O'Leary, Leslie A; Sniezek, Joseph E; Floyd, R Louise

    2012-01-01

    Fetal alcohol syndrome (FAS) is a leading cause of birth defects and developmental disabilities. The objective of this study was to identify the characteristics and behaviors of mothers of children with FAS in the United States using population-based data from the FAS Surveillance Network (FASSNet). FASSNet used a multiple source methodology that identified FAS cases through passive reporting and active review of records from hospitals, specialty clinics, private physicians, early intervention programs, Medicaid, birth certificates and other vital records, birth defects surveillance programs, and hospital discharge data. The surveillance included children born during January 1, 1995-December 31, 1997. In the four states included in our analysis - Arizona, New York, Alaska, and Colorado - there were 257 confirmed cases and 96 probable cases for a total of 353 FAS cases. Compared to all mothers in the states where surveillance occurred, mothers of children with FAS were significantly more likely to be older, American Indians/Alaska Natives, Black, not Hispanic, unmarried, unemployed, and without prenatal care, to smoke during pregnancy, to have a lower educational level, and to have more live born children. A significant proportion of mothers (9-29%) had another child with suspected alcohol effects. Compared to all US mothers, they were also significantly more likely to be on public assistance, to be on Medicaid at their child's birth, to have received treatment for alcohol abuse, to have confirmed alcoholism, to have used marijuana or cocaine during pregnancy, to have their baby screen positive for alcohol or drugs at birth, to have had an induced abortion, to have had a history of mental illness, to have been involved in binge drinking during pregnancy, and to have drunk heavily (7 days/week) during pregnancy. These findings suggest that it is possible to identify women who are at high risk of having a child with FAS and target these women for interventions.

  14. Acute brain metabolic effects of cocaine in rhesus monkeys with a history of cocaine use.

    Science.gov (United States)

    Henry, Porche' Kirkland; Murnane, Kevin S; Votaw, John R; Howell, Leonard L

    2010-12-01

    Cocaine addiction involves an escalation in drug intake which alters many brain functions. The present study documented cocaine-induced changes in brain metabolic activity as a function of cocaine self-administration history. Experimentally naive rhesus monkeys (N = 6) were given increasing access to cocaine under a fixed-ratio schedule of intravenous (i.v.) drug self-administration. PET imaging with F-18 labeled fluorodeoxyglucose (FDG) was used to measure acute intramuscular (i.m.) cocaine-induced changes in brain metabolism in the cocaine-naïve state, following 60 sessions under limited-access conditions (1 h/day), following 60 sessions under extended-access conditions (4 h/day), and following 4 weeks of drug withdrawal. In the cocaine-naïve state, cocaine-induced increases in brain metabolism were restricted to the prefrontal cortex. As cocaine exposure increased from limited to extended access, metabolic effects expanded throughout the frontal cortex and were induced within the striatum. Conversely, cocaine-induced activation was far less robust following withdrawal. The results highlight a progressive expansion of the metabolic effects of cocaine to include previously unaffected dopamine innervated brain regions as a consequence of cocaine self-administration history. The identification of brain regions progressively influenced by drug exposure may be highly relevant toward efforts to develop treatments for cocaine addiction.

  15. Metabolic Enzymes of Cocaine Metabolite Benzoylecgonine.

    Science.gov (United States)

    Chen, Xiabin; Zheng, Xirong; Zhan, Max; Zhou, Ziyuan; Zhan, Chang-Guo; Zheng, Fang

    2016-08-19

    Cocaine is one of the most addictive drugs without a U.S. Food and Drug Administration (FDA)-approved medication. Enzyme therapy using an efficient cocaine-metabolizing enzyme is recognized as the most promising approach to cocaine overdose treatment. The actual enzyme, known as RBP-8000, under current clinical development for cocaine overdose treatment is our previously designed T172R/G173Q mutant of bacterial cocaine esterase (CocE). The T172R/G173Q mutant is effective in hydrolyzing cocaine but inactive against benzoylecgonine (a major, biologically active metabolite of cocaine). Unlike cocaine itself, benzoylecgonine has an unusually stable zwitterion structure resistant to further hydrolysis in the body and environment. In fact, benzoylecgonine can last in the body for a very long time (a few days) and, thus, is responsible for the long-term toxicity of cocaine and a commonly used marker for drug addiction diagnosis in pre-employment drug tests. Because CocE and its mutants are all active against cocaine and inactive against benzoylecgonine, one might simply assume that other enzymes that are active against cocaine are also inactive against benzoylecgonine. Here, through combined computational modeling and experimental studies, we demonstrate for the first time that human butyrylcholinesterase (BChE) is actually active against benzoylecgonine, and that a rationally designed BChE mutant can not only more efficiently accelerate cocaine hydrolysis but also significantly hydrolyze benzoylecgonine in vitro and in vivo. This sets the stage for advanced studies to design more efficient mutant enzymes valuable for the development of an ideal cocaine overdose enzyme therapy and for benzoylecgonine detoxification in the environment.

  16. Glycosylation defects underlying fetal alcohol spectrum disorder: a novel pathogenetic model. "When the wine goes in, strange things come out" - S.T. Coleridge, The Piccolomini.

    NARCIS (Netherlands)

    Binkhorst, M.; Wortmann, S.B.; Funke, S.; Kozicz, T.L.; Wevers, R.A.; Morava, E.

    2012-01-01

    Fetal alcohol spectrum disorder (FASD) is an umbrella term used to describe the craniofacial dysmorphic features, malformations, and disturbances in growth, neurodevelopment and behavior occurring in individuals prenatally exposed to alcohol. Fetal alcohol syndrome (FAS) represents the severe end of

  17. Sex differences in cocaine-dependent individuals’ response to disulfiram treatment

    Science.gov (United States)

    Nich, Charla; McCance-Katz, Elinore F.; Petrakis, Ismene L.; Cubells, Joseph F.; Rounsaville, Bruce J.; Carroll, Kathleen M.

    2013-01-01

    The objective of this study is to evaluate differential response to disulfiram treatment of cocaine dependence by sex. Sex by treatment interactions from two pooled randomized clinical trials involving 191 cocaine-dependent subjects (36% female) were evaluated. Primary outcomes were days of abstinence and percentage of drug-free urine specimens. Significant sex by treatment interactions were found, where men treated with disulfiram had better outcomes than those who were not. Women had an intermediate outcome regardless of whether they received disulfiram. Sex differences in response to disulfiram treatment have important clinical and theoretical implications. Reasons for this apparent sex-based response are not clear, but possible mechanisms worthy of greater study include differences in alcohol use by sex as well as differences in dopamine-mediated responses to cocaine and disulfiram. PMID:15236812

  18. Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine's action in vivo

    OpenAIRE

    Tallarida, Christopher S.; Egan, Erin; Alejo, Gissel D.; Raffa, Robert; Tallarida, Ronald J.; Rawls, Scott M.

    2014-01-01

    Levamisole is estimated by the Drug Enforcement Agency (DEA) to be present in about 80% of cocaine seized in the United States and linked to debilitating, and sometimes fatal, immunologic effects in cocaine abusers. One explanation for the addition of levamisole to cocaine is that it increases the amount of product and enhances profits. An alternative possibility, and one investigated here, is that levamisole alters cocaine's action in vivo. We specifically investigated effects of levamisole ...

  19. Prenatal screening and genetics

    DEFF Research Database (Denmark)

    Alderson, P; Aro, A R; Dragonas, T

    2001-01-01

    Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we...... examine definitions of the relevant concepts in order to illustrate this point. The concepts are i) prenatal, ii) genetic screening, iii) screening, scanning and testing, iv) maternal and foetal tests, v) test techniques and vi) genetic conditions. So far, prenatal screening has little connection...... with precisely defined genetics. There are benefits but also disadvantages in overstating current links between them in the term genetic screening. Policy making and professional and public understandings about screening could be clarified if the distinct meanings of prenatal screening and genetic screening were...

  20. Prenatal Genetic Screening Tests

    Science.gov (United States)

    ... cells from the fetus or placenta obtained through amniocentesis or chorionic villus sampling (CVS) . FAQ164 “Prenatal Genetic ... should be followed by a diagnostic test with amniocentesis or CVS. The cell-free DNA screening test ...

  1. Preventing Abuse of Drugs, Alcohol, and Tobacco by Adolescents.

    Science.gov (United States)

    Falco, Mathea

    From the mid-1960s until 1980, adolescent drug use rose sharply. Although use has declined somewhat since, adolescent cocaine use remains at peak levels, and crack presents a major threat. Treatment for compulsive drug or alcohol use is needed by 5 to 15 percent of the teenagers who experiment with drugs and alcohol. Drug abuse experts now believe…

  2. Impaired insight in cocaine addiction: laboratory evidence and effects on cocaine-seeking behaviour

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, S.J.; Moeller, S.J.; Maloney, T.; Parvaz, M.A.; Alia-Klein, N.; Woicik, P.A.; Telang, F.; Wang, G.-J.; Volkow, N.D.; Goldstein, R.Z.

    2010-04-15

    Neuropsychiatric disorders are often characterized by impaired insight into behaviour. Such an insight deficit has been suggested, but never directly tested, in drug addiction. Here we tested for the first time this impaired insight hypothesis in drug addiction, and examined its potential association with drug-seeking behaviour. We also tested potential modulation of these effects by cocaine urine status, an individual difference known to impact underlying cognitive functions and prognosis. Sixteen cocaine addicted individuals testing positive for cocaine in urine, 26 cocaine addicted individuals testing negative for cocaine in urine, and 23 healthy controls completed a probabilistic choice task that assessed objective preference for viewing four types of pictures (pleasant, unpleasant, neutral and cocaine). This choice task concluded by asking subjects to report their most selected picture type; correspondence between subjects self-reports with their objective choice behaviour provided our index of behavioural insight. Results showed that the urine positive cocaine subjects exhibited impaired insight into their own choice behaviour compared with healthy controls; this same study group also selected the most cocaine pictures (and fewest pleasant pictures) for viewing. Importantly, however, it was the urine negative cocaine subjects whose behaviour was most influenced by insight, such that impaired insight in this subgroup only was associated with higher cocaine-related choice on the task and more severe actual cocaine use. These findings suggest that interventions to enhance insight may decrease drug-seeking behaviour, especially in urine negative cocaine subjects, potentially to improve their longer-term clinical outcomes.

  3. Cocaine self-administration disrupts mesolimbic dopamine circuit function and attenuates dopaminergic responsiveness to cocaine.

    Science.gov (United States)

    Siciliano, Cody A; Ferris, Mark J; Jones, Sara R

    2015-08-01

    Dopaminergic projections from the ventral midbrain to the nucleus accumbens (NAc) have long been implicated in encoding associations between reward availability and environmental stimuli. As such, this circuit is instrumental in guiding behaviors towards obtaining maximal rewards based on previous experience. Cocaine acts on the dopamine system to exert its reinforcing effects and it is thought that cocaine-induced dysregulation of dopamine neurotransmission contributes to the difficulty that cocaine addicts exhibit in selecting environmentally appropriate behaviors. Here we used cocaine self-administration combined with in vivo fast scan cyclic voltammetry in anesthetised rats to examine the function of the ventral tegmental area to NAc projection neurons. Over 5 days of cocaine self-administration (fixed-ratio 1; 1.5 mg/kg/injection; 40 injections/day), animals increased their rate of intake. Following cocaine self-administration, there was a marked reduction in ventral tegmental area-stimulated NAc dopamine release. Additionally, there was a decreased augmentation of stimulated dopamine overflow in response to a cocaine challenge. These findings demonstrate that cocaine induces a hypodopaminergic state, which may contribute to the inflexible drug-taking and drug-seeking behaviors observed in cocaine abusers. Additionally, tolerance to the ability of cocaine to elevate dopamine may lead to increased cocaine intake in order to overcome decreased effects, another hallmark of cocaine abuse. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  4. Quality of life, social functioning, family structure, and treatment history associated with crack cocaine use in youth from the general population

    OpenAIRE

    Narvaez,Joana C.M.; Flávio Pechansky; Karen Jansen; Ricardo T. Pinheiro; Ricardo A. Silva; Flávio Kapczinski; Pedro V Magalhães

    2015-01-01

    Objective:To assess the relationship between crack cocaine use and dimensions of quality of life and social functioning in young adults.Methods:This was a cross-sectional, population-based study involving 1,560 participants in Pelotas, Brazil. Crack cocaine use and abuse were investigated using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) inventory. Outcomes of interest were quality of life, religiosity, and social functioning in terms of education, occupational stat...

  5. The meta-chlorophenylpiperazine challenge test in cocaine addicts: hormonal and psychological responses.

    Science.gov (United States)

    Buydens-Branchey, L; Branchey, M; Fergeson, P; Hudson, J; McKernin, C

    1997-06-01

    We report on the neuroendocrine and psychological responsivity of 31 cocaine addicts and 14 controls to the serotonergic agonist, meta-chlorophenylpiperazine (m-CPP) (0.5 mg/kg p.o.). Cocaine addicts were subdivided into subjects with aggressive tendencies and other features similar to those found in type 2 alcoholics and subjects without these features. Following m-CPP, aggressive and nonaggressive patients had a significantly blunted prolactin response compared to controls, but there was no difference between the two patient subgroups. There was no difference between the cortisol responses of nonaggressive patients and controls, but aggressive patients had a significantly blunted cortisol response compared to controls and nonaggressive patients. Both patient subgroups reported more intense "activation-euphoria" and "high" responses following m-CPP than controls. These results could indicate the existence of alterations along serotonergic pathways in cocaine addicts taken as a group. In addition, a subgroup of patients who could be described as type 2 cocaine addicts appear to be biologically different from healthy subjects and from other cocaine addicts as indicated by a greater cortisol blunting following m-CPP.

  6. Reaction Mechanism for Cocaine Esterase-Catalyzed Hydrolyses of (+)- and (−)-Cocaine: Unexpected Common Rate-Determining Step

    OpenAIRE

    Liu, Junjun; Zhao, Xinyun; Yang, Wenchao; Zhan, Chang-Guo

    2011-01-01

    First-principles quantum mechanical/molecular mechanical (QM/MM)-free energy (FE) calculations have been performed to examine catalytic mechanism for cocaine esterase (CocE)-catalyzed hydrolysis of (+)-cocaine in comparison with CocE-catalyzed hydrolysis of (−)-cocaine. It has been shown that the acylation of (+)-cocaine consists of nucleophilic attack of hydroxyl group of Ser117 on carbonyl carbon of (+)-cocaine benzoyl ester and the dissociation of (+)-cocaine benzoyl ester. The first react...

  7. Cocaine challenge enhances release of neuroprotective amino acid taurine in the striatum of chronic cocaine treated rats: a microdialysis study

    OpenAIRE

    Yablonsky-Alter, Elena; Agovic, Mervan S.; Gashi, Eleonora; Lidsky, Theodore I.; Friedman, Eitan; Banerjee, Shailesh P.

    2009-01-01

    Drug addiction is a serious public health problem. There is increasing evidence on the involvement of augmented glutamatergic transmission in cocaine-induced addiction and neurotoxicity. We investigated effects of acute or chronic cocaine administration and cocaine challenge following chronic cocaine exposure on the release of excitotoxic glutamate and neuroprotective taurine in the rat striatum by microdialysis. Cocaine challenge, following withdrawal after repeated cocaine exposure markedly...

  8. An antidote for acute cocaine toxicity.

    Science.gov (United States)

    Treweek, Jennifer B; Janda, Kim D

    2012-04-02

    Not only has immunopharmacotherapy grown into a field that addresses the abuse of numerous illicit substances, but also the treatment methodologies within immunopharmacotherapy have expanded from traditional active vaccination to passive immunization with anti-drug monoclonal antibodies, optimized mAb formats, and catalytic drug-degrading antibodies. Many laboratories have focused on transitioning distinct immunopharmacotherapeutics to clinical evaluation, but with respect to the indication of cocaine abuse, only the active vaccine TA-CD, which is modeled after our original cocaine hapten GNC, has been carried through to human clinical trials. The successful application of murine mAb GNC92H2 to the reversal of cocaine overdose in a mouse model prompted investigations of human immunoglobulins with the clinical potential to serve as cocaine antidotes. We now report the therapeutic utility of a superior clone, human mAb GNCgzk (K(d) = 0.18 nM), which offers a 10-fold improvement in cocaine binding affinity. The GNCgzk manifold was engineered for rapid cocaine clearance, and administration of the F(ab')₂ and Fab formats even after the appearance of acute behavioral signs of cocaine toxicity granted nearly complete prevention of lethality. Thus, contrary to the immunopharmacotherapeutic treatment of drug self-administration, minimal antibody doses were shown to counteract the lethality of a molar excess of circulating cocaine. Passive vaccination with drug-specific antibodies represents a viable treatment strategy for the human condition of cocaine overdose.

  9. Molecular approaches to treatments for cocaine abuse

    Science.gov (United States)

    Flippen-Anderson, Judith L.; George, Clifford; Deschamps, Jeffrey R.

    2003-02-01

    Cocaine is a potent stimulant of the central nervous system with severe addiction potential. Its abuse is a major problem worldwide. The exact mechanism of action of cocaine is still uncertain but it is known that its reinforcing and stimulant effects are related to its ability to inhibit the membrane bound dopamine transporter (DAT). This paper discusses efforts that are underway to identify ligands for possible use in the treatment of cocaine abuse. Much of this effort has been focussed on understanding cocaine interactions at DAT receptor sites.

  10. Neuroimaging and Fetal Alcohol Spectrum Disorders

    Science.gov (United States)

    Norman, Andria L.; Crocker, Nicole; Mattson, Sarah N.; Riley, Edward P.

    2009-01-01

    The detrimental effects of prenatal alcohol exposure on the developing brain include structural brain anomalies as well as cognitive and behavioral deficits. Initial neuroimaging studies of fetal alcohol spectrum disorders (FASD) using magnetic resonance imaging (MRI) confirmed previous autopsy reports of overall reduction in brain volume and…

  11. Comparing exponential and exponentiated models of drug demand in cocaine users.

    Science.gov (United States)

    Strickland, Justin C; Lile, Joshua A; Rush, Craig R; Stoops, William W

    2016-12-01

    Drug purchase tasks provide rapid and efficient measurement of drug demand. Zero values (i.e., prices with zero consumption) present a quantitative challenge when using exponential demand models that exponentiated models may resolve. We aimed to replicate and advance the utility of using an exponentiated model by demonstrating construct validity (i.e., association with real-world drug use) and generalizability across drug commodities. Participants (N = 40 cocaine-using adults) completed Cocaine, Alcohol, and Cigarette Purchase Tasks evaluating hypothetical consumption across changes in price. Exponentiated and exponential models were fit to these data using different treatments of zero consumption values, including retaining zeros or replacing them with 0.1, 0.01, or 0.001. Excellent model fits were observed with the exponentiated model. Means and precision fluctuated with different replacement values when using the exponential model but were consistent for the exponentiated model. The exponentiated model provided the strongest correlation between derived demand intensity (Q0) and self-reported free consumption in all instances (Cocaine r = .88; Alcohol r = .97; Cigarette r = .91). Cocaine demand elasticity was positively correlated with alcohol and cigarette elasticity. Exponentiated parameters were associated with real-world drug use (e.g., weekly cocaine use) whereas these correlations were less consistent for exponential parameters. Our findings show that selection of zero replacement values affects demand parameters and their association with drug-use outcomes when using the exponential model but not the exponentiated model. This work supports the adoption of the exponentiated demand model by replicating improved fit and consistency and demonstrating construct validity and generalizability. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  12. [Cocaine-related gastric perforation].

    Science.gov (United States)

    Ring, A; Stein, E; Stern, J

    2010-06-01

    Since the 1980s the abuse of cocaine has been -associated with gastroduodenal perforations in the United States. Here, we report the case of a 28-year-old man who came to our hospital with severe abdominal pain after smoking cocaine. Physical examination revealed generalised abdominal guarding. His X-ray did not show any free intraperitoneal air. However, there was a slightly elevated white blood cell count. Upon laparoscopic exploration of the abdomen, the -patient was found to have a generalised peritonitis secondary to a perforation of the prepyloric anterior wall. The operative procedure consisted of ulcer excision and primary closure with a pyloroplasty as well as an extensive abdominal irrigation after laparotomy.

  13. Intense sweetness surpasses cocaine reward.

    Directory of Open Access Journals (Sweden)

    Magalie Lenoir

    Full Text Available BACKGROUND: Refined sugars (e.g., sucrose, fructose were absent in the diet of most people until very recently in human history. Today overconsumption of diets rich in sugars contributes together with other factors to drive the current obesity epidemic. Overconsumption of sugar-dense foods or beverages is initially motivated by the pleasure of sweet taste and is often compared to drug addiction. Though there are many biological commonalities between sweetened diets and drugs of abuse, the addictive potential of the former relative to the latter is currently unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that when rats were allowed to choose mutually-exclusively between water sweetened with saccharin-an intense calorie-free sweetener-and intravenous cocaine-a highly addictive and harmful substance-the large majority of animals (94% preferred the sweet taste of saccharin. The preference for saccharin was not attributable to its unnatural ability to induce sweetness without calories because the same preference was also observed with sucrose, a natural sugar. Finally, the preference for saccharin was not surmountable by increasing doses of cocaine and was observed despite either cocaine intoxication, sensitization or intake escalation-the latter being a hallmark of drug addiction. CONCLUSIONS: Our findings clearly demonstrate that intense sweetness can surpass cocaine reward, even in drug-sensitized and -addicted individuals. We speculate that the addictive potential of intense sweetness results from an inborn hypersensitivity to sweet tastants. In most mammals, including rats and humans, sweet receptors evolved in ancestral environments poor in sugars and are thus not adapted to high concentrations of sweet tastants. The supranormal stimulation of these receptors by sugar-rich diets, such as those now widely available in modern societies, would generate a supranormal reward signal in the brain, with the potential to override self

  14. Stimulation of 5-HT(1B) receptors enhances cocaine reinforcement yet reduces cocaine-seeking behavior.

    Science.gov (United States)

    Pentkowski, Nathan S; Acosta, Jazmin I; Browning, Jenny R; Hamilton, Elizabeth C; Neisewander, Janet L

    2009-09-01

    Paradoxically, stimulation of 5-HT(1B) receptors (5-HT(1B)Rs) enhances sensitivity to the reinforcing effects of cocaine but attenuates incentive motivation for cocaine as measured using the extinction/reinstatement model. We revisited this issue by examining the effects of a 5-HT(1B)R agonist, CP94253, on cocaine reinforcement and cocaine-primed reinstatement, predicting that CP94253 would enhance cocaine-seeking behavior reinstated by a low priming dose, similar to its effect on cocaine reinforcement. Rats were trained to self-administer cocaine (0.75 mg/kg, i.v.) paired with light and tone cues. For reinstatement experiments, they then underwent daily extinction training to reduce cocaine-seeking behavior (operant responses without cocaine reinforcement). Next, they were pre-treated with CP94253 (3-10 mg/kg, s.c.) and either tested for cocaine-primed (10 or 2.5 mg/kg, i.p.) or cue-elicited reinstatement of extinguished cocaine-seeking behavior. For reinforcement, effects of CP94253 (5.6 mg/kg) across a range of self-administered cocaine doses (0-1.5 mg/kg, i.v.) were examined. Cocaine dose-dependently reinstated cocaine-seeking behavior, but contrary to our prediction, CP94253 reduced reinstatement with both priming doses. Similarly, CP94253 reduced cue-elicited reinstatement. In contrast, CP94253 shifted the self-administration dose-effect curve leftward, consistent with enhanced cocaine reinforcement. When saline was substituted for cocaine, CP94253 reduced response rates (i.e. cocaine-seeking behavior). In subsequent control experiments, CP94253 decreased open-arm exploration in an elevated plus-maze suggesting an anxiogenic effect, but had no effect on locomotion or sucrose reinforcement. These results provide strong evidence that stimulation of 5-HT(1B)Rs produces opposite effects on cocaine reinforcement and cocaine-seeking behavior, and further suggest that 5-HT(1B)Rs may be a novel target for developing medications for cocaine dependence.

  15. Diazepam alters cocaine self-administration, but not cocaine-stimulated locomotion or nucleus accumbens dopamine

    OpenAIRE

    2008-01-01

    Cocaine is known to enhance nucleus accumbens dopamine (NAcc DA), serve as a positive reinforcer and produce negative effects, such as anxiety. The influence of diazepam on cocaine intake, cocaine-stimulated behavioral activity and NAcc DA was investigated using self-administration and experimenter-administered intravenous (i.v.) cocaine. In Experiment 1, rats were pretreated with diazepam (0.25 mg/kg) or saline (0.1 ml) 30 minutes prior to 20 daily 1-hr cocaine (0.75 mg/kg/inj) self-administ...

  16. Alcohol, Other Drugs, and Obesity: Plan-of-the-Day Notes

    Science.gov (United States)

    1992-05-01

    What Are The Signs of Alcoholism 29 LSD 31 Anabolic Steroids 32 Alcohol 33 Amphetamines 34 Cocaine 35 Marijuana 36 PCP 37 Narcotics 38 End Notes 39...drug. Alcohol can change how a person thinks, feels and acts. Anyone can become addicted to alcohol if he or she drinks enough of it over a long enough...Adolescents become addicted to alcohol more quickly than do adults because they are still developing physiologically and psychologically. This maturation

  17. Manipulating a "cocaine engram" in mice.

    Science.gov (United States)

    Hsiang, Hwa-Lin Liz; Epp, Jonathan R; van den Oever, Michel C; Yan, Chen; Rashid, Asim J; Insel, Nathan; Ye, Li; Niibori, Yosuke; Deisseroth, Karl; Frankland, Paul W; Josselyn, Sheena A

    2014-10-15

    Experience with drugs of abuse (such as cocaine) produces powerful, long-lasting memories that may be important in the development and persistence of drug addiction. The neural mechanisms that mediate how and where these cocaine memories are encoded, consolidated and stored are unknown. Here we used conditioned place preference in mice to examine the precise neural circuits that support the memory of a cocaine-cue association (the "cocaine memory trace" or "cocaine engram"). We found that a small population of neurons (∼10%) in the lateral nucleus of amygdala (LA) were recruited at the time of cocaine-conditioning to become part of this cocaine engram. Neurons with increased levels of the transcription factor CREB were preferentially recruited or allocated to the cocaine engram. Ablating or silencing neurons overexpressing CREB (but not a similar number of random LA neurons) before testing disrupted the expression of a previously acquired cocaine memory, suggesting that neurons overexpressing CREB become a critical hub in what is likely a larger cocaine memory engram. Consistent with theories that coordinated postencoding reactivation of neurons within an engram or cell assembly is crucial for memory consolidation (Marr, 1971; Buzsáki, 1989; Wilson and McNaughton, 1994; McClelland et al., 1995; Girardeau et al., 2009; Dupret et al., 2010; Carr et al., 2011), we also found that post-training suppression, or nondiscriminate activation, of CREB overexpressing neurons impaired consolidation of the cocaine memory. These findings reveal mechanisms underlying how and where drug memories are encoded and stored in the brain and may also inform the development of treatments for drug addiction.

  18. A thermostable bacterial cocaine esterase rapidly eliminates cocaine from brain in nonhuman primates.

    Science.gov (United States)

    Howell, L L; Nye, J A; Stehouwer, J S; Voll, R J; Mun, J; Narasimhan, D; Nichols, J; Sunahara, R; Goodman, M M; Carroll, F I; Woods, J H

    2014-07-01

    A long-acting, thermostable bacterial cocaine esterase (CocE) has been identified that rapidly degrades cocaine with a K(M) of 1.33+0.085 μM. In vivo evaluation of CocE has shown protection against convulsant and lethal effects of cocaine in rodents, confirming the therapeutic potential of CocE against cocaine overdose. However, the current study is the first to evaluate the effects of CocE on cocaine brain levels. Positron emission tomogrpahy neuroimaging of [(11)C]cocaine was used to evaluate the time course of cocaine elimination from brain in the presence and absence of CocE in nonhuman primates. Systemic administration of CocE eliminated cocaine from the rhesus-monkey brain approximately three times faster than control conditions via peripheral actions through attenuating the input function from blood plasma. The efficiency of this process is sufficient to alleviate or prevent adverse central nervous system effects induced by cocaine. Although the present study used tracer doses of cocaine to access brain clearance, these findings further support the development of CocE for the treatment of acute cocaine toxicity.

  19. Bacterial cocaine esterase: a protein-based therapy for cocaine overdose and addiction.

    Science.gov (United States)

    Narasimhan, Diwahar; Woods, James H; Sunahara, Roger K

    2012-02-01

    Cocaine is highly addictive and there are no pharmacotherapeutic drugs available to treat acute cocaine toxicity or chronic abuse. Antagonizing an inhibitor such as cocaine using a small molecule has proven difficult. The alternative approach is to modify cocaine's pharmacokinetic properties by sequestering or hydrolyzing it in serum and limiting access to its sites of action. We took advantage of a bacterial esterase (CocE) that has evolved to hydrolyze cocaine and have developed it as a therapeutic that rapidly and specifically clears cocaine from the subject. Native enzyme was unstable at 37°C, thus limiting CocE's potential. Innovative computational methods based on the protein's structure helped elucidate its mechanism of destabilization. Novel protein engineering methodologies were applied to substantially improve its stability in vitro and in vivo. These improvements rendered CocE as a powerful and efficacious therapeutic to treat cocaine intoxication and lead the way towards developing a therapy for addiction.

  20. Your First Prenatal Care Checkup

    Science.gov (United States)

    ... report card Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ... Last reviewed: May, 2011 Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ...

  1. Prenatal Care: Third Trimester Visits

    Science.gov (United States)

    Healthy Lifestyle Pregnancy week by week During the third trimester, prenatal care might include vaginal exams to check the baby's ... 2015 Original article: http://www.mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/in-depth/prenatal-care/art- ...

  2. Prenatal Care: Second Trimester Visits

    Science.gov (United States)

    Healthy Lifestyle Pregnancy week by week During the second trimester, prenatal care includes routine lab tests and measurements of your ... 2015 Original article: http://www.mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/in-depth/prenatal-care/art- ...

  3. Infección prenatal

    OpenAIRE

    Pastor Durán, Xavier

    1986-01-01

    Protocolos terapeuticos. Infección prenatal. Riesgo de infección prenatal. La infección prenatal requiere un alto índice de sospecha, ya que no siempre, los antecedentes se hallan presentes bien porque faltan o bien porque hayan pasado desapercibidos. Dentro del concepto de infección prenatal se encuentran las englobadas en el acrónimo Torches (toxoplasmosis, rubeola, citomegalovirosis, herpes o sífilis) )...

  4. 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)

  5. Levamisole-contaminated cocaine : a hairy affair

    NARCIS (Netherlands)

    van der Veer, Tjeerd; Pennings, Ed; Tervaert, J W Cohen; Korswagen, Lindy-Anne

    2015-01-01

    Levamisole-contaminated cocaine can induce severe systemic vasculitis. The diagnosis can be challenging, especially when substance abuse is uncertain. We present the case of a 42-year-old woman suffering from vasculitis due to levamisole-contaminated cocaine, who persistently denied substance abuse.

  6. Cilioretinal artery occlusion following intranasal cocaine insufflations

    Directory of Open Access Journals (Sweden)

    Balaji Kannan

    2011-01-01

    Full Text Available Cocaine is used to produce a euphoric effect by abusers, who may be unaware of the devastating systemic and ocular side effects of this drug. We describe the first known case of cilioretinal artery occlusion after intranasal cocaine abuse.

  7. A Simple Economic Model of Cocaine Production

    Science.gov (United States)

    1994-01-01

    the production dhain that are vulnerable to itr o as well as providing a clearer picture of the path that cocaine takes before reading retail markts in...In fact, given the volatility of cocaine product prices in PBC, it is probably not uncommon for segments of production to be unprofitable at times

  8. Signs of Cocaine Abuse and Addiction

    Science.gov (United States)

    ... Use and Addiction Signs of Cocaine Use and Addiction Listen ©istock.com/ AntonioGuillern After the "high" of the cocaine wears off, you can "crash" and feel tired and sad for days. You also get a strong craving to take the drug again to try to ...

  9. Evaluating the efficacy of a web-based self-help intervention with and without chat counseling in reducing the cocaine use of problematic cocaine users: the study protocol of a pragmatic three-arm randomized controlled trial.

    Science.gov (United States)

    Schaub, Michael P; Maier, Larissa J; Wenger, Andreas; Stark, Lars; Berg, Oliver; Beck, Thilo; Quednow, Boris B; Haug, Severin

    2015-07-10

    Web-based self-help interventions that aim to reduce problematic substance use are able to reach "hidden" consumer groups in the general population who often fear stigmatization and thus avoid institutional addiction treatment. In Western European countries, including Switzerland, cocaine is the most widely used psychoactive substance after alcohol, tobacco, and cannabis. Although approximately one in six users develop serious problems of dependency, only a minority seeks help from psychiatrists or in outpatient counseling centers or psychiatric hospitals. Offering web-based therapy treatment may potentially reach users who hesitate to approach institutional treatment services and help them reduce their cocaine use before they get into more serious trouble. The study will use a three-arm randomized controlled trial (RCT) design to test the efficacy of a web-based self-help intervention with or without guided chat counseling compared with that of a waiting list control condition in reducing or stopping cocaine use. The primary outcome measure will be the weekly quantity of cocaine used. Secondary outcome measures will include the number of cocaine use days in the past 30 days, the severity of cocaine dependence, the use of alcohol, tobacco, and/or other illicit drugs, changes in mental health symptoms, and treatment retention. The self-help intervention will consist of eight modules that are designed to reduce cocaine use and depression symptoms. These modules are based on the principles of Motivational Enhancement Therapy and Cognitive Behavioral Therapy, such as Behavioral Self-Management. The three individual chat therapy sessions will be based on the same therapy approaches and will be tailored to participants' self-help data and aim to assist the reinstatement of social rewards and the improvement of social support and relationships. This study will be the first RCT to test the effectiveness of a web-based self-help intervention in combination with or without

  10. Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine's action in vivo.

    Science.gov (United States)

    Tallarida, Christopher S; Egan, Erin; Alejo, Gissel D; Raffa, Robert; Tallarida, Ronald J; Rawls, Scott M

    2014-04-01

    Levamisole is estimated by the Drug Enforcement Agency (DEA) to be present in about 80% of cocaine seized in the United States and linked to debilitating, and sometimes fatal, immunologic effects in cocaine abusers. One explanation for the addition of levamisole to cocaine is that it increases the amount of product and enhances profits. An alternative possibility, and one investigated here, is that levamisole alters cocaine's action in vivo. We specifically investigated effects of levamisole on cocaine's stereotypical and place-conditioning effects in an established invertebrate (planarian) assay. Acute exposure to levamisole or cocaine produced concentration-dependent increases in stereotyped movements. For combined administration of the two agents, isobolographic analysis revealed that the observed stereotypical response was enhanced relative to the predicted effect, indicating synergism for the interaction. In conditioned place preference (CPP) experiments, cocaine produced a significant preference shift; in contrast, levamisole was ineffective at all concentrations tested. For combination experiments, a submaximal concentration of cocaine produced CPP that was enhanced by inactive concentrations of levamisole, indicating synergism. The present results provide the first experimental evidence that levamisole enhances cocaine's action in vivo. Most important is the identification of synergism for the levamisole/cocaine interaction, which now requires further study in mammals.

  11. Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine's action in vivo

    Science.gov (United States)

    Tallarida, Christopher S.; Egan, Erin; Alejo, Gissel D.; Raffa, Robert; Tallarida, Ronald J.; Rawls, Scott M.

    2014-01-01

    Levamisole is estimated by the Drug Enforcement Agency (DEA) to be present in about 80% of cocaine seized in the United States and linked to debilitating, and sometimes fatal, immunologic effects in cocaine abusers. One explanation for the addition of levamisole to cocaine is that it increases the amount of product and enhances profits. An alternative possibility, and one investigated here, is that levamisole alters cocaine's action in vivo. We specifically investigated effects of levamisole on cocaine's stereotypical and place-conditioning effects in an established invertebrate (planarian) assay. Acute exposure to levamisole or cocaine produced concentration-dependent increases in stereotyped movements. For combined administration of the two agents, isobolographic analysis revealed that the observed stereotypical response was enhanced relative to the predicted effect, indicating synergism for the interaction. In conditioned place preference (CPP) experiments, cocaine produced a significant preference shift; in contrast, levamisole was ineffective at all concentrations tested. For combination experiments, a submaximal concentration of cocaine produced CPP that was enhanced by inactive concentrations of levamisole, indicating synergism. The present results provide the first experimental evidence that levamisole enhances cocaine's action in vivo. Most important is the identification of synergism for the levamisole/cocaine interaction, which now requires further study in mammals. PMID:24440755

  12. Anorexic activity of cocaine and coca extract in naive and cocaine tolerant rats.

    Science.gov (United States)

    Vee, G L; Fink, G B; Constantine, G H

    1983-04-01

    Dose response curves for reducing limited access food consumption were determined for cocaine HCl IP, cocaine HCl PO, and whole Erythroxylum coca extract PO. The ED50's for cocaine HCl in drug naive rats were 19.6 mg/kg (IP) and 34.6 mg/kg (PO). When the dose of E. coca extract was expressed in terms of cocaine HCl content, the ED50 was 52.6 mg/kg (PO). When dose response curves were determined in rats that had received cocaine (45 mg/kg, PO) for 30 days, a shift to the right in the cocaine HCl curve (an ED50 of 98.4 mg/kg PO) indicated tolerance. However, the shift to the right was less for E. coca extract than for cocaine HCl. Although the anorexic activity of E. coca extract was less than that of an equivalent amount of cocaine in naive rats it was often more than that of equivalent doses of cocaine HCl in tolerant rats. Interaction with other constituents of E. coca extract appears to alter the potency of the cocaine content of the extract in different directions in naive and tolerant rats.

  13. Dopamine transporter inhibition is required for cocaine-induced stereotypy

    OpenAIRE

    Tilley, Michael R.; Gu, Howard H.

    2008-01-01

    The primary mechanism by which cocaine induces stereotypy has been difficult to discern because cocaine has three high affinity targets, the reuptake transporters for dopamine (DAT), norepinephrine, and serotonin. To dissect out the role of DAT in cocaine effects, we generated a knock-in mouse line with a cocaine insensitive DAT (DAT-CI mice). DAT-CI mice provide a powerful tool that can directly test whether DAT inhibition is important for cocaine-induced stereotypy. We found that acute coca...

  14. Prenatal screening and genetics

    NARCIS (Netherlands)

    Alderson, P.; Aro, A.R.; Dragonas, T.; Ettorre, E.; Hemminki, E.; Jalinoja, P.; Santalahti, P.; Tijmstra, T.

    Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we

  15. Prenatal stress in pigs

    NARCIS (Netherlands)

    Kranendonk, Godelieve

    2006-01-01

    Studies in many species, including humans, have demonstrated that stress during gestation can have long-term developmental, neuroendocrine, and behavioural effects on the offspring. Because pregnant sows can be subjected to regular stressful situations, it is relevant to study whether prenatal stres

  16. Prenatal screening and genetics

    NARCIS (Netherlands)

    Alderson, P.; Aro, A.R.; Dragonas, T.; Ettorre, E.; Hemminki, E.; Jalinoja, P.; Santalahti, P.; Tijmstra, T.

    2001-01-01

    Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we exami

  17. Prenatal stress in pigs

    NARCIS (Netherlands)

    Kranendonk, Godelieve

    2006-01-01

    Studies in many species, including humans, have demonstrated that stress during gestation can have long-term developmental, neuroendocrine, and behavioural effects on the offspring. Because pregnant sows can be subjected to regular stressful situations, it is relevant to study whether prenatal stres

  18. Prenatal screening and genetics

    DEFF Research Database (Denmark)

    Alderson, P; Aro, A R; Dragonas, T

    2001-01-01

    Although the term 'genetic screening' has been used for decades, this paper discusses how, in its most precise meaning, genetic screening has not yet been widely introduced. 'Prenatal screening' is often confused with 'genetic screening'. As we show, these terms have different meanings, and we ex...

  19. The role of endocannabinoid transmission in cocaine addiction.

    Science.gov (United States)

    Arnold, Jonathon C

    2005-06-01

    Research is beginning to outline a role for the endocannabinoid system in cocaine addiction. Human and animal studies indicate that exogenous cannabinoids modulate the acute rewarding effects of cocaine. These studies, however, cannot directly investigate the necessity of endocannabinoid transmission in cocaine addiction. Studies that do offer a direct assessment show that neither pharmacological antagonism nor deletion of the CB1 receptor alters the acute rewarding effects of cocaine. In contrast, CB1 receptors appear to be involved in the association of cocaine reward with environmental cues and reinstatement of cocaine self-administration. Together, these results point to CB1 receptor antagonists as potential anti-craving compounds in the treatment of cocaine addiction. Given the limitations of human population studies, animal research may be useful in discerning causal inferences between cannabis and cocaine use. While animal research suggests cannabis use may precipitate cocaine relapse, cross-sensitization between cannabinoids and cocaine has not been demonstrated and CB1 receptors do not mediate behavioral sensitization to cocaine. The effect of acute or chronic cocaine on endocannabinoid transmission in reward-related areas of the brain is relatively under-researched. Acute cocaine administration increases anandamide levels in the striatum, an effect that is mediated by dopamine D2-like receptors. Conversely, chronic cocaine exposure has no effect on anandamide, but decreases 2-arachidonylglycerol levels in the limbic forebrain. This review highlights research indicating that the endocannabinoid system may subserve certain aspects of cocaine addiction and suggests avenues for future investigation.

  20. Prenatal programming of neuroendocrine reproductive function.

    Science.gov (United States)

    Evans, Neil P; Bellingham, Michelle; Robinson, Jane E

    2016-07-01

    It is now well recognized that the gestational environment can have long-lasting effects not only on the life span and health span of an individual but also, through potential epigenetic changes, on future generations. This article reviews the "prenatal programming" of the neuroendocrine systems that regulate reproduction, with a specific focus on the lessons learned using ovine models. The review examines the critical roles played by steroids in normal reproductive development before considering the effects of prenatal exposure to exogenous steroid hormones including androgens and estrogens, the effects of maternal nutrition and stress during gestation, and the effects of exogenous chemicals such as alcohol and environment chemicals. In so doing, it becomes evident that, to maximize fitness, the regulation of reproduction has evolved to be responsive to many different internal and external cues and that the GnRH neurosecretory system expresses a degree of plasticity throughout life. During fetal life, however, the system is particularly sensitive to change and at this time, the GnRH neurosecretory system can be "shaped" both to achieve normal sexually differentiated function but also in ways that may adversely affect or even prevent "normal function". The exact mechanisms through which these programmed changes are brought about remain largely uncharacterized but are likely to differ depending on the factor, the timing of exposure to that factor, and the species. It would appear, however, that some afferent systems to the GnRH neurons such as kisspeptin, may be critical in this regard as it would appear to be sensitive to a wide variety of factors that can program reproductive function. Finally, it has been noted that the prenatal programming of neuroendocrine reproductive function can be associated with epigenetic changes, which would suggest that in addition to direct effects on the exposed offspring, prenatal programming could have transgenerational effects on

  1. Child Behavior Problems: Role of Cocaine Use, Parenting and Child Exposure to Violence.

    Science.gov (United States)

    Veira, Yvette; Finger, Brent; Eiden, Rina D; Colder, Craig R

    2014-07-01

    Studies examining the association between prenatal cocaine exposure (PCE) and child behavior problems have yielded mixed results, suggesting a need to identify additional mediating and moderating influences. We hypothesized that the relation between PCE and behavior problems at kindergarten would be mediated/moderated by child exposure to violence; and that maternal warmth/sensitivity and harshness would moderate the association between violence exposure and behavior problems. Participants consisted of 216 (116 cocaine-exposed, 100 non-cocaine exposed (NCE) mother-child dyads participating in an ongoing longitudinal study of PCE. Results yielded no direct or mediated/moderated association between PCE and child behavior problems, and no significant interaction effects between PCE and parenting quality. However, higher exposure to violence in kindergarten was significantly associated with higher child behavior problems. This association was moderated by maternal warmth/sensitivity and harshness. High maternal warmth/sensitivity buffered the association between violence exposure and behavior problems while high maternal harshness exacerbated this association. This study highlights the role of violence exposure in the development of behavior problems among high-risk children, and emphasizes the significance of parenting quality in buffering or exacerbating this risk among these children. Implications for prevention include targeting the potential role of maternal warmth/sensitivity as a protective influence among children exposed to violence.

  2. [{sup 11}]Cocaine: PET studies of cocaine pharmacokinetics, dopamine transporter availability and dopamine transporter occupancy

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, Joanna S. E-mail: fowler@bnl.gov; Volkow, Nora D.; Wang, Gene-Jack; Gatley, S. John; Logan, Jean

    2001-07-01

    Cocaine was initially labeled with carbon-11 in order to track the distribution and pharmacokinetics of this powerful stimulant and drug of abuse in the human brain and body. It was soon discovered that [{sup 11}C]cocaine was not only useful for measuring cocaine pharmacokinetics and its relationship to behavior but that it is also a sensitive radiotracer for dopamine transporter (DAT) availability. Measures of DAT availability were facilitated by the development of a graphical analysis method (Logan Plot) for reversible systems which streamlined kinetic analysis. This expanded the applications of [{sup 11}C]cocaine to studies of DAT availability in the human brain and allowed the first comparative measures of the degree of DAT occupancy by cocaine and another stimulant drug methylphenidate. This article will summarize preclinical and clinical research with [{sup 11}C]cocaine.

  3. Quality of life, social functioning, family structure, and treatment history associated with crack cocaine use in youth from the general population.

    Science.gov (United States)

    Narvaez, Joana C M; Pechansky, Flávio; Jansen, Karen; Pinheiro, Ricardo T; Silva, Ricardo A; Kapczinski, Flávio; Magalhães, Pedro V

    2015-01-01

    To assess the relationship between crack cocaine use and dimensions of quality of life and social functioning in young adults. This was a cross-sectional, population-based study involving 1,560 participants in Pelotas, Brazil. Crack cocaine use and abuse were investigated using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) inventory. Outcomes of interest were quality of life, religiosity, and social functioning in terms of education, occupational status, family structure, and medical treatment history. Lifetime crack cocaine use was associated with poor quality of life, worse functioning, impaired academic performance, and lower religious involvement. A greater maternal presence and higher paternal absence were more also more pronounced in crack cocaine users, who were also more likely to seek psychological and psychiatric treatment than the general population. Quality of life was severely impacted by crack cocaine use, especially in terms of general and physical health. Social functioning also differed between the general population and crack users, who had lower educational attainment and religious involvement. Maternal presence, paternal absence, and mental health-seeking behaviors were also more frequent among crack cocaine users, although these individuals reported lower rates of treatment satisfaction. Crack cocaine users also had significant social impairment, so that interventions involving family management and a greater focus on general health, quality of life, and functioning may make crucial contributions to the recovery of this group.

  4. Quality of life, social functioning, family structure, and treatment history associated with crack cocaine use in youth from the general population

    Directory of Open Access Journals (Sweden)

    Joana C.M. Narvaez

    2015-09-01

    Full Text Available Objective:To assess the relationship between crack cocaine use and dimensions of quality of life and social functioning in young adults.Methods:This was a cross-sectional, population-based study involving 1,560 participants in Pelotas, Brazil. Crack cocaine use and abuse were investigated using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST inventory. Outcomes of interest were quality of life, religiosity, and social functioning in terms of education, occupational status, family structure, and medical treatment history.Results:Lifetime crack cocaine use was associated with poor quality of life, worse functioning, impaired academic performance, and lower religious involvement. A greater maternal presence and higher paternal absence were more also more pronounced in crack cocaine users, who were also more likely to seek psychological and psychiatric treatment than the general population.Conclusion:Quality of life was severely impacted by crack cocaine use, especially in terms of general and physical health. Social functioning also differed between the general population and crack users, who had lower educational attainment and religious involvement. Maternal presence, paternal absence, and mental health-seeking behaviors were also more frequent among crack cocaine users, although these individuals reported lower rates of treatment satisfaction. Crack cocaine users also had significant social impairment, so that interventions involving family management and a greater focus on general health, quality of life, and functioning may make crucial contributions to the recovery of this group.

  5. Cocaine-associated lower limb ischemia.

    LENUS (Irish Health Repository)

    Collins, Chris G

    2011-07-25

    Cocaine-associated thrombosis has been reported in the literature with reports of vascular injuries to cardiac, pulmonary, intestinal, placental, and musculoskeletal vessels; however, injury of the pedal vessels is rare. We report on a 31-year-old man who presented 2 months following a cocaine binge with limb-threatening ischemia without an otherwise identifiable embolic source. Angiography confirmed extensive occlusive disease of the tibioperoneal vessels. The patient improved following therapy with heparin and a prostacyclin analogue. Cocaine-induced thrombosis should be considered in patients presenting with acute arterial insufficiency in the lower limb without any other identifiable cause.

  6. Mitochondrial complex I dysfunction induced by cocaine and cocaine plus morphine in brain and liver mitochondria.

    Science.gov (United States)

    Cunha-Oliveira, Teresa; Silva, Lisbeth; Silva, Ana Maria; Moreno, António J; Oliveira, Catarina R; Santos, Maria S

    2013-06-07

    Mitochondrial function and energy metabolism are affected in brains of human cocaine abusers. Cocaine is known to induce mitochondrial dysfunction in cardiac and hepatic tissues, but its effects on brain bioenergetics are less documented. Furthermore, the combination of cocaine and opioids (speedball) was also shown to induce mitochondrial dysfunction. In this work, we compared the effects of cocaine and/or morphine on the bioenergetics of isolated brain and liver mitochondria, to understand their specific effects in each tissue. Upon energization with complex I substrates, cocaine decreased state-3 respiration in brain (but not in liver) mitochondria and decreased uncoupled respiration and mitochondrial potential in both tissues, through a direct effect on complex I. Morphine presented only slight effects on brain and liver mitochondria, and the combination cocaine+morphine had similar effects to cocaine alone, except for a greater decrease in state-3 respiration. Brain and liver mitochondrial respirations were differentially affected, and liver mitochondria were more prone to proton leak caused by the drugs or their combination. This was possibly related with a different dependence on complex I in mitochondrial populations from these tissues. In summary, cocaine and cocaine+morphine induce mitochondrial complex I dysfunction in isolated brain and liver mitochondria, with specific effects in each tissue.

  7. Alcohol Alert

    Science.gov (United States)

    ... main content National Institute on Alcohol Abuse and Alcoholism (NIAAA) Main Menu Search Search form Search Alcohol & ... on a single aspect of alcohol abuse and alcoholism. Please click on the desired publication for full ...

  8. [Ten years of emergency attendances for cocaine-users in Spain].

    Science.gov (United States)

    Galicia, Miguel; Nogué, Santiago; Burillo-Putze, Guillermo

    2014-10-07

    Cocaine is the second most consumed illegal drug in the western world, following cannabis. Since 1998, it is also the drug that more attendances generate in different emergency devices, and it is responsible for more of 60% of the emergencies directly related to drug consumption. This work reviews the main Spanish scientific articles published in the last 10 years, in which different factors related to the use of this drug have been analyzed in relation to the use of emergency by cocaine users. A total of 8,795 patients were included (interval 57-1,755), with an average age of 32.64 years (SD 3.02), and an average percentage of positives to cocaine of 54.78% (SD 47.03); there were 7 works with 100% of subjects being positive to cocaine. Males predominated with an average of 78.69% (SD 12). They presented cardiovascular symptoms in 30% cases (SD 22.7), neurological symptoms in 11.6% cases (SD 4.28) and psychiatric symptoms in 49.32% cases (SD 23.87). There was a multiple consumption in 49.02% of patients (interval 4.3-76.2), fundamentally associated with alcohol (57.78%, SD 6.18) and cannabis (21.56%, SD 10.72). Two hundred and forty-six patients (2.8%) needed admission and 8 died (0.09%). Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Levamisole-contaminated cocaine: a hairy affair.

    Science.gov (United States)

    van der Veer, Tjeerd; Pennings, Ed; Tervaert, J W Cohen; Korswagen, Lindy-Anne

    2015-08-26

    Levamisole-contaminated cocaine can induce severe systemic vasculitis. The diagnosis can be challenging, especially when substance abuse is uncertain. We present the case of a 42-year-old woman suffering from vasculitis due to levamisole-contaminated cocaine, who persistently denied substance abuse. Symptoms included ulcerating skin lesions, arthralgia and myalgia, and the occurrence of an ileal intussusception. The definitive diagnosis was made using hair testing for toxins. She recovered through cocaine abstinence, but re-exposure resulted in a severe relapse with glomerulonephritis. Importantly, at time of the relapse, the patient became positive for both myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA) and proteinase 3-ANCA. Cocaine-levamisole-induced vasculitis poses a great clinical challenge. The proper diagnostic strategy and therapy is still controversial. We highlight our diagnostic and therapeutic considerations, including hair testing for definitive proof of exposure.

  11. Stimulus control of cocaine self-administration

    National Research Council Canada - National Science Library

    Weiss, Stanley J; Kearns, David N; Cohn, Scott I; Schindler, Charles W; Panlilio, Leigh V

    2003-01-01

    .... Stimulus control of cocaine self-administration was generated here for the first time using multiple and chained schedules with short, frequently-alternating components--like those typically used...

  12. Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers.

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Tomasi, D.; Telang, F.; Fowler, J.S.; Pradhan, K.; Jayne, M.; Logan, J.; Goldstein, R.Z.; Alia-Klein, N.; Wong, C.T.

    2010-07-01

    Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and {sup 18}FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue

  13. Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats

    Science.gov (United States)

    Eagle, Andrew L.; Singh, Robby; Kohler, Robert J.; Friedman, Amy L.; Liebowitz, Chelsea P.; Galloway, Matthew P.; Enman, Nicole M.; Jutkiewicz, Emily M.; Perrine, Shane A.

    2017-01-01

    Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague–Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0,10 or 20mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, asexpected. However, compared to control ratson Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement. PMID:25712697

  14. Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers.

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    Full Text Available Dopamine (phasic release is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function was measured with PET and (18FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg. The Cocaine-cues video increased craving to the same extent with placebo (68% and with methylphenidate (64%. In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005 in left limbic regions (insula, orbitofrontal, accumbens and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005, amygdala, striatum and middle insula (p<0.05. This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes, which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic

  15. Human prenatal diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Filkins, K.; Russo, R.J.

    1985-01-01

    The multiauthor text is written as a ''guide to rationalize and clarify certain aspects of diagnosis, general counseling and intervention'' for ''health professionals who provide care to pregnant women.'' The text is not aimed at the ultrasonographer but rather at the physicians who are clinically responsible for patient management. Chapters of relevance to radiologists include an overview of prenatal screening and counseling, diagnosis of neural tube defects, ultrasonographic (US) scanning of fetal disorders in the first and second trimesters of pregnancy, US scanning in the third trimester, multiple gestation and selective termination, fetal echo and Doppler studies, and fetal therapy. Also included are overviews of virtually all currently utilized prenatal diagnostic techniques including amniocentesis, fetal blood sampling, fetoscopy, recombinant DNA detection of hemoglobinopathies, chorionic villus sampling, embryoscopy, legal issues, and diagnosis of Mendelian disorders by DNA analysis.

  16. The inhibition of cocaine-induced locomotor activity by CART 55-102 is lost after repeated cocaine administration.

    Science.gov (United States)

    Job, Martin O; Shen, Li L; Kuhar, Michael J

    2013-08-29

    CART peptide is known for having an inhibitory effect on cocaine- and dopamine-mediated actions after acute administration of cocaine and dopamine. In this regard, it is postulated to be a homeostatic, regulatory factor on dopaminergic activity in the nucleus accumbens (NAc). However, there is no data on the effect of CART peptide after chronic administration of cocaine, and this study addresses this. It was found that CART peptide blunted cocaine-induced locomotion (LMA) after acute administration of cocaine, as expected, but it did not affect cocaine-mediated LMA after chronic administration of cocaine. The loss of CART peptide's inhibitory effect did not return for up to 9 weeks after stopping the repeated cocaine administration. It may not be surprising that homeostatic regulatory mechanisms in the NAc are lost after repeated cocaine administration, and that this may be a mechanism in the development of addiction.

  17. Immunopharmacotherapeutic manifolds and modulation of cocaine overdose.

    Science.gov (United States)

    Treweek, Jennifer B; Roberts, Amanda J; Janda, Kim D

    2011-05-01

    Cocaine achieves its psychostimulant, reinforcing properties through selectively blocking dopamine transporters, and this neurobiological mechanism impedes the use of classical receptor-antagonist pharmacotherapies to outcompete cocaine at CNS sites. Passive immunization with monoclonal antibodies (mAb) specific for cocaine circumvents this problem as drug is sequestered in the periphery prior to entry into the brain. To optimize an immunopharmacotherapeutic strategy for reversing severe cocaine toxicity, the therapeutic properties of mAb GNC92H2 IgG were compared to those of its engineered formats in a mouse overdose model. Whereas the extended half-life of an IgG justifies its application to the prophylactic treatment of addiction, the rapid, thorough biodistribution of mAb-based fragments, including F(ab')₂, Fab and scFv, may correlate to accelerated scavenging of cocaine and reversal of toxicity. To test this hypothesis, mice were administered the anti-cocaine IgG (180 mg/kg, i.v.) or GNC92H2-based agent after receiving an LD₅₀ cocaine dose (93 mg/kg, i.p.), and the timeline of overdose symptoms was recorded. All formats lowered the rate of lethality despite the >100-fold molar excess of drug to antibody binding capacity. However, only F(ab')₂-92H2 and Fab-92 H2 significantly attenuated the progression of premorbid behaviors, and Fab-92H2 prevented seizure generation in a percentage of mice. The calculation of serum half-life of each format demonstrated that the pharmacokinetic profile of Fab-92H2 (elimination half-life, t½~100 min) best approximated that of cocaine. These results not only confirm the importance of highly specific and tight drug binding by the mAb, but also highlight the benefit of aligning the pharmacokinetic and pharmacodynamic properties of the immunopharmacotherapeutic with the targeted drug. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Prenatal testosterone and stuttering.

    Science.gov (United States)

    Montag, Christian; Bleek, Benjamin; Breuer, Svenja; Prüss, Holger; Richardt, Kirsten; Cook, Susanne; Yaruss, J Scott; Reuter, Martin

    2015-01-01

    The prevalence of stuttering is much higher in males compared to females. The biological underpinnings of this skewed sex-ratio is poorly understood, but it has often been speculated that sex hormones could play an important role. The present study investigated a potential link between prenatal testosterone and stuttering. Here, an indirect indicator of prenatal testosterone levels, the Digit Ratio (2D:4D) of the hand, was used. As numerous studies have shown, hands with more "male" characteristics (putatively representing greater prenatal testosterone levels) are characterized by a longer ring finger compared to the index finger (represented as a lower 2D:4D ratio) in the general population. We searched for differences in the 2D:4D ratios between 38 persons who stutter and 36 persons who do not stutter. In a second step, we investigated potential links between the 2D:4D ratio and the multifaceted symptomatology of stuttering, as measured by the Overall Assessment of the Speaker's Experience of Stuttering (OASES), in a larger sample of 44 adults who stutter. In the first step, no significant differences in the 2D:4D were observed between individuals who stutter and individuals who do not stutter. In the second step, 2D:4D correlated negatively with higher scores of the OASES (representing higher negative experiences due to stuttering), and this effect was more pronounced for female persons who stutter. The findings indicate for the first time that prenatal testosterone may influence individual differences in psychosocial impact of this speech disorder. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Evaluation of buspirone for relapse-prevention in adults with cocaine dependence: an efficacy trial conducted in the real world.

    Science.gov (United States)

    Winhusen, Theresa; Brady, Kathleen T; Stitzer, Maxine; Woody, George; Lindblad, Robert; Kropp, Frankie; Brigham, Gregory; Liu, David; Sparenborg, Steven; Sharma, Gaurav; Vanveldhuisen, Paul; Adinoff, Bryon; Somoza, Eugene

    2012-09-01

    Cocaine dependence is a significant public health problem for which there are currently no FDA-approved medications. Hence, identifying candidate compounds and employing an efficient evaluation process is crucial. This paper describes key design decisions made for a National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) study that uses a novel two-stage process to evaluate buspirone (60 mg/day) for cocaine-relapse prevention. The study includes pilot (N=60) and full-scale (estimated N=264) trials. Both trials will be randomized, double-blind, and placebo-controlled and both will enroll treatment-seeking cocaine-dependent participants engaged in inpatient/residential treatment and scheduled for outpatient treatment post-discharge. All participants will receive contingency management in which incentives are given for medication adherence as evaluated by the Medication Events Monitoring System (MEMS). The primary outcome measure is maximum days of continuous cocaine abstinence, as assessed by twice-weekly urine drug screens (UDS) and self-report, during the 15-week outpatient treatment phase. Drug-abuse outcomes include cocaine use as assessed by UDS and self-report of cocaine use, other substance use as assessed by UDS and self-report of substance use (i.e., alcohol and/or illicit drugs), cocaine bingeing, HIV risk behavior, quality of life, functioning, and substance abuse treatment attendance. Unique aspects of the study include conducting an efficacy trial in community treatment programs, a two-stage process to efficiently evaluate buspirone, and an evaluation of mediators by which buspirone might exert a beneficial effect on relapse prevention.

  20. Socio-demographic and clinical characteristics of pregnant and puerperal crack-cocaine using women: preliminary data

    Directory of Open Access Journals (Sweden)

    MARIA LUCRÉCIA SCHERER ZAVASCHI

    2014-01-01

    Full Text Available Background The literature provides several studies on the effects of cocaine when exposed to the fetus. However, the majority of these data comes from animal models. Objective The objective of this study is to present socio-demographic and clinical data in crack-cocaine using pregnant women and their babies, as compared to non-users. Methods Cross-sectional study, comprised by 56 dyads of crack-cocaine using mothers-babies and 89 control dyads. In addition to the socio-demographic data and the babies’ information, data collection was based on ABIPEMI for socioeconomic level, WAIS for IQ, MINI for psychopathology and ASSIST for drug use. Results Most crack users, in comparison to non-users, did not have a partner (10.52% vs 4.4%, P = 0.001 and presented lower IQ (78.15, +/-8.07 vs 84.27 +/- 9.87; P = 0.002. The prevalence of antisocial personality disorder and suicide risk in users was higher than in non-users (24.44% vs none, P < 0.001; 28.26% vs 10.46% P = 0.01. Most of the users did not participate in prenatal care (75%. The babies that the crack-cocaine using mothers gave birth to weighed significantly less than the controls (2.858 g vs 3.240 g, P = 0.002. Discussion Users had a higher degree of psychopathology and lower attendance in prenatal care. There was an overlap of adverse factors, both for exposed mothers and babies. The sum of these vulnerabilities could result in significant harm to the developing infant.

  1. Vaccines against stimulants: cocaine and MA.

    Science.gov (United States)

    Kosten, Thomas; Domingo, Coreen; Orson, Frank; Kinsey, Berma

    2014-02-01

    While the worldwide prevalence of cocaine use remains significant, medications, or small molecule approaches, to treat drug addictions have met with limited success. Anti-addiction vaccines, on the other hand, have demonstrated great potential for treating drug abuse using a distinctly different mechanism of eliciting an antibody response that blocks the pharmacological effects of drugs. We provide a review of vaccine-based approaches to treating stimulant addictions; specifically and cocaine addictions. This selective review article focuses on the one cocaine vaccine that has been into clinical trials and presents new data related to pre-clinical development of a methamphetamine (MA) vaccine. We also review the mechanism of action for vaccine induced antibodies to abused drugs, which involves kinetic slowing of brain entry as well as simple blocking properties. We present pre-clinical innovations for MA vaccines including hapten design, linkage to carrier proteins and new adjuvants beyond alum. We provide some new information on hapten structures and linkers and variations in protein carriers. We consider a carrier, outer membrance polysaccharide coat protein (OMPC), that provides some self-adjuvant through lipopolysaccharide components and provide new results with a monophosopholipid adjuvant for the more standard carrier proteins with cocaine and MA. The review then covers the clinical trials with the cocaine vaccine TA-CD. The clinical prospects for advances in this field over the next few years include a multi-site cocaine vaccine clinical trial to be reported in 2013 and phase 1 clinical trials of a MA vaccine in 2014.

  2. Smoked cocaine in socially-depressed areas

    Directory of Open Access Journals (Sweden)

    Díaz Olga

    2010-11-01

    Full Text Available Abstract Background The main objectives of this study are to describe the smoked cocaine user's profile in socially-depressed areas and their needs from a harm-reduction perspective, to investigate their use of smoking crack and compare the acute effects between injecting and smoking consumption. Methods The study took place in SAPS, Barcelona, Spain. Two focus group sessions were undertaken with a total of 8 drug users. Secondly, the 8 participants answered a structured questionnaire and in the course of the sessions, as a snowball activity, were trained to survey 6 other crack smokers. Results We obtained 56 questionnaires. The majority of participants were from non-European Community countries (62.69%, 70.2% of participants referred to sharing the smoking equipment. The most frequent symptoms reported during smoked cocaine were mydriasis (83.33%, perspiration (72.92% and compulsive object search (70.83% During the group sessions, participants said that smoked cocaine is much more addictive than injected cocaine and causes more anxiety. Participants also reported the difficulty of changing from injected use to smoked use, due to the larger amount of cocaine needed to reach the same effects as when having injected. Conclusions We can conclude that the research, focused on achieving greater knowledge of the smoked cocaine user's profile, their usage of smoking crack, consumption patterns and acute effects, should be incorporated into substance misuse interventions.

  3. Molecular mechanisms mediating a deficit in recall of fear extinction in adult mice exposed to cocaine in utero.

    Directory of Open Access Journals (Sweden)

    Zeeba D Kabir

    Full Text Available Prenatal cocaine exposure has been shown to alter cognitive processes of exposed individuals, presumed to be a result of long-lasting molecular alterations in the brain. In adult prenatal cocaine exposed (PCOC mice we have identified a deficit in recall of fear extinction, a behavior that is dependent on the medial prefrontal cortex (mPFC and the hippocampus. While we observed no change in the constitutive expression of brain derived neurotrophic factor (BDNF protein and mRNA in the mPFC and hippocampus of adult PCOC mice, we observed blunted BDNF signaling in the mPFC of adult PCOC mice after fear extinction compared to the control animals. Specifically, during the consolidation phase of the extinction memory, we observed a decrease in BDNF protein and it's phospho-TrkB receptor expression. Interestingly, at this same time point there was a significant increase in total Bdnf mRNA levels in the mPFC of PCOC mice as compared with controls. In the Bdnf gene, we identified decreased constitutive binding of the transcription factors, MeCP2 and P-CREB at the promoters of Bdnf exons I and IV in the mPFC of PCOC mice, that unlike control mice remained unchanged when measured during the behavior. Finally, bilateral infusion of recombinant BDNF protein into the infralimbic subdivision of the mPFC during the consolidation phase of the extinction memory rescued the behavioral deficit in PCOC mice. In conclusion, these findings extend our knowledge of the neurobiologic impact of prenatal cocaine exposure on the mPFC of mice, which may lead to improved clinical recognition and treatment of exposed individuals.

  4. Congenital dacryocystocele: prenatal MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Yazici, Zeynep [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Uludag University, Department of Radiology, Faculty of Medicine, Bursa (Turkey); Kline-Fath, Beth M.; Rubio, Eva I.; Calvo-Garcia, Maria A.; Linam, Leann E. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Yazici, Bulent [Uludag University, Department of Ophthalmology, Faculty of Medicine, Bursa (Turkey)

    2010-12-15

    Congenital dacryocystocele can be diagnosed prenatally by imaging. Prenatal MRI is increasingly utilized for fetal diagnosis. To present the radiological and clinical features of seven fetuses with congenital dacryocystocele diagnosed with prenatal MRI. The institutional database of 1,028 consecutive prenatal MR examinations performed during a period of 4 years was reviewed retrospectively. The cases of congenital dacryocystocele were identified by reading the report of each MRI study. The incidence of dacryocystocele diagnosed with prenatal MRI was 0.7% (n=7/1,028). The dacryocystocele was bilateral in three fetuses. Mean gestational age at the time of diagnosis was 31 weeks. The indication for prenatal MRI was the presence or the suspicion of central nervous system abnormality in six fetuses and diaphragmatic hernia in one. Dacryocystocele was associated with an intranasal cyst in six of ten eyes. Prenatal sonography revealed dacryocystocele in only two of seven fetuses. Of eight eyes with postnatal follow-up, four did not have any lacrimal symptoms. Prenatal MRI can delineate congenital dacryocystocele more clearly and in a more detailed fashion than ultrasonography. Presence of dacryocystocele was symptomatic in only 50% of our patients, supporting that prenatal diagnosis of dacryocystocele might follow a benign course. (orig.)

  5. Cocaine

    Science.gov (United States)

    ... Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the ... Health Effects Statistics and Trends Swipe left or right to scroll. Monitoring the Future Study: Trends in ...

  6. Cocaine

    Science.gov (United States)

    ... something they enjoy, like eating a piece of chocolate cake or playing a video game. Normally, dopamine ... 03, 2016 The 2015 Monitoring the Future College Students and Adults survey shows trends in the use ...

  7. Levamisole-adulterated cocaine: Two fatal case reports and evaluation of possible cocaine toxicity potentiation.

    Science.gov (United States)

    Indorato, Francesca; Romano, Guido; Barbera, Nunziata

    2016-08-01

    Levamisole has been identified as a cocaine adulterant in the United States since 2002. Although there is a variation in the percentage of levamisole in cocaine samples between European countries, measurement of levamisole in human samples of cocaine users has become increasingly important. To our best knowledge, only five deaths are reported (one twice) as a result of complications secondary to levamisole-tainted cocaine and none of these cases reports the post-mortem levamisole concentration. In this article, we present the post-mortem levamisole concentrations in fluids and tissues in two young cocaine users, dead after levamisole-adulterated cocaine intake. With the dearth of levamisole reported concentrations in literature, this particular report is of interest to the forensic toxicological and pathological communities. This article aims to be a supplementary alert to aware the risk that may occur using levamisole-adulterated cocaine and an incentive to publication of toxicity reports and new researches involving the combination of levamisole and cocaine.

  8. Social Support among Late Adolescent Users of Alcohol and Other Drugs.

    Science.gov (United States)

    Christmon, Kenneth

    1994-01-01

    Analysis of data on 1,121 older adolescents and young adults from a national longitudinal survey examined effects of community involvement, social satisfaction, social network size, race, gender, and age on use of alcohol, marijuana, and cocaine. Social support did influence use of alcohol and other drugs, but the direction of influence varied by…

  9. Behaviors, Attitudes and Knowledge of UNO Students Regarding Drugs, Alcohol and Tobacco: 1989.

    Science.gov (United States)

    Hunnicutt, David; Davis, Joe

    1989-01-01

    This report describes alcohol, tobacco, and other drug use among 715 University of Nebraska at Omaha (UNO) students. The report focuses on drug use at the higher frequency levels, rather than reporting proportions who have ever used various drugs. The separate classes of drugs distinguished are alcohol, tobacco, cocaine, marijuana, and…

  10. Behavioral momentum of cocaine self-administration: effects of frequency of reinforcement on resistance to extinction.

    Science.gov (United States)

    Quick, Stacey L; Shahan, Timothy A

    2009-07-01

    Persistent drug seeking is a defining property of substance abuse and is generally thought to depend, in part, on exposure to drug-associated contexts. Behavioral momentum theory provides a set of methods and a theoretical framework for understanding how stimulus contexts contribute to the persistence of operant behavior. Earlier research has extended behavioral momentum theory to alcohol self-administration, but not to intravenous drug self-administration. This experiment extended behavioral momentum theory to cocaine self-administration by examining the effects of frequency of cocaine reinforcement in a context on resistance to extinction. Rats self-administered 0.32 mg/kg infusions of cocaine in a multiple schedule of reinforcement arranging two distinct contexts. Responding in a Rich context was reinforced by cocaine infusions at a higher frequency (i.e. variable interval 120 s) and in a Lean context at a lower frequency (variable interval 360 s). After establishment of responding in the two contexts, resistance to extinction was examined. Preextinction response rates for cocaine were similar in the Rich and Lean contexts. Nonetheless, relative resistance to extinction was greater in the Rich context than in the Lean context. The difference in resistance to extinction in the two contexts was well described by a quantitative model of behavioral momentum. These results suggest that the frequency of drug reinforcement in a context contributes to the persistence of drug seeking in that context, and that behavioral momentum theory might be useful for understanding how drug-associated contexts contribute to the persistence of drug seeking.

  11. The fast and furious : Cocaine, amphetamines and harm reduction

    NARCIS (Netherlands)

    J-P.C. Grund (Jean-Paul); P. Coffin (Philip); M. Jauffret-Roustide (Marie); M. Dijkstra (Minke); D. de Bruin (Dick); P. Blanken (Peter)

    2010-01-01

    textabstractCocaine and amphetamines (‘stimulants’) are distinct central nervous system stimulants with similar effects (Pleuvry, 2009; Holman, 1994). Cocaine is a crystalline tropane alkaloid extracted from coca leaves. Amphetamines are a subclass of phenylethylamines with primarily stimulant

  12. D-cycloserine and cocaine cue reactivity: preliminary findings.

    Science.gov (United States)

    Price, Kimber L; McRae-Clark, Aimee L; Saladin, Michael E; Maria, Megan M Moran-Santa; DeSantis, Stacia M; Back, Sudie E; Brady, Kathleen T

    2009-01-01

    D-cycloserine (DCS), a partial glutamate N-methyl-D-aspartic acid (NMDA) receptor agonist, enhances extinction of conditioned fear responding in rodents and facilitates exposure-based learning in humans with anxiety disorders. This preliminary study investigates DCS pretreatment on response to cocaine cues in cocaine-dependent subjects. Ten cocaine-dependent subjects were randomly assigned to receive either 50 mg DCS or matching placebo two hours before each of two 1-hour cocaine cue exposure sessions one day apart. HR and craving ratings were obtained before and during cue exposure sessions. There was a trend towards increased craving to cocaine cues in cocaine-dependent individuals after administration of DCS. The administration of DCS prior to cue exposure sessions may facilitate response activation. While facilitation of extinction-based learning by DCS may have therapeutic potential for cocaine dependence, this drug may exhibit a different profile in cocaine-dependent individuals as compared to those with anxiety disorders.

  13. Behavioral Screening for Cocaine Sensitivity in Mutagenized Zebrafish

    National Research Council Canada - National Science Library

    Tristan Darland; John E. Dowling

    2001-01-01

    .... Here, we report that zebrafish exhibit cocaine-induced conditioned place preference. In a pilot screen of 18 F generation families of mutagenized fish, we found three with abnormally low responses to cocaine...

  14. The long-term effects of prenatal nicotine exposure on response inhibition: an fMRI study of young adults.

    Science.gov (United States)

    Longo, Carmelinda A; Fried, Peter A; Cameron, Ian; Smith, Andra M

    2013-01-01

    The long-term effects of prenatal nicotine exposure on response inhibition were investigated in young adults using functional magnetic resonance imaging (fMRI). Participants were members of the Ottawa Prenatal Prospective Study, a longitudinal study that collected a unique body of information on participants from infancy to young adulthood, which allowed for the measurement of an unprecedented number of potentially confounding drug exposure variables including: prenatal marijuana and alcohol exposure and current marijuana, nicotine and alcohol use. Twelve young adults with prenatal nicotine exposure and 13 non-exposed controls performed a Go/No-Go task while fMRI blood oxygen level-dependent responses were examined. Despite similar task performance, participants prenatally exposed to nicotine demonstrated significantly greater activity in several regions of the brain that typically subserve response inhibition including the inferior frontal gyrus, the inferior parietal lobe, the thalamus and the basal ganglia. In addition, prenatally exposed participants showed greater activity in relatively large posterior regions of the cerebellum. These results suggest that prenatal nicotine exposure leads to altered neural functioning during response inhibition that continues into adulthood. This alteration is compensated for by recruitment of greater neural resources within regions of the brain that subserve response inhibition and the recruitment of additional brain regions to successfully perform the task. Response inhibition is an important executive functioning skill and impairments can impede functioning in much of everyday life. Thus, awareness of the continued long-term neural physiological effects of prenatal nicotine exposure is critical.

  15. The place of prenatal clases.

    Science.gov (United States)

    Enkin, M W

    1978-11-01

    The past 20 years has shown an exponential rise in both obstetrical intervention and family centred maternity care. Prenatal classes, although not as yet fully integrated into prenatal care, fill a vital role in teaching couples the information, skills, and attitudes required to participate actively in their reproductive care, and to recognize both their rights and their responsibilities.

  16. Alcohol Intolerance

    Science.gov (United States)

    ... beer-alcohol.aspx. Accessed Jan. 16, 2015. Alcohol angioedema and uticaria. American Academy of Allergy, Asthma & Immunology. http://www.aaaai.org/ask-the-expert/alcohol-angioedema-urticaria.aspx. Accessed Jan. 16, 2015. Alcohol and ...

  17. Pharmacologic approaches to the treatment of cocaine dependence.

    OpenAIRE

    Taylor, W. A.; Gold, M. S.

    1990-01-01

    When pharmacologic agents are considered in the treatment of cocaine addiction, the objective of such treatment--sustained abstinence--must be considered. Medication and medical approaches have been disappointing in the treatment of cocaine overdose. The central neurobiologic mechanism(s) involved in cocaine toxicity are poorly understood. Without a cocaine antagonist, pharmacologic approaches have been less than promising in preventing relapse. Various psychoactive medications have been trie...

  18. Cocaine use severity and cerebellar gray matter are associated with reversal learning deficits in cocaine-dependent individuals

    NARCIS (Netherlands)

    Moreno-López, L.; Perales, J.C.; van Son, D.; Albein-Urios, N.; Soriano-Mas, C.; Martinez-Gonzalez, J.M.; Wiers, R.W.; Verdejo-García, A.

    2015-01-01

    Cocaine addiction involves persistent deficits to unlearn previously rewarded response options, potentially due to neuroadaptations in learning-sensitive regions. Cocaine-targeted prefrontal systems have been consistently associated with reinforcement learning and reversal deficits, but more recent

  19. Cocaine use severity and cerebellar gray matter are associated with reversal learning deficits in cocaine-dependent individuals

    NARCIS (Netherlands)

    Moreno-López, L.; Perales, J.C.; van Son, D.; Albein-Urios, N.; Soriano-Mas, C.; Martinez-Gonzalez, J.M.; Wiers, R.W.; Verdejo-García, A.

    2015-01-01

    Cocaine addiction involves persistent deficits to unlearn previously rewarded response options, potentially due to neuroadaptations in learning-sensitive regions. Cocaine-targeted prefrontal systems have been consistently associated with reinforcement learning and reversal deficits, but more recent

  20. Contingent reinforcement of abstinence with individuals abusing cocaine and marijuana.

    OpenAIRE

    Budney, A J; Higgins, S T; Delaney, D D; Kent, L; Bickel, W K

    1991-01-01

    Two males diagnosed with cocaine dependence received a behavioral intervention comprised of contingency management and the community reinforcement approach. During the initial phase of treatment, reinforcement was delivered contingent on submitting cocaine-free urine specimens. The community reinforcement approach involved two behavior therapy sessions each week. Almost complete cocaine abstinence was achieved, but regular marijuana use continued. During a second phase, reinforcement magnitud...

  1. Limited Cutaneous Vasculitis Associated With Levamisole-Adulterated Cocaine

    Science.gov (United States)

    Yachoui, Ralph; Kolasinski, Sharon L; Eid, Hala

    2012-01-01

    Levamisole is among the many contaminants that have been detected in seized cocaine throughout North America and Europe. Little is known about the association between levamisole-adulterated cocaine and vasculitis. Herein we describe a case of limited cutaneous vasculitis manifested as retiform purpura and skin necrosis in a user of cocaine contaminated with levamisole. PMID:23024742

  2. Effects of cocaine on honey bee dance behaviour.

    Science.gov (United States)

    Barron, Andrew B; Maleszka, Ryszard; Helliwell, Paul G; Robinson, Gene E

    2009-01-01

    The role of cocaine as an addictive drug of abuse in human society is hard to reconcile with its ecological role as a natural insecticide and plant-protective compound, preventing herbivory of coca plants (Erythroxylum spp.). This paradox is often explained by proposing a fundamental difference in mammalian and invertebrate responses to cocaine, but here we show effects of cocaine on honey bees (Apis mellifera L.) that parallel human responses. Forager honey bees perform symbolic dances to advertise the location and value of floral resources to their nest mates. Treatment with a low dose of cocaine increased the likelihood and rate of bees dancing after foraging but did not otherwise increase locomotor activity. This is consistent with cocaine causing forager bees to overestimate the value of the floral resources they collected. Further, cessation of chronic cocaine treatment caused a withdrawal-like response. These similarities likely occur because in both insects and mammals the biogenic amine neuromodulator systems disrupted by cocaine perform similar roles as modulators of reward and motor systems. Given these analogous responses to cocaine in insects and mammals, we propose an alternative solution to the paradox of cocaine reinforcement. Ecologically, cocaine is an effective plant defence compound via disruption of herbivore motor control but, because the neurochemical systems targeted by cocaine also modulate reward processing, the reinforcing properties of cocaine occur as a ;side effect'.

  3. Mice lacking neuropeptide Y show increased sensitivity to cocaine

    DEFF Research Database (Denmark)

    Sørensen, Gunnar; Woldbye, David Paul Drucker

    2012-01-01

    There is increasing data implicating neuropeptide Y (NPY) in the neurobiology of addiction. This study explored the possible role of NPY in cocaine-induced behavior using NPY knockout mice. The transgenic mice showed a hypersensitive response to cocaine in three animal models of cocaine addiction...

  4. Individual differences in cocaine addiction: maladaptive behavioural traits

    NARCIS (Netherlands)

    Homberg, J.R.; Karel, P.G.A.; Verheij, M.M.M.

    2014-01-01

    Cocaine use leads to addiction in only a subset of individuals. Understanding the mechanisms underlying these individual differences in the transition from cocaine use to cocaine abuse is important to develop treatment strategies. There is agreement that specific behavioural traits increase the risk

  5. Maybe a new killer in illicit cocaine.

    Science.gov (United States)

    Fucci, Nadia

    2011-06-15

    This is the study of the author that refers about a case of a 46 years old man found dead inside his house, the death was related to cocaine intake. The police found the corpse laying in his bed with a sheet of newspaper rolled up and a few plastic coverings containing trace of cocaine on the desk. Toxicological analysis was performed and drug levels measured by means of gas chromatography/mass spectrometry technology. Based on the autopsy findings and toxicological results the cause of death was related to an acute intoxication due to cocaine "overdose". In addition to the presence of cocaine and smaller alkaloids, in the sheet made of newspaper rolled up and eluted of the nasal mucosas has been highlighted the presence of 2,6-disopropylnaphtalene (2,6-DIPN), a fungicidal pesticide very health hazard for human. A very easy, simple and selective gas chromatography mass spectrometry method was employed for the detection of 2,6-DIPN in the cocaine powder. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Novel pharmacotherapeutic treatments for cocaine addiction

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    Kosten Thomas R

    2011-11-01

    Full Text Available Abstract Cocaine is a stimulant that leads to the rapid accumulation of catecholamines and serotonin in the brain due to prevention of their re-uptake into the neuron that released the neurotransmitter. Cocaine dependence is a public health concern and cause of significant morbidity and mortality worldwide. At present, there are no approved medications for the treatment of this devastating illness, and behavioral interventions have proven to be of limited use. However, there have been a number of recent trials testing promising agents including dopamine agonists, GABAergic medications and the cocaine vaccine. Here we discuss the most recent human clinical trials of potential medications for treatment of cocaine dependence, as well as pre-clinical studies for another promising agent, levo tetrahydropalmatine. Examination of these recent findings shows promise for GABAergic medications and the cocaine vaccine, as well as unique medications such as disulfiram, whose mechanism remains to be determined. Future work may also confirm specific subgroups of patients for treatment response based on clinical characteristics, biomarkers and pharmacogenetics. This review highlights the need for further, bigger studies in order to determine optimal clinical usage.

  7. Susceptibility to traumatic stress sensitizes the dopaminergic response to cocaine and increases motivation for cocaine.

    Science.gov (United States)

    Brodnik, Zachary D; Black, Emily M; Clark, Meagan J; Kornsey, Kristen N; Snyder, Nathaniel W; España, Rodrigo A

    2017-10-01

    Patients with post-traumatic stress disorder have a heightened vulnerability to developing substance use disorders; however, the biological underpinnings of this vulnerability remain unresolved. We used the predator odor stress model of post-traumatic stress disorder with segregation of subjects as susceptible or resilient based on elevated plus maze behavior and context avoidance. We then determined behavioral and neurochemical differences across susceptible, resilient, and control populations using a panel of behavioral and neurochemical assays. Susceptible subjects showed a significant increase in the motoric and dopaminergic effects of cocaine, and this corresponded with heightened motivation to self-administer cocaine. Resilient subjects did not show differences in the motoric effects of cocaine, in dopamine signaling in vivo, or in any measure of cocaine self-administration. Nonetheless, we found that these animals displayed elevations in both the dopamine release-promoting effects of cocaine and dopamine autoreceptor sensitivity ex vivo. Our results suggest that the experience of traumatic stress may produce alterations in dopamine systems that drive elevations in cocaine self-administration behavior in susceptible subjects, but may also produce both active and passive forms of resilience that function to prevent gross changes in cocaine's reinforcing efficacy in resilient subjects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Examination of cocaine dose in a preclinical model of natural reward devaluation by cocaine.

    Science.gov (United States)

    Green, Jennifer L; Dykstra, Linda A; Carelli, Regina M

    2015-06-01

    In a preclinical model of natural reward devaluation by cocaine, taste cues elicit aversive taste reactivity when they predict impending but delayed cocaine self-administration. Here, we investigated this negative affective state as a function of cocaine dose. Male, Sprague-Dawley rats were given 45 brief intraoral infusions of a 0.15% saccharin solution before 2 h cocaine self-administration for 14 days. Rats were video recorded; taste reactivity and patterns of self-administration were quantified on the first and last days. On day 14, a significant decrease in appetitive taste reactivity and increase in aversive taste reactivity was observed (compared with day 1) that did not vary as a function of cocaine dose. In contrast, patterns of cocaine self-administration (i.e. the total number of lever presses and load-up behavior) varied as a function of dose across days. Further, load-up behavior was positively correlated with aversive taste reactivity (i.e. gapes) on day 14 across all doses tested. Collectively, these findings indicate that the emergence of negative affect in this preclinical model is not dependent on cocaine dose.

  9. Reaction mechanism for cocaine esterase-catalyzed hydrolyses of (+)- and (-)-cocaine: unexpected common rate-determining step.

    Science.gov (United States)

    Liu, Junjun; Zhao, Xinyun; Yang, Wenchao; Zhan, Chang-Guo

    2011-05-05

    First-principles quantum mechanical/molecular mechanical free energy calculations have been performed to examine the catalytic mechanism for cocaine esterase (CocE)-catalyzed hydrolysis of (+)-cocaine in comparison with CocE-catalyzed hydrolysis of (-)-cocaine. It has been shown that the acylation of (+)-cocaine consists of nucleophilic attack of the hydroxyl group of Ser117 on the carbonyl carbon of (+)-cocaine benzoyl ester and the dissociation of (+)-cocaine benzoyl ester. The first reaction step of deacylation of (+)-cocaine, which is identical to that of (-)-cocaine, is rate-determining, indicating that CocE-catalyzed hydrolyses of (+)- and (-)-cocaine have a common rate-determining step. The computational results predict that the catalytic rate constant of CocE against (+)-cocaine should be the same as that of CocE against (-)-cocaine, in contrast with the remarkable difference between human butyrylcholinesterase-catalyzed hydrolyses of (+)- and (-)-cocaine. The prediction has been confirmed by experimental kinetic analysis on CocE-catalyzed hydrolysis of (+)-cocaine in comparison with CocE-catalyzed hydrolysis of (-)-cocaine. The determined common rate-determining step indicates that rational design of a high-activity mutant of CocE should be focused on the first reaction step of the deacylation. Furthermore, the obtained mechanistic insights into the detailed differences in the acylation between the (+)- and (-)-cocaine hydrolyses provide indirect clues for rational design of amino acid mutations that could more favorably stabilize the rate-determining transition state in the deacylation and, thus, improve the catalytic activity of CocE. This study provides a valuable mechanistic base for rational design of an improved esterase for therapeutic treatment of cocaine abuse.

  10. N-Acetylcysteine reduces cocaine-cue attentional bias and differentially alters cocaine self-administration based on dosing order.

    Science.gov (United States)

    Levi Bolin, B; Alcorn, Joseph L; Lile, Joshua A; Rush, Craig R; Rayapati, Abner O; Hays, Lon R; Stoops, William W

    2017-09-01

    Disrupted glutamate homeostasis is thought to contribute to cocaine-use disorder, in particular, by enhancing the incentive salience of cocaine stimuli. n-Acetylcysteine might be useful in cocaine-use disorder by normalizing glutamate function. In prior studies, n-acetylcysteine blocked the reinstatement of cocaine seeking in laboratory animals and reduced the salience of cocaine stimuli and delayed relapse in humans. The present study determined the ability of maintenance on n-acetylcysteine (0 or 2400mg/day, counterbalanced) to reduce the incentive salience of cocaine stimuli, as measured by an attentional bias task, and attenuate intranasal cocaine self-administration (0, 30, and 60mg). Fourteen individuals (N=14) who met criteria for cocaine abuse or dependence completed this within-subjects, double-blind, crossover-design study. Cocaine-cue attentional bias was greatest following administration of 0mg cocaine during placebo maintenance, and was attenuated by n-acetylcysteine. Cocaine maintained responding during placebo and n-acetylcysteine maintenance, but the reinforcing effects of cocaine were significantly attenuated across both maintenance conditions in participants maintained on n-acetylcysteine first compared to participants maintained on placebo first. These results collectively suggest that a reduction in the incentive salience of cocaine-related stimuli during n-acetylcysteine maintenance may be accompanied by reductions in cocaine self-administration. These results are in agreement with, and link, prior preclinical and clinical trial results suggesting that n-acetylcysteine might be useful for preventing cocaine relapse by attenuating the incentive salience of cocaine cues. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Prenatal exposure to recreational drugs affects global motion perception in preschool children.

    Science.gov (United States)

    Chakraborty, Arijit; Anstice, Nicola S; Jacobs, Robert J; LaGasse, Linda L; Lester, Barry M; Wouldes, Trecia A; Thompson, Benjamin

    2015-11-19

    Prenatal exposure to recreational drugs impairs motor and cognitive development; however it is currently unknown whether visual brain areas are affected. To address this question, we investigated the effect of prenatal drug exposure on global motion perception, a behavioural measure of processing within the dorsal extrastriate visual cortex that is thought to be particularly vulnerable to abnormal neurodevelopment. Global motion perception was measured in one hundred and forty-five 4.5-year-old children who had been exposed to different combinations of methamphetamine, alcohol, nicotine and marijuana prior to birth and 25 unexposed children. Self-reported drug use by the mothers was verified by meconium analysis. We found that global motion perception was impaired by prenatal exposure to alcohol and improved significantly by exposure to marijuana. Exposure to both drugs prenatally had no effect. Other visual functions such as habitual visual acuity and stereoacuity were not affected by drug exposure. Prenatal exposure to methamphetamine did not influence visual function. Our results demonstrate that prenatal drug exposure can influence a behavioural measure of visual development, but that the effects are dependent on the specific drugs used during pregnancy.

  12. Motivated Attention to Cocaine and Emotional Cues in Abstinent and Current Cocaine Users: An ERP Study

    Science.gov (United States)

    Dunning, Jonathan P.; Parvaz, Muhammad A.; Hajcak, Greg; Maloney, Thomas; Alia-Klein, Nelly; Woicik, Patricia A.; Telang, Frank; Wang, Gene-Jack; Volkow, Nora D.; Goldstein, Rita Z.

    2011-01-01

    Event-related potentials (ERPs) are a direct measure of neural activity and are ideally suited to study the time-course of attentional engagement with emotional and drug-related stimuli in addiction. In particular, the late positive potential (LPP) appears enhanced following cocaine-related compared to neutral stimuli in individuals with cocaine use disorders (CUD). However, previous studies have not directly compared cocaine-related to emotional stimuli while examining potential differences between abstinent and current cocaine users. The present study examined ERPs in 55 CUD (27 abstinent and 28 current users) and 29 matched healthy controls while they passively viewed pleasant, unpleasant, neutral, and cocaine-related pictures. To examine the time-course of attention to these stimuli, we analyzed both an early and later window in the LPP as well as the early posterior negativity (EPN), established in assessing motivated attention. Cocaine pictures elicited increased electrocortical measures of motivated attention in ways similar to affectively pleasant and unpleasant pictures in all CUD, an effect that was no longer discernible during the late LPP window for the current users. This group also exhibited deficient processing of the other emotional stimuli (early LPP window: pleasant pictures; late LPP window: pleasant and unpleasant pictures). Results were unique to the LPP and not EPN. Taken together, results support a relatively early attention bias to cocaine stimuli in cocaine addicted individuals further suggesting that recent cocaine use decreases such attention bias during later stages of processing but at the expense of deficient processing of other emotional stimuli. PMID:21450043

  13. Fundamental reaction mechanism and free energy profile for (-)-cocaine hydrolysis catalyzed by cocaine esterase.

    Science.gov (United States)

    Liu, Junjun; Hamza, Adel; Zhan, Chang-Guo

    2009-08-26

    The fundamental reaction mechanism of cocaine esterase (CocE)-catalyzed hydrolysis of (-)-cocaine and the corresponding free energy profile have been studied by performing pseudobond first-principles quantum mechanical/molecular mechanical free energy (QM/MM-FE) calculations. On the basis of the QM/MM-FE results, the entire hydrolysis reaction consists of four reaction steps, including the nucleophilic attack on the carbonyl carbon of (-)-cocaine benzoyl ester by the hydroxyl group of Ser117, dissociation of (-)-cocaine benzoyl ester, nucleophilic attack on the carbonyl carbon of (-)-cocaine benzoyl ester by water, and finally dissociation between the (-)-cocaine benzoyl group and Ser117 of CocE. The third reaction step involving the nucleophilic attack of a water molecule was found to be rate-determining, which is remarkably different from (-)-cocaine hydrolysis catalyzed by wild-type butyrylcholinesterase (BChE; where the formation of the prereactive BChE-(-)-cocaine complex is rate-determining) or its mutants containing Tyr332Gly or Tyr332Ala mutation (where the first chemical reaction step is rate-determining). Besides, the role of Asp259 in the catalytic triad of CocE does not follow the general concept of the "charge-relay system" for all serine esterases. The free energy barrier calculated for the rate-determining step of CocE-catalyzed hydrolysis of (-)-cocaine is 17.9 kcal/mol, which is in good agreement with the experimentally derived activation free energy of 16.2 kcal/mol. In the present study, where many sodium ions are present, the effects of counterions are found to be significant in determining the free energy barrier. The finding of the significant effects of counterions on the free energy barrier may also be valuable in guiding future mechanistic studies on other charged enzymes.

  14. Cocaine residue in plasma, cardiac and tracheal tissues of chronic cocaine-treated guinea-pigs

    Directory of Open Access Journals (Sweden)

    Malinee Wongnawa

    2010-03-01

    Full Text Available Supersensitivity of adrenoceptors to catecholamines is one of the mechanisms of cocaine-related cardiac complication. The precise mechanism of cocaine enhancing supersensitivity of adrenoceptors is unconcluded. The aim of this study was todetermine the levels of cocaine in plasma, cardiac and tracheal tissues in order to correlate with the supersensitivity ofadrenoceptors to catecholamines. In this study, two groups of ten guinea-pigs each were injected with 2.5 mg/kg cocaine or normal saline solution intraperitoneally twice daily for 14 days. After 24 hours of cocaine cessation, the cocaine levels in plasma, cardiac and tracheal tissues were determined using high performance liquid chromatography. The results showed that the cocaine levels in plasma and tracheal smooth muscle were 5.08±0.63 ng/ml and 2.8±0.41 ng/mg, respectively, while those in atria and ventricle were lower than 17.5 ng/g and 3.8 ng/g, respectively. These levels were less than the level that had been reported to block norepinephrine uptake (more than 30.34 ng/ml. Moreover, it had been demonstrated that cocainetreatment in the same condition as the present study produced supersensitivity to norepinephrine and epinephrine in isolatedguinea-pig atria as well as in trachea which is almost entirely not innervated by the adrenergic nerves. In addition, supersensitivityto oxymetazoline, isoproterenol and salbutamol which are not the substrates of neuronal reuptake were also demonstrated. All these data support the postsynaptic mechanism of cocaine enhancing supersensitivity which might be correlated with cardiac complication in chronic cocaine use.

  15. Reduced metabolism in brain "control networks" following cocaine-cues exposure in female cocaine abusers.

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    Full Text Available OBJECTIVE: Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved. METHOD: To test this we compared brain metabolism (using PET and ¹⁸FDG between female (n = 10 and male (n = 16 active cocaine abusers when they watched a neutral video (nature scenes versus a cocaine-cues video. RESULTS: Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05; females significantly decreased metabolism (-8.6%±10 whereas males tended to increase it (+5.5%±18. SPM analysis (Cocaine-cues vs Neutral in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001 whereas males showed increases in right inferior frontal gyrus (BA 44/45 (only at p<0.005. The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001 in frontal (BA 8, 9, 10, anterior cingulate (BA 24, 32, posterior cingulate (BA 23, 31, inferior parietal (BA 40 and thalamus (dorsomedial nucleus. CONCLUSIONS: Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from "control networks" (prefrontal, cingulate, inferior parietal, thalamus in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition. This highlights the importance of gender tailored interventions for cocaine addiction.

  16. Prenatal diagnosis of hemimegalencephaly.

    Science.gov (United States)

    Lang, Shih-Shan; Goldberg, Ethan; Zarnow, Deborah; Johnson, Mark P; Storm, Phillip B; Heuer, Gregory G

    2014-01-01

    In recent literature, there have been case reports of prenatal diagnosis of hemimegalencephaly, an extremely rare entity characterized by enlargement of all or portions of 1 cerebral hemisphere and intractable seizures. A unique case is presented of hemimegalencephaly of a fetus diagnosed in utero. A 27-year-old woman presented at 32 weeks' gestation for fetal magnetic resonance imaging after an abnormal fetal ultrasound. Fetal magnetic resonance imaging showed hemimegalencephaly of the left cerebral hemisphere with abnormal gyration. The patient was born via cesarean section at 39 weeks' gestation. He had continuous infantile spasms and partial-onset seizures starting on day 1 of life, and electroencephalography showed burst suppression. The patient's seizures were initially managed with antiepileptics, prednisolone, and a ketogenic diet; however, he was hospitalized multiple times because of status epilepticus. At 6 months of age, he underwent a successful anatomic left hemispherectomy. In utero diagnosis of complex developmental brain anomalies allows a multidisciplinary approach to provide optimal prenatal patient treatment and parental counseling. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Randomized, Double Blind, Placebo-Controlled Trial of Disulfiram for the Treatment of Cocaine Dependence in Methadone-Stabilized Patients1

    Science.gov (United States)

    Oliveto, Alison; Poling, James; Mancino, Michael J.; Feldman, Zachary; Cubells, Joseph F.; Pruzinsky, Rhonda; Gonsai, Kishorchandra; Cargile, Christopher; Sofuoglu, Mehmet; Chopra, Mohit P.; Gonzalez-Haddad, Gerardo; Carroll, Kathleen M.; Kosten, Thomas R.

    2010-01-01

    This study examined the dose-related efficacy of disulfiram for treating cocaine dependence in methadone-stabilized cocaine dependent participants. Design One hundred sixty-one cocaine-and opioid-dependent volunteers were entered into a 14-week, double blind, randomized, placebo-controlled clinical trial at two sites. Methods Participants were stabilized on methadone during weeks 1–2 and received disulfiram at 0, 62.5, 125 or 250 mg/day during weeks 3–14. All participants also received weekly cognitive behavioral therapy. Thrice-weekly urine samples and weekly self-reported drug use assessments were obtained. Results Baseline subject characteristics, retention and drug use did not differ across groups. Outcome analyses were performed on those who participated beyond week 2. Opioid positive urine samples and self-reported opioid use did not differ by treatment group. The prevalence of alcohol use was low prior to and during the trial and did not differ by treatment group. Cocaine-positive urines increased over time in the 62.5 and 125 mg disulfiram groups and decreased over time in the 250 mg disulfiram and placebo groups (p<0.0001). Self-reported cocaine use increased in the 125 mg disulfiram group relative to the other three treatment groups (p=0.04). Conclusions Disulfiram may be contraindicated for cocaine dependence at doses less than 250 mg/day. Whether disulfiram at higher doses is efficacious in reducing cocaine use in dually cocaine and opioid dependent individuals needs to be determined. PMID:20828943

  18. Cocaine in blood of coca chewers.

    Science.gov (United States)

    Homstedt, B; Lindgren, J E; Rivier, L; Plowman, T

    1979-01-01

    Coca leaves (Erythroxylum coca Lamarck) and powder (5 - 10 g) were taken orally by human subjects in the same way as South American natives do. The cocaine, as measured by mass fragmentography, was immediately detected in the blood, reached peak concentrations from 10 - 150 ng/ml plasma at 0.38 - 1.95 hours, and persisted in the plasma for more than 7 hours. Half-lives of the elimination of cocaine were calculated and ranged from 1.0 to 1.9 hours. The absorption half-lives ranged from 0.2 to 0.6 hours. The shape of the curves fits with the subjective effects reported. There is no reason to believe that the stimulating effect achieved by the use of either coca leaves or powder is not due to cocaine.

  19. COKE LIVe: recurrent vasculitis secondary to cocaine contaminated with levamisole.

    Science.gov (United States)

    Sandys, Vicki; Mahabir, Shanti; Byrne, Declan; Wynne, Bairbre

    2016-01-01

    Levamisole-induced vasculitis (LIV) is becoming an increasingly common entity secondary to both rising cocaine use in the UK and high levels of adulteration of cocaine with various contaminants. We report the first documented case of LIV secondary to adulterated cocaine in Ireland, which presented as a 6-year history of recurrent vasculitis of unknown aetiology. Classically, LIV is diagnosed by a combination of positive ANCA serology and agranulocytosis however, given the frequency of cocaine use, we urge acute physicians to consider the diagnosis in cases of typical retiform (angulated) purpura in association with a history of cocaine use.

  20. MDMA reinstates cocaine-seeking behaviour in mice.

    Science.gov (United States)

    Trigo, José Manuel; Orejarena, Maria Juliana; Maldonado, Rafael; Robledo, Patricia

    2009-06-01

    MDMA effects are mediated by monoaminergic systems, which seem to play a central role in cocaine craving and relapse. CD1 mice trained to self-administer cocaine (1 mg/kg/infusion) underwent an extinction procedure in which the cues contingent with drug self-administration remained present. Mice achieving extinction were injected with MDMA (10 mg/kg), d-amphetamine (1 and 2 mg/kg) or saline and tested for reinstatement. Acute MDMA, but not d-amphetamine or saline reinstated cocaine-seeking behaviour in mice in which cocaine self-administration and contingent cues were previously extinguished. Acute MDMA can reinstate cocaine-seeking behaviour in mice.

  1. Vaccines against stimulants: cocaine and MA

    Science.gov (United States)

    Kosten, Thomas; Domingo, Coreen; Orson, Frank; Kinsey, Berma

    2014-01-01

    While the worldwide prevalence of cocaine use remains significant, medications, or small molecule approaches, to treat drug addictions have met with limited success. Anti-addiction vaccines, on the other hand, have demonstrated great potential for treating drug abuse using a distinctly different mechanism of eliciting an antibody response that blocks the pharmacological effects of drugs. We provide a review of vaccine-based approaches to treating stimulant addictions; specifically and cocaine addictions. This selective review article focuses on the one cocaine vaccine that has been into clinical trials and presents new data related to pre-clinical development of a methamphetamine (MA) vaccine. We also review the mechanism of action for vaccine induced antibodies to abused drugs, which involves kinetic slowing of brain entry as well as simple blocking properties. We present pre-clinical innovations for MA vaccines including hapten design, linkage to carrier proteins and new adjuvants beyond alum. We provide some new information on hapten structures and linkers and variations in protein carriers. We consider a carrier, outer membrance polysaccharide coat protein (OMPC), that provides some self-adjuvant through lipopolysaccharide components and provide new results with a monophosopholipid adjuvant for the more standard carrier proteins with cocaine and MA. The review then covers the clinical trials with the cocaine vaccine TA-CD. The clinical prospects for advances in this field over the next few years include a multi-site cocaine vaccine clinical trial to be reported in 2013 and phase 1 clinical trials of a MA vaccine in 2014. PMID:23509915

  2. Fetal alcohol syndrome – causes, diagnostic criteria and prevalence

    Directory of Open Access Journals (Sweden)

    Agata Horecka-Lewitowicz

    2014-04-01

    Full Text Available Fetal alcohol syndrome (FAS is the outcome of alcohol exposition in the prenatal period. It is irreversible. In Poland, FAS is becoming more and more common, the diagnostic tools are limited though. It is recommended to use the 4-Digit Diagnostic Code, which evaluates the 4 basic FAS symptoms: growth retardation, dysmorphic appearance, damage to the central nervous system and prenatal alcohol exposure. It has been confirmed that there is no safe amount of alcohol for a mother to drink while carrying a baby. To put it another way, only a complete lack of alcohol consumption is a guarantee that the baby will not suffer from FAS. It is necessary for society to know that even the smallest amount of alcohol is bad for the foetus. A number of people still believe that, for example, red wine is good and healthy for both the mother and child.

  3. Polysomnographic Sleep Dysregulation in Cocaine Dependence

    Directory of Open Access Journals (Sweden)

    Edwin M. Valladares

    2007-01-01

    Full Text Available Insomnia and sleep disturbance are associated with declines in health functioning, alongwith increases in mortality risk. Given the prominence of reported sleep disturbance incocaine-dependent subjects and persistence into recovery, understanding the natureand severity of these disturbances in this population may help to identify relevantpathways that contribute to the increased mortality in cocaine dependence. Polysomnography provides a means of objectively characterizing sleep and, in turn, sleep disturbances. Few studies have used polysomnography to evaluate sleep incocaine-dependent persons, yet these studies have the potential to advance treatmentsthat will ultimately reduce morbidity in cocaine-dependent subjects.

  4. Internuclear Ophthalmoplegia Secondary to Cocaine Abuse

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    Richard L. Rabin

    2017-01-01

    Full Text Available Purpose. To report a case of internuclear ophthalmoplegia (INO caused by cocaine. Method. We report a case of a 54-year-old female who presented with a left INO three days after snorting cocaine, and we review the literature. Results. MRI of the brain demonstrated several small abnormal foci in the pons on FLAIR and diffusion weighted imaging consistent with ischemic infarction. The patient’s symptoms remained stable throughout her hospitalization. She was sent to a rehabilitation facility and was lost to follow-up. Conclusion. In cases of extraocular movement abnormalities, it is important to inquire about recreational drug use.

  5. An Overview of the Mechanisms of Abnormal GABAergic Interneuronal Cortical Migration Associated with Prenatal Ethanol Exposure.

    Science.gov (United States)

    Shenoda, Botros B

    2017-02-03

    GABAergic Interneuronal migration constitutes an essential process during corticogenesis. Derived from progenitor cells located in the proliferative zones of the ventral telencephalon, newly generated GABAergic Interneuron migrate to their cortical destinations. Cortical dysfunction associated with defects in neuronal migration results in severe developmental consequences. There is growing evidence linking prenatal ethanol exposure to abnormal GABAergic interneuronal migration and subsequent cortical dysfunction. Investigating the pathophysiological mechanisms behind disrupted GABAergic interneuronal migration encountered with prenatal alcohol exposure is crucial for understanding and managing fetal alcohol spectrum disorders. This review explores the molecular pathways regulating GABAergic interneuronal cortical migration that might be altered by prenatal ethanol exposure thus opening new avenues for further research in this topic.

  6. Can ropinirole modulate reinforcing subjective effects of cocaine in humans?

    Directory of Open Access Journals (Sweden)

    Angelo Giovanni Icro eMaremmani

    2011-08-01

    Full Text Available In this study we evaluated, by means of the Cocaine Rush Visual Analogue Scale (CRVAS, the impact of ropinirole on the expected rush induced by cocaine in a group of heroin addicts abusing cocaine; the self-reported reaction to the rush blockade (if any on cocaine consumption, and the correlations between this self-reported reaction and individual, clinical and therapeutic parameters. Nineteen cocaine abuser heroin-dependent patients entered the study. Their experienced cocaine rush was 61.31±32.1% of the maximum effect previously experienced. Compared with their previous rush intensity 16 patients experienced significantly lower intensity, three the same intensity and none a higher intensity. In particular, two patients experienced a complete blockade of rush and reported a reduced use of cocaine. Fourteen patients experienced a partial blockade of cocaine rush; of these, nine reported they had reduced their use of cocaine. Ropinirole does diminish the subjective intensity of an expected cocaine rush, so interfering with the dynamics of reward, while supporting its possible use in the treatment of cocaine dependence.

  7. Sensitive method for detection of cocaine and associated analytes by liquid chromatography-tandem mass spectrometry in urine.

    Science.gov (United States)

    Langman, Loralie J; Bjergum, Matthew W; Williamson, Christopher L; Crow, Frank W

    2009-10-01

    Cocaine (COC) is a potent CNS stimulant that is metabolized to benzoylecgonine (BE) and further metabolized to minor metabolites such as m-hydroxybenzoylecgonine (m-HOBE). COC is also metabolized to norcocaine (NC). Cocaethylene (CE) is formed when cocaine and ethyl alcohol are used simultaneously. Anhydroecgonine methyl ester (AEME) is a unique marker following smoked cocaine, and anhydroecgonine ethyl ester (AEEE) is found in cocaine smokers who also use ethyl alcohol. We developed a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for the detection and quantitation of COC, BE, NC, CE, m-HOBE, AEME, and AEEE in urine. Two hundred samples previously analyzed by gas chromatography (GC) coupled with MS were extracted using solid-phase extraction. Chromatographic separation was achieved using a gradient consisting of mobile phase A [20 mM ammonium formate (pH 2.7)] and mobile phase B (methanol/acetonitrile, 50:50), an XDB-C(8) (50 x 2.1 mm, 1.8 microm) column and a flow rate of 270 microL/min. Concentrations were calculated by comparing the peak-area with the internal standard and plotted against a standard curve. The assay displayed linearity from 1.0 to 100 ng/mL. Within- and between-run coefficients of variation were < 10% throughout the linear range. A method comparison between GC-MS and LC-MS-MS showed good correlation for COC (r(2) = 0.982) and BE (r(2) = 0.955). We report here on a sensitive method to identify clinically and forensically relevant cocaine and associated analytes at concentrations as low as 1.0 ng/mL.

  8. A cocaine consumption study in Madrid from Social Psychology

    Directory of Open Access Journals (Sweden)

    Jesús Saiz Galdós

    2008-05-01

    Full Text Available Cocaine use in Spain is understood to be a serious problem, and this article reports two methodologically contrasting studies of the phenomenon. The first measures differences in eight variables (personality traits, personal values, attitudes towards cocaine consumption, subjective norms, behavioral perceived control, behavioral intention and socio-demographic and substance consumption among three groups of respondents, totaling 660 people. The groups are: cocaine users, people in treatment for cocaine dependence, and people who have never used cocaine. The results identify, as significant risk factors: perceived behavioral control, the values of Hedonism and Stimulation, and the personality trait of Impulsivity. In the second study, life stories are collected form 32 people with significant experience of cocaine use. These life stories reveal the sociocultural, leisure, competitive and consumerist factors that promote or facilitate cocaine and other substance use. Finally, the article considers theoretical and methodological issues, and makes a number of recommendations for drugs prevention policy.

  9. Prenatal management of anencephaly.

    Science.gov (United States)

    Cook, Rebecca J; Erdman, Joanna N; Hevia, Martin; Dickens, Bernard M

    2008-09-01

    About a third of anencephalic fetuses are born alive, but they are not conscious or viable, and soon die. This neural tube defect can be limited by dietary consumption of foliates, and detected prenatally by ultrasound and other means. Many laws permit abortion, on this indication or on the effects of pregnancy and prospects of delivery on a woman's physical or mental health. However, abortion is limited under some legal systems, particularly in South America. To avoid criminal liability, physicians will not terminate pregnancies, by induced birth or abortion, without prior judicial approval. Argentinian courts have developed means to resolve these cases, but responses of Brazilian courts are less clear. Ethical concerns relate to late-term abortion, meaning after the point of fetal viability, but since anencephalic fetuses are nonviable, many ethical concerns are overcome. Professional guidance is provided by several professional and institutional codes on management of anencephalic pregnancies.

  10. Dimensions of Religion, Depression Symptomatology, and Substance Use Among Rural African American Cocaine Users

    Science.gov (United States)

    Montgomery, Brooke E. E.; Stewart, Katharine E.; Bryant, Keneshia J.; Ounpraseuth, Songthip T.

    2014-01-01

    Research has shown a relationship between depression, substance use, and religiosity but, few have investigated this relationship in a community sample of drug-using African Americans. This study examined the relationship between dimensions of religion (positive and negative religious coping, private and public religious participation, religious preference, and God-based, clergy-based, and congregation-based religious support), depression symptomatology, and substance use among 223 African American cocaine users. After controlling for gender, employment, and age, greater congregation-based support and greater clergy-based support were associated with fewer reported depressive symptoms. Additionally, greater congregation-based support was associated with less alcohol use. PMID:24564561

  11. Ceftriaxone attenuates locomotor activity induced by acute and repeated cocaine exposure in mice.

    Science.gov (United States)

    Tallarida, Christopher S; Corley, Gladys; Kovalevich, Jane; Yen, William; Langford, Dianne; Rawls, Scott M

    2013-11-27

    Ceftriaxone (CTX) decreases locomotor activation produced by initial cocaine exposure and attenuates development of behavioral sensitization produced by repeated cocaine exposure. An important question that has not yet been answered is whether or not CTX reduces behavioral sensitization to cocaine in cases in which the antibiotic is administered only during the period of cocaine absence that follows repeated cocaine exposure and precedes reintroduction to cocaine. We investigated this question using C57BL/6 mice. Mice pretreated with cocaine (15mg/kg×14 days) and then challenged with cocaine (15mg/kg) after 30 days of cocaine absence displayed sensitization of locomotor activity. For combination experiments, CTX injected during the 30 days of cocaine absence attenuated behavioral sensitization produced by cocaine challenge. In the case in which CTX was injected together with cocaine for 14 days, development of behavioral sensitization to cocaine challenge was also reduced. CTX attenuated the increase in locomotor activity produced by acute cocaine exposure; however, its efficacy was dependent on the dose of cocaine as inhibition was detected against 30mg/kg, but not 15mg/kg, of cocaine. These results from mice indicate that CTX attenuates locomotor activity produced by acute and repeated cocaine exposure and counters cocaine's locomotor activating properties in a paradigm in which the antibiotic is injected during the period of forced cocaine absence that follows repeated cocaine exposure.

  12. AAVrh.10-Mediated Expression of an Anti-Cocaine Antibody Mediates Persistent Passive Immunization That Suppresses Cocaine-Induced Behavior

    Science.gov (United States)

    Rosenberg, Jonathan B.; Hicks, Martin J.; De, Bishnu P.; Pagovich, Odelya; Frenk, Esther; Janda, Kim D.; Wee, Sunmee; Koob, George F.; Hackett, Neil R.; Kaminsky, Stephen M.; Worgall, Stefan; Tignor, Nicole; Mezey, Jason G.

    2012-01-01

    Abstract Cocaine addiction is a major problem affecting all societal and economic classes for which there is no effective therapy. We hypothesized an effective anti-cocaine vaccine could be developed by using an adeno-associated virus (AAV) gene transfer vector as the delivery vehicle to persistently express an anti-cocaine monoclonal antibody in vivo, which would sequester cocaine in the blood, preventing access to cognate receptors in the brain. To accomplish this, we constructed AAVrh.10antiCoc.Mab, an AAVrh.10 gene transfer vector expressing the heavy and light chains of the high affinity anti-cocaine monoclonal antibody GNC92H2. Intravenous administration of AAVrh.10antiCoc.Mab to mice mediated high, persistent serum levels of high-affinity, cocaine-specific antibodies that sequestered intravenously administered cocaine in the blood. With repeated intravenous cocaine challenge, naive mice exhibited hyperactivity, while the AAVrh.10antiCoc.Mab-vaccinated mice were completely resistant to the cocaine. These observations demonstrate a novel strategy for cocaine addiction by requiring only a single administration of an AAV vector mediating persistent, systemic anti-cocaine passive immunity. PMID:22486244

  13. Daily stressor sensitivity, abuse effects, and cocaine use in cocaine dependence.

    Science.gov (United States)

    Waldrop, Angela E; Back, Sudie E; Brady, Kathleen T; Upadhyaya, Himanshu P; McRae, Aimee L; Saladin, Michael E

    2007-12-01

    This study highlights respondent sensitivity to daily hassles as it relates to situational cocaine use and perceived long-term effects of adverse events in childhood. Data were drawn from a larger study on stress reactivity in cocaine dependent individuals. Participants (n=104) were cocaine dependent men and women without comorbid posttraumatic stress disorder (PTSD). They completed the Early Trauma Inventory (ETI), the Daily Hassles Scale (DHS), the Inventory of Drug-Taking Situations (IDTS), and the Time-Line Follow-Back (TLFB; for 90 days prior to interview). There were no gender differences in the amount or frequency of cocaine use, although the patterns of use differed between male and female users. Overall, there were some associations in the patterns of cocaine use and sensitivity to daily hassles, particularly the use in response to conflict with others. Early negative life events were positively related to response to daily hassles, but current triggers were more relevant. Reactivity to cocaine cues was related to daily hassle sensitivity among women only. Limitations and implications of the findings are discussed.

  14. Effects of maternal cigarette smoking and cocaine use in pregnancy on fetal response to vibroacoustic stimulation and habituation.

    Science.gov (United States)

    Gingras, J L; Mitchell, E A; Grattan, K J; Stewart, A W

    2004-11-01

    Cigarette smoking and cocaine use in pregnancy are common in the US and both are risk factors for sudden infant death syndrome (SIDS). Although the cause of SIDS is not known, one postulated mechanism involves abnormalities of arousal and arousal regulation. Cigarette smoking and cocaine use may cause deficits of arousal. Many believe arousal deficits occur prenatally. The aim of this study was to assess the effects of cigarette smoke and cocaine exposure during pregnancy on measures of fetal arousal and arousal competency: 1) the fetal response to vibroacoustic stimulation (VAS) and 2) habituation to VAS. Maternal cigarette smoking and cocaine use in pregnancy are associated with altered arousal and arousal regulation in the fetus. Three groups of mother-fetal dyads were enrolled: 1) cigarette smokers (n = 54), 2) cocaine users (n = 30), and 3) controls (n = 60). One hundred eight fetuses were tested at 29-31 wk gestation, 119 at 32-35 wk, and 118 at 36+ wk. The fetal response to VAS was assessed using real-time ultrasound and a paradigm of arousal responsiveness. Responders were tested with repeated VAS to assess habituation. Also, the quality of fetal reactivity to repeated stimuli was assessed as a measure of arousal and arousal regulation competence (Behavioral Reactivity Scale). The control group had a larger proportion of fetuses who were too active to initiate testing ("too active to test") (p = 0.013); the proportion of fetuses too active to test decreased with increasing gestational age. The majority of the fetuses who could be tested responded to the initial VAS, and there were no group differences. The proportion of fetuses that habituated and the rate of habituation did not differ between the groups. Behavioral reactivity did not differ between groups. The original hypotheses were not confirmed. However, the chosen assessment paradigms may have lacked sensitivity. The proportion of fetuses that were "too active to test" decreased with gestational age

  15. What Happens during Prenatal Visits?

    Science.gov (United States)

    ... at risk for complications? How does stress affect pregnancy? NICHD Research Information Clinical Trials Resources and Publications What happens during prenatal visits? Skip sharing on social media links Share this: Page Content What happens during ...

  16. Preconception Care and Prenatal Care

    Science.gov (United States)

    ... at risk for complications? How does stress affect pregnancy? NICHD Research Information Clinical Trials Resources and Publications Preconception Care and Prenatal Care: Condition Information Skip sharing on social media links Share this: Page Content What is preconception ...

  17. Prenatal Tests for Down Syndrome

    Science.gov (United States)

    ... PRENATAL TESTS FOR DOWN SYNDROME What Is Down Syndrome? Down syndrome is a common birth defect that includes mental retardation and— often— heart problems. Children with Down syndrome have round faces and almond-shaped eyes that ...

  18. Case Study: The Chemistry of Cocaine

    Science.gov (United States)

    Dewprashad, Brahmadeo

    2011-01-01

    This column provides original articles on innovations in case study teaching, assessment of the method, as well as case studies with teaching notes. This month's case study focuses on the chemistry of cocaine to teach a number of core concepts in organic chemistry. It also requires that students read and analyze an original research paper on…

  19. Cocaine-induced pulmonary changes: HRCT findings

    Directory of Open Access Journals (Sweden)

    Renata Rocha de Almeida

    2015-08-01

    Full Text Available AbstractObjective: To evaluate HRCT scans of the chest in 22 patients with cocaine-induced pulmonary disease.Methods: We included patients between 19 and 52 years of age. The HRCT scans were evaluated by two radiologists independently, discordant results being resolved by consensus. The inclusion criterion was an HRCT scan showing abnormalities that were temporally related to cocaine use, with no other apparent causal factors.Results:In 8 patients (36.4%, the clinical and tomographic findings were consistent with "crack lung", those cases being studied separately. The major HRCT findings in that subgroup of patients included ground-glass opacities, in 100% of the cases; consolidations, in 50%; and the halo sign, in 25%. In 12.5% of the cases, smooth septal thickening, paraseptal emphysema, centrilobular nodules, and the tree-in-bud pattern were identified. Among the remaining 14 patients (63.6%, barotrauma was identified in 3 cases, presenting as pneumomediastinum, pneumothorax, and hemopneumothorax, respectively. Talcosis, characterized as perihilar conglomerate masses, architectural distortion, and emphysema, was diagnosed in 3 patients. Other patterns were found less frequently: organizing pneumonia and bullous emphysema, in 2 patients each; and pulmonary infarction, septic embolism, eosinophilic pneumonia, and cardiogenic pulmonary edema, in 1 patient each.Conclusions: Pulmonary changes induced by cocaine use are varied and nonspecific. The diagnostic suspicion of cocaine-induced pulmonary disease depends, in most of the cases, on a careful drawing of correlations between clinical and radiological findings.

  20. Case Study: The Chemistry of Cocaine

    Science.gov (United States)

    Dewprashad, Brahmadeo

    2011-01-01

    This column provides original articles on innovations in case study teaching, assessment of the method, as well as case studies with teaching notes. This month's case study focuses on the chemistry of cocaine to teach a number of core concepts in organic chemistry. It also requires that students read and analyze an original research paper on…

  1. Cocaine-induced pulmonary changes: HRCT findings *

    Science.gov (United States)

    de Almeida, Renata Rocha; Zanetti, Gláucia; Souza, Arthur Soares; de Souza, Luciana Soares; Silva, Jorge Luiz Pereira e; Escuissato, Dante Luiz; Irion, Klaus Loureiro; Mançano, Alexandre Dias; Nobre, Luiz Felipe; Hochhegger, Bruno; Marchiori, Edson

    2015-01-01

    Abstract Objective: To evaluate HRCT scans of the chest in 22 patients with cocaine-induced pulmonary disease. Methods: We included patients between 19 and 52 years of age. The HRCT scans were evaluated by two radiologists independently, discordant results being resolved by consensus. The inclusion criterion was an HRCT scan showing abnormalities that were temporally related to cocaine use, with no other apparent causal factors. Results: In 8 patients (36.4%), the clinical and tomographic findings were consistent with "crack lung", those cases being studied separately. The major HRCT findings in that subgroup of patients included ground-glass opacities, in 100% of the cases; consolidations, in 50%; and the halo sign, in 25%. In 12.5% of the cases, smooth septal thickening, paraseptal emphysema, centrilobular nodules, and the tree-in-bud pattern were identified. Among the remaining 14 patients (63.6%), barotrauma was identified in 3 cases, presenting as pneumomediastinum, pneumothorax, and hemopneumothorax, respectively. Talcosis, characterized as perihilar conglomerate masses, architectural distortion, and emphysema, was diagnosed in 3 patients. Other patterns were found less frequently: organizing pneumonia and bullous emphysema, in 2 patients each; and pulmonary infarction, septic embolism, eosinophilic pneumonia, and cardiogenic pulmonary edema, in 1 patient each. Conclusions: Pulmonary changes induced by cocaine use are varied and nonspecific. The diagnostic suspicion of cocaine-induced pulmonary disease depends, in most of the cases, on a careful drawing of correlations between clinical and radiological findings. PMID:26398752

  2. Vulnerability to cocaine : role of stress hormones

    NARCIS (Netherlands)

    Jong, Inge Elisabeth Maria de

    2007-01-01

    Not everyone who experiments with cocaine acquires compulsive drug use. The mechanism underlying this individual difference in susceptibility to addiction is poorly understood. Recent studies have identified genes and adverse life events (stress) as risk factors. The objective of this thesis is to i

  3. Cocaine-induced pulmonary changes: HRCT findings

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Renata Rocha de; Zanetti, Glaucia; Marchiori, Edson, E-mail: edmarchiori@gmail.com [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Programa de Pos-Graduacao em Radiologia; Souza Junior, Arthur Soares [Faculdade de Medicina de Petropolis, Petropolis, RJ (Brazil); Souza, Luciana Soares de [Ultra-X, Sao Jose do Rio Preto, SP (Brazil); Silva, Jorge Luiz Pereira e [Universidade Federal da Bahia (UFBA), Salvador (Brazil). Dep. de Medicina e Apoio Diagnostico; Escuissato, Dante Luiz [Universidade Federal do Parana (UFPR), Curitiba (Brazil). Dept. de Clinica Medica; Irion, Klaus Loureiro [Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool (United Kingdom); Mancano, Alexandre Dias [Hospital Anchieta, Taguatinga, DF (Brazil); Nobre, Luiz Felipe [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil); Hochhegger, Bruno [Universidade Federal de Ciencias da Saude de Porto Alegre, Porto Alegre, RS (Brazil); Marchiori, Edson [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil)

    2015-07-15

    Objective: To evaluate HRCT scans of the chest in 22 patients with cocaine-induced pulmonary disease. Methods: We included patients between 19 and 52 years of age. The HRCT scans were evaluated by two radiologists independently, discordant results being resolved by consensus. The inclusion criterion was an HRCT scan showing abnormalities that were temporally related to cocaine use, with no other apparent causal factors. Results: In 8 patients (36.4%), the clinical and tomographic findings were consistent with 'crack lung', those cases being studied separately. The major HRCT findings in that subgroup of patients included ground-glass opacities, in 100% of the cases; consolidations, in 50%; and the halo sign, in 25%. In 12.5% of the cases, smooth septal thickening, paraseptal emphysema, centrilobular nodules, and the tree-in-bud pattern were identified. Among the remaining 14 patients (63.6%), barotrauma was identified in 3 cases, presenting as pneumomediastinum, pneumothorax, and hemopneumothorax, respectively. Talcosis, characterized as perihilar conglomerate masses, architectural distortion, and emphysema, was diagnosed in 3 patients. Other patterns were found less frequently: organizing pneumonia and bullous emphysema, in 2 patients each; and pulmonary infarction, septic embolism, eosinophilic pneumonia, and cardiogenic pulmonary edema, in 1 patient each. Conclusions: Pulmonary changes induced by cocaine use are varied and nonspecific. The diagnostic suspicion of cocaine-induced pulmonary disease depends, in most of the cases, on a careful drawing of correlations between clinical and radiological findings. (author)

  4. Eyeblink Classical Conditioning in Alcoholism and Fetal Alcohol Spectrum Disorders.

    Science.gov (United States)

    Cheng, Dominic T; Jacobson, Sandra W; Jacobson, Joseph L; Molteno, Christopher D; Stanton, Mark E; Desmond, John E

    2015-01-01

    Alcoholism is a debilitating disorder that can take a significant toll on health and professional and personal relationships. Excessive alcohol consumption can have a serious impact on both drinkers and developing fetuses, leading to long-term learning impairments. Decades of research in laboratory animals and humans have demonstrated the value of eyeblink classical conditioning (EBC) as a well-characterized model system to study the neural mechanisms underlying associative learning. Behavioral EBC studies in adults with alcohol use disorders and in children with fetal alcohol spectrum disorders report a clear learning deficit in these two patient populations, suggesting alcohol-related damage to the cerebellum and associated structures. Insight into the neural mechanisms underlying these learning impairments has largely stemmed from laboratory animal studies. In this mini-review, we present and discuss exemplary animal findings and data from patient and neuroimaging studies. An improved understanding of the neural mechanisms underlying learning deficits in EBC related to alcoholism and prenatal alcohol exposure has the potential to advance the diagnoses, treatment, and prevention of these and other pediatric and adult disorders.

  5. Block of a Ca(2+)-activated potassium channel by cocaine.

    Science.gov (United States)

    Premkumar, L S

    2005-04-01

    The primary target for cocaine is believed to be monoamine transporters because of cocaine's high-affinity binding that prevents re-uptake of released neurotransmitter. However, direct interaction with ion channels has been shown to be important for certain pharmacological/toxicological effects of cocaine. Here I show that cocaine selectively blocks a calcium-dependent K(+) channel in hippocampal neurons grown in culture (IC(50)=approximately 30 microM). Single-channel recordings show that in the presence of cocaine, the channel openings are interrupted with brief closures (flicker block). As the concentration of cocaine is increased the open-time is reduced, whereas the duration of brief closures is independent of concentration. The association and dissociation rate constants of cocaine for the neuronal Ca(2+)-activated K(+ )channels are 261+/-37 microM: (-1)s(-1) and 11451+/-1467 s(-1). The equilibrium dissociation constant (K(B)) for cocaine, determined from single-channel parameters, is 43 microM. The lack of voltage dependence of block suggests that cocaine probably binds to a site at the mouth of the pore. Block of Ca(2+)-dependent K(+) channels by cocaine may be involved in functions that include broadening of the action potential, which would facilitate transmitter release, enhancement of smooth muscle contraction particularly in blood vessels, and modulation of repetitive neuronal firing by altering the repolarization and afterhyperpolarization phases of the action potential.

  6. Cocaine-Associated Seizures and Incidence of Status Epilepticus

    Directory of Open Access Journals (Sweden)

    Majlesi, Nima DO

    2010-05-01

    Full Text Available Objectives: Acute complications from cocaine abuse are commonly treated in the emergency department (ED; one of the most consequential is status epilepticus. The incidence of this complication is not clearly defined in the prior literature on cocaine-associated sequelae. We evaluated the incidence of status epilepticus in patients with seizures secondary to suspected cocaine use.Methods: We performed a retrospective multi-center study of patients with seizures resulting from cocaine use. We identified study subjects at 15 hospitals by record review and conducted a computer-assisted records search to identify patients with seizures for each institution over a four-year period. We selected subjects from this group on the basis of cocaine use and determined the occurrence of status epilepticus among them. Data were collected on each subject using a standardized data collection form.Results: We evaluated 43 patients in the ED for cocaine-associated seizures. Their age range was 17 to 54, with a mean age was 31 years; 53% were male. Of 43 patients, 42 experienced a single tonic-clonic seizure and one developed status epilepticus. All patients had either a history of cocaine use or positive urine drug screen for cocaine.Conclusion: Despite reported cases of status epilepticus with cocaine-induced seizures, the incidence of this complication was unclear based on prior literature. This study shows that most cocaine-associated seizures are self-limited. [West J Emerg Med. 2010; 11(2:157-160.

  7. Varenicline effects on cocaine self administration and reinstatement behavior.

    Science.gov (United States)

    Guillem, Karine; Peoples, Laura L

    2010-03-01

    This study tested the effects of the nicotine addiction treatment varenicline on cocaine self administration (SA) and reinstatement. In one SA experiment, rats were trained to self-administer cocaine (0.75 mg/kg/infusion). Thereafter, daily SA sessions continued as before except that every fourth session was preceded by a presession injection of varenicline (0.0, 0.3, 1.0 and 2.0 mg/kg, SC, 50-min presession). In three reinstatement experiments, animals were exposed sequentially to SA training, extinction training, and several reinstatement test sessions. In two of the reinstatement experiments, cocaine-seeking was reinstated by presentation of cocaine-predictive cues at the onset of the test session (cue reinstatement). In a third reinstatement experiment, cocaine-seeking was reinstated by a presession injection of cocaine (drug reinstatement). Each reinstatement session was preceded by an injection of either vehicle or varenicline (dose range of 0.1-2.0 mg/kg). The SA and reinstatement experiments showed that low-dose varenicline decreases reinstatement behavior, without significantly affecting cocaine SA. In contrast, high-dose varenicline increases reinstatement of cocaine-directed behavior and decreases cocaine SA. A control study showed that sucrose-directed behavior is unaltered by varenicline. On the basis of these findings, low-varenicline doses might decrease relapse in cocaine-addicted individuals, but high doses of varenicline might have the opposite effect.

  8. Neuropsychological consequences of alcohol and drug abuse on different components of executive functions.

    Science.gov (United States)

    Fernández-Serrano, María José; Pérez-García, Miguel; Schmidt Río-Valle, Jacqueline; Verdejo-García, Antonio

    2010-09-01

    Several studies have shown alterations in different components of executive functioning in users of different drugs, including cannabis, cocaine and heroin. However, it is difficult to establish a specific association between the use of each of these drugs and executive alterations, since most drug abusers are polysubstance abusers, and alcohol is a ubiquitous confounding factor. Moreover, in order to study the association between consumption of different drugs and executive functioning, the patterns of quantity and duration of drugs used must be considered, given the association between these parameters and the executive functioning alteration degree. Based on the multicomponent approach to executive functions, the aims of the present study were: (i) to analyse the differential contribution of alcohol versus cocaine, heroin and cannabis use on executive functions performance; and (ii) to analyse the contribution made by the severity of the different drugs used (quantity and duration patterns) on these functions in a sample of polysubstance abusers that requested treatment for cannabis-, cocaine- or heroin-related problems. We administered measures of fluency, working memory, analogical reasoning, interference, cognitive flexibility, decision-making and self-regulation to two groups: 60 substance-dependent individuals (SDIs) and 30 healthy control individuals (HCIs). SDIs had significantly poorer performance than HCIs across all of the executive domains assessed. Results from hierarchical regression models showed the existence of common correlates of the use of alcohol, cannabis and cocaine on verbal fluency and decision-making; common correlates of quantity of cannabis and cocaine use on verbal working memory and analogical reasoning; common correlates of duration of cocaine and heroin use on shifting; and specific effects of duration of cocaine use on inhibition measures. These findings indicate that alcohol abuse is negatively associated with fluency and

  9. Nutrition Implications for Fetal Alcohol Spectrum Disorder12

    Science.gov (United States)

    Young, Jennifer K.; Giesbrecht, Heather E.; Eskin, Michael N.; Aliani, Michel; Suh, Miyoung

    2014-01-01

    Prenatal alcohol exposure produces a multitude of detrimental alcohol-induced defects in children collectively known as fetal alcohol spectrum disorder (FASD). Children with FASD often exhibit delayed or abnormal mental, neural, and physical growth. Socioeconomic status, race, genetics, parity, gravidity, age, smoking, and alcohol consumption patterns are all factors that may influence FASD. Optimal maternal nutritional status is of utmost importance for proper fetal development, yet is often altered with alcohol consumption. It is critical to determine a means to resolve and reduce the physical and neurological malformations that develop in the fetus as a result of prenatal alcohol exposure. Because there is a lack of information on the role of nutrients and prenatal nutrition interventions for FASD, the focus of this review is to provide an overview of nutrients (vitamin A, docosahexaenoic acid, folic acid, zinc, choline, vitamin E, and selenium) that may prevent or alleviate the development of FASD. Results from various nutrient supplementation studies in animal models and FASD-related research conducted in humans provide insight into the plausibility of prenatal nutrition interventions for FASD. Further research is necessary to confirm positive results, to determine optimal amounts of nutrients needed in supplementation, and to investigate the collective effects of multiple-nutrient supplementation. PMID:25398731

  10. Role of the 5HT3 Receptor in Alcohol Drinking and Aggression Using a Transgenic Mouse Model

    Science.gov (United States)

    2006-09-01

    IMMUNOHISTOCHEMISTRY Animals were killed with an overdose of sodium pentobarbital followed by perfusion With 4% paraformaldehyde (PFA). Brains were...pathway and drug abuse by modulating dopamine release, and brain slices from 5-HT3-OE mice release more DA in response to agonist and cocaine (79). This...fading technique.” Research Society on Alcoholism 26:531, 2002 Carta, M. Allan, A.M. Partridge, L.D. and Valenzuela, C.F. Effect of cocaine on 5HT3

  11. Myocardial uptake of cocaine and effects of cocaine on myocardial substrate utilization and perfusion in hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Som, P.; Wang, G.J. [Brookhaven National Lab., Upton, NY (United States); Oster, Z.H. [State Univ. of New York, Stony Brook, NY (United States); Knapp, F.F. Jr. [Oak Ridge National Lab., TN (United States); Yonekura, Y. [Kyoto Univ. (Japan). Faculty of Medicine; Fujibayashi, Y. [Kyoto Univ. (Japan). Hospital; Yamamoto, K. [Fukui Univ. (Japan). Medical School; Kubota, K. [Tohoku Univ., Sendai (Japan)

    1992-12-31

    Cocaine abuse is a problem causing world-wide concern and the number of deaths following cocaine use is increasing. Cardiovascular complications following cocaine include severe tachyarrythmias, pulmonary edema, myocardial infarction, and acute renal failure, which are major problems confronting emergency facilities. While the studies of cocaine effects on the brain have been given the most attention, it is clear that the effects of cocaine on the cardiovascular system are of great importance, given the increasing number of reports on sudden death and myocardial infarctions in young adults related to cocaine use. The precise mechanisms of cardiotoxic actions of cocaine are unclear. We investigated the whole-body distribution of C-14-labeled cocaine to determine the cocaine-binding sites, including blocking experiments to determine the nature of regional binding sites, and differential response of the normal vs. diseased heart (hypertensive cardiomyopathy) in an animal model to mimic a potentially high risk population. We investigated the acute effects of cocaine on myocardial metabolism using two myocardial energy substrate analogs, fatty acid and glucose with comparison with regional perfusion.

  12. Myocardial uptake of cocaine and effects of cocaine on myocardial substrate utilization and perfusion in hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Som, P.; Wang, G.J. (Brookhaven National Lab., Upton, NY (United States)); Oster, Z.H. (State Univ. of New York, Stony Brook, NY (United States)); Knapp, F.F. Jr. (Oak Ridge National Lab., TN (United States)); Yonekura, Y. (Kyoto Univ. (Japan). Faculty of Medicine); Fujibayashi, Y. (Kyoto Univ. (Japan). Hospital); Yamamoto, K. (Fukui Univ. (Japan). Medical School); Kubota, K. (Tohoku Univ., Sendai

    1992-01-01

    Cocaine abuse is a problem causing world-wide concern and the number of deaths following cocaine use is increasing. Cardiovascular complications following cocaine include severe tachyarrythmias, pulmonary edema, myocardial infarction, and acute renal failure, which are major problems confronting emergency facilities. While the studies of cocaine effects on the brain have been given the most attention, it is clear that the effects of cocaine on the cardiovascular system are of great importance, given the increasing number of reports on sudden death and myocardial infarctions in young adults related to cocaine use. The precise mechanisms of cardiotoxic actions of cocaine are unclear. We investigated the whole-body distribution of C-14-labeled cocaine to determine the cocaine-binding sites, including blocking experiments to determine the nature of regional binding sites, and differential response of the normal vs. diseased heart (hypertensive cardiomyopathy) in an animal model to mimic a potentially high risk population. We investigated the acute effects of cocaine on myocardial metabolism using two myocardial energy substrate analogs, fatty acid and glucose with comparison with regional perfusion.

  13. Mephedrone interactions with cocaine: prior exposure to ‘bath salt’ constituent enhances cocaine-induced locomotor activation in rats

    Science.gov (United States)

    Gregg, Ryan A.; Tallarida, Christopher S.; Reitz, Allen B.; Rawls, Scott M.

    2014-01-01

    Concurrent use of mephedrone (4-methylmethcathinone) (MEPH) and established drugs of abuse is now commonplace, but knowledge about interactions between these drugs is sparse. The present study was designed to test the hypothesis that prior MEPH exposure enhances the locomotor-stimulant effects of cocaine and methamphetamine (METH). For cocaine experiments, rats pretreated with saline, cocaine (15 mg/kg), or MEPH (15 mg/kg) for 5 days were injected with cocaine after 10 days of drug absence. For METH experiments, rats pretreated with saline, METH (2 mg/kg), or MEPH (15 mg/kg) were injected with METH after 10 days of drug absence. Cocaine challenge produced greater locomotor activity following pretreatment with cocaine or MEPH than following pretreatment with saline. METH challenge produced greater locomotor activity following METH pretreatment than following saline pretreatment; however, locomotor activity in rats pretreated with MEPH or saline and then challenged with METH was not significantly different. The locomotor response to MEPH (15 mg/kg) was not significantly affected by pretreatment with cocaine (15 mg/kg) or METH (0.5, 2 mg/kg). The present demonstration that cocaine-induced locomotor activation is enhanced by prior MEPH exposure suggests that MEPH cross-sensitizes to cocaine and increases cocaine efficacy. Interestingly, MEPH cross-sensitization was not bi-directional and did not extend to METH, suggesting the phenomenon is sensitive to specific psychostimulants. PMID:24126218

  14. Mephedrone interactions with cocaine: prior exposure to the 'bath salt' constituent enhances cocaine-induced locomotor activation in rats.

    Science.gov (United States)

    Gregg, Ryan A; Tallarida, Christopher S; Reitz, Allen B; Rawls, Scott M

    2013-12-01

    Concurrent use of mephedrone (4-methylmethcathinone; MEPH) and established drugs of abuse is now commonplace, but knowledge about interactions between these drugs is sparse. The present study was designed to test the hypothesis that prior MEPH exposure enhances the locomotor-stimulant effects of cocaine and methamphetamine (METH). For cocaine experiments, rats pretreated with saline, cocaine (15 mg/kg), or MEPH (15 mg/kg) for 5 days were injected with cocaine after 10 days of drug absence. For METH experiments, rats pretreated with saline, METH (2 mg/kg), or MEPH (15 mg/kg) were injected with METH after 10 days of drug absence. Cocaine challenge produced greater locomotor activity after pretreatment with cocaine or MEPH than after pretreatment with saline. METH challenge produced greater locomotor activity after METH pretreatment than after saline pretreatment; however, locomotor activity in rats pretreated with MEPH or saline and then challenged with METH was not significantly different. The locomotor response to MEPH (15 mg/kg) was not significantly affected by pretreatment with cocaine (15 mg/kg) or METH (0.5, 2 mg/kg). The present demonstration that cocaine-induced locomotor activation is enhanced by prior MEPH exposure suggests that MEPH cross-sensitizes to cocaine and increases cocaine efficacy. Interestingly, MEPH cross-sensitization was not bidirectional and did not extend to METH, suggesting that the phenomenon is sensitive to specific psychostimulants.

  15. Drug and alcohol task force

    Energy Technology Data Exchange (ETDEWEB)

    Gordey, T. [ConocoPhillips Canada Resources Corp., Calgary, AB (Canada); Sunstrum, M. [Enform, Calgary, AB (Canada)

    2006-07-01

    Worker absenteeism due to substance abuse costs the Alberta economy approximately $720 million a year. It is estimated that 20 per cent of all drivers in fatal crashes were using alcohol, and the use of cannabis and cocaine in Alberta has more than doubled over the last 15 years. In addition, 1 in 10 Alberta workers have reported using alcohol while at work and 4 per cent have reported using alcohol 4 hours prior to coming to work during the previous 12 months. In an effort to ensure appropriate health and safety for workers in the Canadian petroleum industry, 6 trade associations in the sector have joined together as the Enform Alcohol and Drug Initiative and are now working to develop a common approach to drug and alcohol guidelines and workplace rules. The task group will determine if existing policies and guidelines are sufficient to ensure a safe workplace and will consider standardizing the testing, application and rehabilitation of workers with respect to the use of drugs and alcohol. In the past, disciplinary actions have often been reversed because employers have not been consistent or did not follow established alcohol and drug policies or test to specific standards. Various work rules for inappropriate alcohol and drug use were reviewed, as well as education and communication strategies regarding policy content. Standards for testing criteria were discussed, as well as issues concerning duty-to-accommodate circumstances. An excerpt of concentration standards was presented. It was concluded that a matrix for companies to assess and determine safety sensitive positions is needed. refs., tabs., figs.

  16. Prenatal exercise research.

    Science.gov (United States)

    Field, Tiffany

    2012-06-01

    In this review of recent research on prenatal exercise, studies from several different countries suggest that only approximately 40% of pregnant women exercise, even though about 92% are encouraged by their physicians to exercise, albeit with some 69% of the women being advised to limit their exercise. A moderate exercise regime reputedly increases infant birthweight to within the normal range, but only if exercise is decreased in late pregnancy. Lower intensity exercise such as water aerobics has decreased low back pain more than land-based physical exercise. Heart rate and blood pressure have been lower following yoga than walking, and complications like pregnancy-induced hypertension with associated intrauterine growth retardation and prematurity have been less frequent following yoga. No studies could be found on tai chi with pregnant women even though balance and the risk of falling are great concerns during pregnancy, and tai chi is one of the most effective forms of exercise for balance. Potential underlying mechanisms for exercise effects are that stimulating pressure receptors during exercise increases vagal activity which, in turn, decreases cortisol, increases serotonin and decreases substance P, leading to decreased pain. Decreased cortisol is particularly important inasmuch as cortisol negatively affects immune function and is a significant predictor of prematurity. Larger, more controlled trials are needed before recommendations can be made about the type and amount of pregnancy exercise.

  17. Cocaine-Induced Endocannabinoid Mobilization in the Ventral Tegmental Area.

    Science.gov (United States)

    Wang, Huikun; Treadway, Tyler; Covey, Daniel P; Cheer, Joseph F; Lupica, Carl R

    2015-09-29

    Cocaine is a highly addictive drug that acts upon the brain's reward circuitry via the inhibition of monoamine uptake. Endogenous cannabinoids (eCB) are lipid molecules released from midbrain dopamine (DA) neurons that modulate cocaine's effects through poorly understood mechanisms. We find that cocaine stimulates release of the eCB, 2-arachidonoylglycerol (2-AG), in the rat ventral midbrain to suppress GABAergic inhibition of DA neurons, through activation of presynaptic cannabinoid CB1 receptors. Cocaine mobilizes 2-AG via inhibition of norepinephrine uptake and promotion of a cooperative interaction between Gq/11-coupled type-1 metabotropic glutamate and α1-adrenergic receptors to stimulate internal calcium stores and activate phospholipase C. The disinhibition of DA neurons by cocaine-mobilized 2-AG is also functionally relevant because it augments DA release in the nucleus accumbens in vivo. Our results identify a mechanism through which the eCB system can regulate the rewarding and addictive properties of cocaine.

  18. Cocaine is pharmacologically active in the nonhuman primate fetal brain

    DEFF Research Database (Denmark)

    Benveniste, Helene; Fowler, Joanna S; Rooney, William D

    2010-01-01

    Cocaine use during pregnancy is deleterious to the newborn child, in part via its disruption of placental blood flow. However, the extent to which cocaine can affect the function of the fetal primate brain is still an unresolved question. Here we used PET and MRI and show that in third......-trimester pregnant nonhuman primates, cocaine at doses typically used by drug abusers significantly increased brain glucose metabolism to the same extent in the mother as in the fetus (approximately 100%). Inasmuch as brain glucose metabolism is a sensitive marker of brain function, the current findings provide...... evidence that cocaine use by a pregnant mother will also affect the function of the fetal brain. We are also unique in showing that cocaine's effects in brain glucose metabolism differed in pregnant (increased) and nonpregnant (decreased) animals, which suggests that the psychoactive effects of cocaine...

  19. Cocaine treatment admissions at three sentinel sites in South Africa (1997-2006): findings and implications for policy, practice and research.

    Science.gov (United States)

    Parry, Charles D H; Plüddemann, Andreas; Myers, Bronwyn J

    2007-12-28

    Accurate prevalence data on cocaine use, that points to where problems exist and the extent of these problems, is necessary to guide the formulation of effective substance abuse policy and practice. The purpose of this study was to provide surveillance information about the nature and extent of problematic cocaine use in South Africa. Data were collected between January 1997 and December 2006 on admissions for drug abuse treatment through a regular monitoring system involving 56 drug treatment centres and programmes in Cape Town, Gauteng Province (Johannesburg and Pretoria) and the Eastern Cape every six months as part of the South African Community Epidemiology Network on Drug Use (SACENDU). A one-page form was completed by treatment centre personnel to obtain demographic data, the patients' primary and secondary substances of abuse, the mode, frequency and age of first use of substance, and information on prior treatment. Treatment indicators point to a significant increase in cocaine related admissions over time in all sites, but with substantial inter-site variation, particularly in recent years. The data indicate high levels of crack cocaine use and high levels of daily usage among patients, most of whom were first time admissions. Patients with cocaine related problems continue to be predominantly male, with a mean age of around 30 years. Substantial changes in the racial profile of patients have occurred over time. Poly drug use is high with cocaine often used with alcohol, cannabis and other drugs. These trends point to the possibility of cocaine use becoming a serious health and social issue in South Africa and demonstrate the utility of continued monitoring of cocaine treatment admissions in the future. They also highlight the need to address cocaine use in national and provincial policy planning and intervention efforts. In terms of treatment, the findings highlight the need to ensure that treatment practitioners are adequately trained to address

  20. Cocaine treatment admissions at three sentinel sites in South Africa (1997–2006: findings and implications for policy, practice and research

    Directory of Open Access Journals (Sweden)

    Plüddemann Andreas

    2007-12-01

    Full Text Available Abstract Background Accurate prevalence data on cocaine use, that points to where problems exist and the extent of these problems, is necessary to guide the formulation of effective substance abuse policy and practice. The purpose of this study was to provide surveillance information about the nature and extent of problematic cocaine use in South Africa. Methods Data were collected between January 1997 and December 2006 on admissions for drug abuse treatment through a regular monitoring system involving 56 drug treatment centres and programmes in Cape Town, Gauteng Province (Johannesburg and Pretoria and the Eastern Cape every six months as part of the South African Community Epidemiology Network on Drug Use (SACENDU. A one-page form was completed by treatment centre personnel to obtain demographic data, the patients' primary and secondary substances of abuse, the mode, frequency and age of first use of substance, and information on prior treatment. Results Treatment indicators point to a significant increase in cocaine related admissions over time in all sites, but with substantial inter-site variation, particularly in recent years. The data indicate high levels of crack cocaine use and high levels of daily usage among patients, most of whom were first time admissions. Patients with cocaine related problems continue to be predominantly male, with a mean age of around 30 years. Substantial changes in the racial profile of patients have occurred over time. Poly drug use is high with cocaine often used with alcohol, cannabis and other drugs. Conclusion These trends point to the possibility of cocaine use becoming a serious health and social issue in South Africa and demonstrate the utility of continued monitoring of cocaine treatment admissions in the future. They also highlight the need to address cocaine use in national and provincial policy planning and intervention efforts. In terms of treatment, the findings highlight the need to ensure that

  1. Maternal alcohol consumption during pregnancy and semen quality in the male offspring: two decades of follow-up

    DEFF Research Database (Denmark)

    Ramlau-Hansen, Cecilia; Toft, G; Jensen, M S

    2010-01-01

    Concurrent alcohol exposure has been associated with reduced fecundity, but no studies have estimated the effect of prenatal alcohol exposure on male fecundity. The aim of this study was to investigate the association between maternal alcohol consumption during pregnancy, semen quality and levels...

  2. Prenatal substance exposure: What predicts behavioral resilience by early adolescence?

    Science.gov (United States)

    Liebschutz, Jane M; Crooks, Denise; Rose-Jacobs, Ruth; Cabral, Howard J; Heeren, Timothy C; Gerteis, Jessie; Appugliese, Danielle P; Heymann, Orlaith D; Lange, Allison V; Frank, Deborah A

    2015-06-01

    Understanding behavioral resilience among at-risk adolescents may guide public policy decisions and future programs. We examined factors predicting behavioral resilience following intrauterine substance exposure in a prospective longitudinal birth-cohort study of 136 early adolescents (ages 12.4-15.9 years) at risk for poor behavioral outcomes. We defined behavioral resilience as a composite measure of lack of early substance use initiation (before age 14), lack of risky sexual behavior, or lack of delinquency. Intrauterine substance exposures included in this analysis were cocaine, tobacco, alcohol, and marijuana. We recruited participants from Boston Medical Center as mother-infant dyads between 1990 and 1993. The majority of the sample was African American/Caribbean (88%) and 49% female. In bivariate analyses, none and lower intrauterine cocaine exposure level predicted resilience compared with higher cocaine exposure, but this effect was not found in an adjusted model. Instead, strict caregiver supervision (adjusted odds ratio [AOR] = 6.02, 95% confidence interval (CI) [1.90, 19.00], p = .002), lower violence exposure (AOR = 4.07, 95% CI [1.77, 9.38], p < .001), and absence of intrauterine tobacco exposure (AOR = 3.71, 95% CI [1.28, 10.74], p = .02) predicted behavioral resilience. In conclusion, caregiver supervision in early adolescence, lower violence exposure in childhood, and lack of intrauterine tobacco exposure predicted behavioral resilience among a cohort of early adolescents with significant social and environmental risk. Future interventions should work to enhance parental supervision as a way to mitigate the effects of adversity on high-risk groups of adolescents. (PsycINFO Database Record

  3. Prenatal Testing: Is It Right for You?

    Science.gov (United States)

    Healthy Lifestyle Pregnancy week by week Prenatal testing, including screening and diagnostic tests, can provide valuable information about your baby's ... 2015 Original article: http://www.mayoclinic.org/healthy-lifestyle/pregnancy-week-by-week/in-depth/prenatal-testing/art- ...

  4. The impact of orbitofrontal dysfunction on cocaine addiction

    OpenAIRE

    Lucantonio, Federica; Stalnaker, Thomas A; Shaham, Yavin; Niv, Yael; Schoenbaum, Geoffrey

    2012-01-01

    Cocaine addiction is characterized by poor judgment and maladaptive decision-making. Here we review evidence implicating the orbitofrontal cortex in such behavior. This evidence suggests that cocaine-induced changes in orbitofrontal cortex disrupt the representation of states and transition functions that form the basis of flexible and adaptive ‘model-based’ behavioral control. By impairing this function, cocaine exposure leads to an overemphasis on less flexible, maladaptive ‘model-free’ con...

  5. Quality of life and sleep impairment in chronic cocaine dependents

    OpenAIRE

    Lima,Adriana; ROSSINI, Sueli; Reimão,Rubens

    2008-01-01

    OBJECTIVE: To evaluate quality of life (QL) and sleep quality impairment of cocaine chronic dependents in use of cocaine. METHOD: 40 patients, chronic cocaine dependents were evaluated (37 M; 3 F), with mean age of 28.92 years, along with 40 controls paired for gender and age. The following instruments were used: a) the semi-structured clinical interview; b) the Brazil Economic Classification; c) the Pittsburgh Sleep Quality Index; d) World Heath Organization Quality of Life-BREF (WHOQOL-BREF...

  6. Neurodevelopmental Outcomes of Prenatal Stress

    Directory of Open Access Journals (Sweden)

    M. Genco Usta

    2012-03-01

    Full Text Available The influence of prenatal stress on psychopathology has been observed in many animal and human studies. In many studies, stress during prenatal period has been shown to result in negative feedback dysregulation and hyperactivity of hypothalamo-pituitary-adrenocortical axis. Prenatal stres also may cause increased risk of birth complications, startle or distress in response to novel and surprising stimuli during infancy; lower Full Scale IQs, language abilities and attention deficiency in period of 3-5 years; increased risk of attention deficit hyperactivity syndrome, anxiety symptoms, depressive disorder and impulsivity during adolescence. Additionally, timing of prenatal stress is also important and 12-22 weeks of gestation seems to be the most vulnerable period. The results underline the need for early prevention and intervention programs for highly anxious women during pregnancy. Administration of prenatal stress monitoring to public health programs or removing pregnant women who have been exposed to life events such as natural disaster, terror attack to secure areas that provide basic needs may be crucial.

  7. The impact of orbitofrontal dysfunction on cocaine addiction.

    Science.gov (United States)

    Lucantonio, Federica; Stalnaker, Thomas A; Shaham, Yavin; Niv, Yael; Schoenbaum, Geoffrey

    2012-01-22

    Cocaine addiction is characterized by poor judgment and maladaptive decision-making. Here we review evidence implicating the orbitofrontal cortex in such behavior. This evidence suggests that cocaine-induced changes in orbitofrontal cortex disrupt the representation of states and transition functions that form the basis of flexible and adaptive 'model-based' behavioral control. By impairing this function, cocaine exposure leads to an overemphasis on less flexible, maladaptive 'model-free' control systems. We propose that such an effect accounts for the complex pattern of maladaptive behaviors associated with cocaine addiction.

  8. Optogenetic Central Amygdala Stimulation Intensifies and Narrows Motivation for Cocaine.

    Science.gov (United States)

    Warlow, Shelley M; Robinson, Mike J F; Berridge, Kent C

    2017-08-30

    Addiction is often characterized by intense motivation for a drug, which may be narrowly focused at the expense of other rewards. Here, we examined the role of amygdala-related circuitry in the amplification and narrowing of motivation focus for intravenous cocaine. We paired optogenetic channelrhodopsin (ChR2) stimulation in either central nucleus of amygdala (CeA) or basolateral amygdala (BLA) of female rats with one particular nose-poke porthole option for earning cocaine infusions (0.3 mg/kg, i.v.). A second alternative porthole earned identical cocaine but without ChR2 stimulation. Consequently, CeA rats quickly came to pursue their CeA ChR2-paired cocaine option intensely and exclusively, elevating cocaine intake while ignoring their alternative cocaine alone option. By comparison, BLA ChR2 pairing failed to enhance cocaine motivation. CeA rats also emitted consummatory bites toward their laser-paired porthole, suggesting that higher incentive salience made that cue more attractive. A separate progressive ratio test of incentive motivation confirmed that CeA ChR2 amplified rats' motivation, raising their breakpoint effort price for cocaine by 10-fold. However, CeA ChR2 laser on its own lacked any reinforcement value: laser by itself was never self-stimulated, not even by the same rats in which it amplified motivation for cocaine. Conversely, CeA inhibition by muscimol/baclofen microinjections prevented acquisition of cocaine self-administration and laser preference, whereas CeA inhibition by optogenetic halorhodopsin suppressed cocaine intake, indicating that CeA circuitry is needed for ordinary cocaine motivation. We conclude that CeA ChR2 excitation paired with a cocaine option specifically focuses and amplifies motivation to produce intense pursuit and consumption focused on that single target.SIGNIFICANCE STATEMENT In addiction, intense incentive motivation often becomes narrowly focused on a particular drug of abuse. Here we show that pairing central

  9. Cannabidiol Rescues Acute Hepatic Toxicity and Seizure Induced by Cocaine

    Directory of Open Access Journals (Sweden)

    Luciano Rezende Vilela

    2015-01-01

    Full Text Available Cocaine is a commonly abused illicit drug that causes significant morbidity and mortality. The most severe and common complications are seizures, ischemic strokes, myocardial infarction, and acute liver injury. Here, we demonstrated that acute cocaine intoxication promoted seizure along with acute liver damage in mice, with intense inflammatory infiltrate. Considering the protective role of the endocannabinoid system against cell toxicity, we hypothesized that treatment with an anandamide hydrolysis inhibitor, URB597, or with a phytocannabinoid, cannabidiol (CBD, protects against cocaine toxicity. URB597 (1.0 mg/kg abolished cocaine-induced seizure, yet it did not protect against acute liver injury. Using confocal liver intravital microscopy, we observed that CBD (30 mg/kg reduced acute liver inflammation and damage induced by cocaine and prevented associated seizure. Additionally, we showed that previous liver damage induced by another hepatotoxic drug (acetaminophen increased seizure and lethality induced by cocaine intoxication, linking hepatotoxicity to seizure dynamics. These findings suggest that activation of cannabinoid system may have protective actions on both liver and brain induced by cocaine, minimizing inflammatory injury promoted by cocaine, supporting its further clinical application in the treatment of cocaine abuse.

  10. Affinity for risky behaviors following prenatal and early childhood exposure to tetrachloroethylene (PCE-contaminated drinking water: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Aschengrau Ann

    2011-12-01

    Full Text Available Abstract Background Many studies of adults with acute and chronic solvent exposure have shown adverse effects on cognition, behavior and mood. No prior study has investigated the long-term impact of prenatal and early childhood exposure to the solvent tetrachloroethylene (PCE on the affinity for risky behaviors, defined as smoking, drinking or drug use as a teen or adult. Objectives This retrospective cohort study examined whether early life exposure to PCE-contaminated drinking water influenced the occurrence of cigarette smoking, alcohol consumption, and drug use among adults from Cape Cod, Massachusetts. Methods Eight hundred and thirty-one subjects with prenatal and early childhood PCE exposure and 547 unexposed subjects were studied. Participants completed questionnaires to gather information on risky behaviors as a teenager and young adult, demographic characteristics, other sources of solvent exposure, and residences from birth through 1990. PCE exposure was estimated using the U.S. EPA's water distribution system modeling software (EPANET that was modified to incorporate a leaching and transport model to estimate PCE exposures from pipe linings. Results Individuals who were highly exposed to PCE-contaminated drinking water during gestation and early childhood experienced 50-60% increases in the risk of using two or more major illicit drugs as a teenager or as an adult (Relative Risk (RR for teen use = 1.6, 95% CI: 1.2-2.2; and RR for adult use = 1.5, 95% CI: 1.2-1.9. Specific drugs for which increased risks were observed included crack/cocaine, psychedelics/hallucinogens, club/designer drugs, Ritalin without a prescription, and heroin (RRs:1.4-2.1. Thirty to 60% increases in the risk of certain smoking and drinking behaviors were also seen among highly exposed subjects. Conclusions The results of this study suggest that risky behaviors, particularly drug use, are more frequent among adults with high PCE exposure levels during gestation

  11. National Institute on Alcohol Abuse and Alcoholism

    Science.gov (United States)

    Skip to main content National Institute on Alcohol Abuse and Alcoholism (NIAAA) Main Menu Search Search form Search Alcohol & Your Health Overview of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use ...

  12. Update on prenatal care.

    Science.gov (United States)

    Zolotor, Adam J; Carlough, Martha C

    2014-02-01

    Many elements of routine prenatal care are based on tradition and lack a firm evidence base; however, some elements are supported by more rigorous studies. Correct dating of the pregnancy is critical to prevent unnecessary inductions and to allow for accurate treatment of preterm labor. Physicians should recommend folic acid supplementation to all women as early as possible, preferably before conception, to reduce the risk of neural tube defects. Administration of Rho(D) immune globulin markedly decreases the risk of alloimmunization in an RhD-negative woman carrying an RhD-positive fetus. Screening and treatment for iron deficiency anemia can reduce the risks of preterm labor, intrauterine growth retardation, and perinatal depression. Testing for aneuploidy and neural tube defects should be offered to all pregnant women with a discussion of the risks and benefits. Specific genetic testing should be based on the family histories of the patient and her partner. Physicians should recommend that pregnant women receive a vaccination for influenza, be screened for asymptomatic bacteriuria, and be tested for sexually transmitted infections. Testing for group B streptococcus should be performed between 35 and 37 weeks' gestation. If test results are positive or the patient has a history of group B streptococcus bacteriuria during pregnancy, intrapartum antibiotic prophylaxis should be administered to reduce the risk of infection in the infant. Intramuscular or vaginal progesterone should be considered in women with a history of spontaneous preterm labor, preterm premature rupture of membranes, or shortened cervical length (less than 2.5 cm). Screening for diabetes should be offered using a universal or a risk-based approach. Women at risk of preeclampsia should be offered low-dose aspirin prophylaxis, as well as calcium supplementation if dietary calcium intake is low. Induction of labor may be considered between 41 and 42 weeks' gestation.

  13. [Communication skills for prenatal counselling].

    Science.gov (United States)

    Bitzer, J; Tschudin, S; Holzgreve, W; Tercanli, S

    2007-04-18

    Prenatal counselling is characterized by specific characteristics: A):The communication is about the values of the pregnant woman and her relationship with the child to be. B) The communication deals with patient's images and emotions. C) It is a communication about risks, numbers and statistics. D) Physician and patient deal with important ethical issues. In this specific setting of prenatal diagnosis and care physicians should therefore learn to apply basic principles of patient-centred communication with elements of non directive counselling, patient education and shared decision making. These elements are integrated into a process which comprises the following "steps": 1. Clarification of the patient's objectives and the obstetrician's mandate. 2. The providing of individualized information and education about prenatal tests and investigations. 3. Shared decision making regarding tests and investigations 4. Eventually Breaking (bad, ambivalent) news. 5. Caring for patients with an affected child.

  14. Effects of phendimetrazine treatment on cocaine vs food choice and extended-access cocaine consumption in rhesus monkeys.

    Science.gov (United States)

    Banks, Matthew L; Blough, Bruce E; Fennell, Timothy R; Snyder, Rodney W; Negus, S Stevens

    2013-12-01

    There is currently no Food and Drug Administration-approved pharmacotherapy for cocaine addiction. Monoamine releasers such as d-amphetamine constitute one class of candidate medications, but clinical use and acceptance are hindered by their own high-abuse liability. Phendimetrazine (PDM) is a schedule III anorectic agent that functions as both a low-potency monoamine-uptake inhibitor and as a prodrug for the monoamine-releaser phenmetrazine (PM), and it may serve as a clinically available, effective, and safer alternative to d-amphetamine. This study determined efficacy of chronic PDM to reduce cocaine self-administration by rhesus monkeys (N=4) using a novel procedure that featured both daily assessments of cocaine vs food choice (to assess medication efficacy to reallocate behavior away from cocaine choice and toward choice of an alternative reinforcer) and 20 h/day cocaine access (to allow high-cocaine intake). Continuous 21-day treatment with ramping PDM doses (days 1-7: 0.32 mg/kg/h; days 8-21: 1.0 mg/kg/h) reduced cocaine choices, increased food choices, and nearly eliminated extended-access cocaine self-administration without affecting body weight. There was a trend for plasma PDM and PM levels to correlate with efficacy to decrease cocaine choice such that the monkey with the highest plasma PDM and PM levels also demonstrated the greatest reductions in cocaine choice. These results support further consideration of PDM as a candidate anti-cocaine addiction pharmacotherapy. Moreover, PDM may represent a novel pharmacotherapeutic approach for cocaine addiction because it may simultaneously function as both a monoamine-uptake inhibitor (via the parent drug PDM) and as a monoamine releaser (via the active metabolite PM).

  15. [Diagnosis of fetal alcohol spectrum disorders].

    Science.gov (United States)

    van Wieringen, Hester; Letteboer, Tom G W; Pereira, Rob Rodrigues; de Ruiter, Sanne; Balemans, Walter A F; Lindhout, Dick

    2010-01-01

    Prenatal alcohol exposure may cause decreased growth of the child, congenital abnormalities, specific facial characteristics, and, most importantly, mental retardation and behavioural disorders, all known as fetal alcohol spectrum disorders (FASD). A significant number of pregnant women in the Netherlands drink alcohol, but the prevalence of FASD in our country is unknown. Repeated and high peak blood alcohol concentrations, for example in the case of binge drinking by the mother, result in more severe abnormalities; a safe limit for alcohol consumption in pregnancy cannot be defined. In 2007 and 2008, Dutch paediatricians reported a total of 56 diagnosed cases of FASD, mostly adopted and foster children. Possibly the condition has not always been diagnosed. Use of international guidelines for diagnosis by the medical profession may improve detection. The guidelines of the Canadian Public Health Agency provide a useful and generally accepted classification, with strict cut-off points to avoid overdiagnosis; attention should always be paid to the broad differential diagnosis.

  16. CIA and the Contras' cocaine connection

    OpenAIRE

    Kain, Victor

    2006-01-01

    The evidence shows that the government knew that the Contras’ decided to traffic cocaine to finance themselves. The government participated in the drug trafficking by not interrupting it. CIA ordered the Contras to traffic drugs. Traffickers were protected from prosecution and received government contract. The government knew and sanctioned the drug trafficking into the US to support the Contras. The White House urged lenience for at least one convicted trafficker and terrorist.

  17. Controlling Cocaine. Supply Versus Demand Programs

    Science.gov (United States)

    1994-01-01

    ALERT (Ellickson and Bell, 1990a, 1990b; and Ellickson, Bell, and Harrison , 1993) indicate that school-based prevention programs do decrease drug use...Robert M. Bell, and Ellen R. Harrison (1993), "Changing Adolescent Propensities to Use Drugs: Results from Project ALERT," Health Education Quarterly, Vol...1988), "Cocaine and Other Stimulants: Actions, Abuse, and Treatment," New England Journal of MedicinA Vol. 318, No. 18, May, pp. 1173-1182. Gerstein

  18. Increased corticolimbic connectivity in cocaine dependence versus pathological gambling is associated with drug severity and emotion-related impulsivity.

    Science.gov (United States)

    Contreras-Rodríguez, Oren; Albein-Urios, Natalia; Vilar-López, Raquel; Perales, Jose C; Martínez-Gonzalez, Jose M; Fernández-Serrano, Maria J; Lozano-Rojas, Oscar; Clark, Luke; Verdejo-García, Antonio

    2016-05-01

    Neural biomarkers for the active detrimental effects of cocaine dependence (CD) are lacking. Direct comparisons of brain connectivity in cocaine-targeted networks between CD and behavioural addictions (i.e. pathological gambling, PG) may be informative. This study therefore contrasted the resting-state functional connectivity networks of 20 individuals with CD, 19 individuals with PG and 21 healthy individuals (controls). Study groups were assessed to rule out psychiatric co-morbidities (except alcohol abuse and nicotine dependence) and current substance use or gambling (except PG). We first examined global connectivity differences in the corticolimbic reward network and then utilized seed-based analyses to characterize the connectivity of regions displaying between-group differences. We examined the relationships between seed-based connectivity and trait impulsivity and cocaine severity. CD compared with PG displayed increased global functional connectivity in a large-scale ventral corticostriatal network involving the orbitofrontal cortex, caudate, thalamus and amygdala. Seed-based analyses showed that CD compared with PG exhibited enhanced connectivity between the orbitofrontal and subgenual cingulate cortices and between caudate and lateral prefrontal cortex, which are involved in representing the value of decision-making feedback. CD and PG compared with controls showed overlapping connectivity changes between the orbitofrontal and dorsomedial prefrontal cortices and between amygdala and insula, which are involved in stimulus-outcome learning. Orbitofrontal-subgenual cingulate cortical connectivity correlated with impulsivity and caudate/amygdala connectivity correlated with cocaine severity. We conclude that CD is linked to enhanced connectivity in a large-scale ventral corticostriatal-amygdala network that is relevant to decision making and likely to reflect an active cocaine detrimental effect.

  19. PRENATAL DIAGNOSIS IN ORGANIC ACIDEMIA

    Directory of Open Access Journals (Sweden)

    Hedieh SANEIFARD

    2012-03-01

    Full Text Available Organic acidemias are the group of metabolic disorders which define by high anion gap metabolic acidosis, hypo or hyperglycemia & hyperammonemia.Because of the severity of disease in children and its fatality in severe form of disease and also need for life long treatment, prenatal diagnosis is an important diagnostic tool.Three approaches to prenatal diagnosis may be possible, including measurement of analytes in amniotic fluid or use of cells obtained by Choronic Villus sampling (CVS or amniocentesis to either assay enzyme activity or extract DNA for molecular genetic testing.Biochemical genetic testing: Prenatal diagnosis for pregnancies at increased risk for propionic acidemia, methylmalonic acidemia, biotin-unresponsive3-methylcrotonyl-CoA carboxylase deficiency, glutaric acidemia type 1, ketothiolase deficiency, methylmalonic aciduria and homocystinuria, cblC type, and isovaleric acidemia is possible by analysis of amniotic fluid if highly accurate quantitative methods are used to measure the appropriate analytes. Amniocentesis is usually performed at approximately 15 to 18 weeks gestation.Prenatal diagnosis for pregnancies at increased risk for MSUD is possible by measurement of enzyme activity in fetal cells obtained by chorionic villous sampling(CVS at approximately ten to 12 weeks gestation or amniocentesis usually performed at approximately 15 to 18 weeks gestation.(If cells from CVS are used, extreme care must be taken to assure that they are fetal rather than maternal cells.Molecular genetic testing:Prenatal diagnosis for pregnancies at increased risk for all disorders is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis usually performed at approximately 15 to 18 weeks of gestation or chorionic villous sampling (CVS at approximately ten to 12 weeks of gestation. Both disease-causing allels of an affected family member must be identified before prenatal testing.Preimplantation genetic diagnosis (PGD

  20. Prenatal prediction of pulmonary hypoplasia.

    Science.gov (United States)

    Triebwasser, Jourdan E; Treadwell, Marjorie C

    2017-03-15

    Pulmonary hypoplasia, although rare, is associated with significant neonatal morbidity and mortality. Conditions associated with pulmonary hypoplasia include those which limit normal thoracic capacity or movement, including skeletal dysplasias and abdominal wall defects; those with mass effect, including congenital diaphragmatic hernia and pleural effusions; and those with decreased amniotic fluid, including preterm, premature rupture of membranes, and genitourinary anomalies. The ability to predict severe pulmonary hypoplasia prenatally aids in family counseling, as well as obstetric and neonatal management. The objective of this review is to outline the imaging techniques that are widely used prenatally to assess pulmonary hypoplasia and to discuss the limitations of these methods.

  1. Association of elevated ambient temperature with death from cocaine overdose.

    Science.gov (United States)

    Auger, Nathalie; Bilodeau-Bertrand, Marianne; Labesse, Maud Emmanuelle; Kosatsky, Tom

    2017-09-01

    Ecologic data suggest that elevated outdoor temperature is correlated with mortality rates from cocaine overdose. Using non-aggregated death records, we studied the association of hot temperatures with risk of death from cocaine overdose. We carried out a case-crossover study of all deaths from cocaine or other drug overdose between the months of May and September, from 2000 through 2013 in Quebec, Canada. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between maximum outdoor temperature and death from cocaine or other drug overdose. The main outcome measure was death from cocaine overdose as a function of maximum temperature the day of death and the days immediately preceding death. There were 316 deaths from cocaine overdose and 446 from other drug overdoses during the study. Elevated temperature the preceding week was associated with the likelihood of death from cocaine but not other drug overdose. Compared with 20°C, a maximum weekly temperature of 30°C was associated with an OR of 2.07 for death from cocaine overdose (95% CI 1.15-3.73), but an OR of 1.03 for other drug overdoses (95% CI 0.60-1.75). Associations for cocaine overdose were present with maximum daily temperature the day of and each of the three days preceding death. Elevated ambient temperature is associated with the risk of death from cocaine overdose. Public health practitioners and drug users should be aware of the added risk of mortality when cocaine is used during hot days. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Prenatal care effectiveness and utilization in Brazil.

    Science.gov (United States)

    Wehby, George L; Murray, Jeffrey C; Castilla, Eduardo E; Lopez-Camelo, Jorge S; Ohsfeldt, Robert L

    2009-05-01

    The impact of prenatal care use on birth outcomes has been understudied in South American countries. This study assessed the effects of various measures of prenatal care use on birth weight (BW) and gestational age outcomes using samples of infants born without and with common birth defects from Brazil, and evaluated the demand for prenatal care. Prenatal visits improved BW in the group without birth defects through increasing both fetal growth rate and gestational age, but prenatal care visits had an insignificant effect on BW in the group with birth defects when adjusting for gestational age. Prenatal care delay had no effects on BW in both infant groups but increased preterm birth risk in the group without birth defects. Inadequate care versus intermediate care also increased LBW risk in the group without birth effects. Quantile regression analyses revealed that prenatal care visits had larger effects at low compared with high BW quantiles. Several other prenatal factors and covariates such as multivitamin use and number of previous live births had significant effects on the studied outcomes. The number of prenatal care visits was significantly affected by several maternal health and fertility indicators. Significant geographic differences in utilization were observed as well. The study suggests that more frequent use of prenatal care can increase BW significantly in Brazil, especially among pregnancies that are uncomplicated with birth defects but that are at high risk for low birth weight. Further research is needed to understand the effects of prenatal care use for pregnancies that are complicated with birth defects.

  3. Cue-induced craving in patients with cocaine use disorder predicts cognitive control deficits toward cocaine cues.

    Science.gov (United States)

    DiGirolamo, Gregory J; Smelson, David; Guevremont, Nathan

    2015-08-01

    Cue-induced craving is a clinically important aspect of cocaine addiction influencing ongoing use and sobriety. However, little is known about the relationship between cue-induced craving and cognitive control toward cocaine cues. While studies suggest that cocaine users have an attentional bias toward cocaine cues, the present study extends this research by testing if cocaine use disorder patients (CDPs) can control their eye movements toward cocaine cues and whether their response varied by cue-induced craving intensity. Thirty CDPs underwent a cue exposure procedure to dichotomize them into high and low craving groups followed by a modified antisaccade task in which subjects were asked to control their eye movements toward either a cocaine or neutral drug cue by looking away from the suddenly presented cue. The relationship between breakdowns in cognitive control (as measured by eye errors) and cue-induced craving (changes in self-reported craving following cocaine cue exposure) was investigated. CDPs overall made significantly more errors toward cocaine cues compared to neutral cues, with higher cravers making significantly more errors than lower cravers even though they did not differ significantly in addiction severity, impulsivity, anxiety, or depression levels. Cue-induced craving was the only specific and significant predictor of subsequent errors toward cocaine cues. Cue-induced craving directly and specifically relates to breakdowns of cognitive control toward cocaine cues in CDPs, with higher cravers being more susceptible. Hence, it may be useful identifying high cravers and target treatment toward curbing craving to decrease the likelihood of a subsequent breakdown in control. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Prenatal meditation influences infant behaviors.

    Science.gov (United States)

    Chan, Ka Po

    2014-11-01

    Meditation is important in facilitating health. Pregnancy health has been shown to have significant consequences for infant behaviors. In view of limited studies on meditation and infant temperament, this study aims to explore the effects of prenatal meditation on these aspects. The conceptual framework was based on the postulation of positive relationships between prenatal meditation and infant health. A randomized control quantitative study was carried out at Obstetric Unit, Queen Elizabeth Hospital in Hong Kong. 64 pregnant Chinese women were recruited for intervention and 59 were for control. Outcome measures were cord blood cortisol, infant salivary cortisol, and Carey Infant Temperament Questionnaire. Cord blood cortisol level of babies was higher in the intervention group (pmeditation can influence fetal health. Carey Infant Temperament Questionnaire showed that the infants of intervention group have better temperament (pmeditation in relation to child health. Present study concludes the positive effects of prenatal meditation on infant behaviors and recommends that pregnancy care providers should provide prenatal meditation to pregnant women.

  5. Prenatal diagnosis of 47,XXX.

    Science.gov (United States)

    Khoury-Collado, Fady; Wehbeh, Ammar N; Fisher, Allan J; Bombard, Allan T; Weiner, Zeev

    2005-05-01

    We report 2 cases of 47,XXX that were diagnosed prenatally and were screened positive for trisomy 21 by biochemical and ultrasound markers. These cases underline the importance of discussing the sex chromosome abnormalities during the genetic counseling after an abnormal triple screen test or ultrasound examination.

  6. Prenatal diagnosis of congenital diseases

    NARCIS (Netherlands)

    M.F. Niermeijer (Martinus)

    1975-01-01

    textabstractPrenatal diagnosis of a number of congenital diseases is possible by amniocentesis in the 14th - 16th week of pregnancy and subsequent analysis of cultured amniotic fluid cells or amniotic fluid supernatant. Parents at risk for a child with a chromosomal disorder, an X-linked disease, a

  7. The fast and furious : Cocaine, amphetamines and harm reduction

    NARCIS (Netherlands)

    J-P.C. Grund (Jean-Paul); P. Coffin (Philip); M. Jauffret-Roustide (Marie); M. Dijkstra (Minke); D. de Bruin (Dick); P. Blanken (Peter)

    2010-01-01

    textabstractCocaine and amphetamines (‘stimulants’) are distinct central nervous system stimulants with similar effects (Pleuvry, 2009; Holman, 1994). Cocaine is a crystalline tropane alkaloid extracted from coca leaves. Amphetamines are a subclass of phenylethylamines with primarily stimulant effec

  8. [Rhabdomyolysis in acute cocaine poisoning. Presentation of 2 cases].

    LENUS (Irish Health Repository)

    Bernad, M

    1990-12-01

    Because the important increase of cocaine abuse and the frequent pathology associated, we present two cases of males who had a multiorganic failure cause by severe rabdomyolysis, renal failure with myoglobinuria and disseminated intravascular coagulation, after the cocaine consumption. In one case a pancreatitis associated was observed, this not being described before. Both cases are recovered.

  9. CRF1 receptor-deficiency increases cocaine reward.

    Science.gov (United States)

    Contarino, Angelo; Kitchener, Pierre; Vallée, Monique; Papaleo, Francesco; Piazza, Pier-Vincenzo

    2017-01-27

    Stimulant drugs produce reward but also activate stress-responsive systems. The corticotropin-releasing factor (CRF) and the related hypothalamus-pituitary-adrenal (HPA) axis stress-responsive systems are activated by stimulant drugs. However, their role in stimulant drug-induced reward remains poorly understood. Herein, we report that CRF1 receptor-deficient (CRF1-/-), but not wild-type, mice show conditioned place preference (CPP) responses to a relatively low cocaine dose (5 mg/kg, i.p.). Conversely, wild-type, but not CRF1-/-, mice display CPP responses to a relatively high cocaine dose (20 mg/kg, i.p.), indicating that CRF1 receptor-deficiency alters the rewarding effects of cocaine. Acute pharmacological antagonism of the CRF1 receptor by antalarmin also eliminates cocaine reward. Nevertheless, CRF1-/- mice display higher stereotypy responses to cocaine than wild-type mice. Despite the very low plasma corticosterone concentration, CRF1-/- mice show higher nuclear glucocorticoid receptor (GR) levels in the brain region of the hippocampus than wild-type mice. Full rescue of wild-type-like corticosterone and GR circadian rhythm and level in CRF1-/- mice by exogenous corticosterone does not affect CRF1 receptor-dependent cocaine reward but induces stereotypy responses to cocaine. These results indicate a critical role for the CRF1 receptor in cocaine reward, independently of the closely related HPA axis activity.

  10. On the atomic structure of cocaine in solution.

    Science.gov (United States)

    Johnston, Andrew J; Busch, Sebastian; Pardo, Luis Carlos; Callear, Samantha K; Biggin, Philip C; McLain, Sylvia E

    2016-01-14

    Cocaine is an amphiphilic drug which has the ability to cross the blood-brain barrier (BBB). Here, a combination of neutron diffraction and computation has been used to investigate the atomic scale structure of cocaine in aqueous solutions. Both the observed conformation and hydration of cocaine appear to contribute to its ability to cross hydrophobic layers afforded by the BBB, as the average conformation yields a structure which might allow cocaine to shield its hydrophilic regions from a lipophilic environment. Specifically, the carbonyl oxygens and amine group on cocaine, on average, form ∼5 bonds with the water molecules in the surrounding solvent, and the top 30% of water molecules within 4 Å of cocaine are localized in the cavity formed by an internal hydrogen bond within the cocaine molecule. This water mediated internal hydrogen bonding suggests a mechanism of interaction between cocaine and the BBB that negates the need for deprotonation prior to interaction with the lipophilic portions of this barrier. This finding also has important implications for understanding how neurologically active molecules are able to interact with both the blood stream and BBB and emphasizes the use of structural measurements in solution in order to understand important biological function.

  11. Cocaine's appetite for fat and the consequences on body weight.

    Science.gov (United States)

    Billing, Lawrence; Ersche, Karen D

    2015-03-01

    For many individuals in treatment for cocaine dependence, weight gain is a substantial problem during recovery. This weight gain causes significant distress and seems to increase the risk of relapse. The mechanisms underlying cocaine's effects on weight remain elusive. It is widely assumed that this weight gain reflects a metabolic or behavioural compensatory response to the cessation of cocaine use. Here we challenge this assumption and outline potential mechanisms by which chronic cocaine use produces disturbances in the regulation of fat intake and storage, through its effects on the central and peripheral nervous systems, specifically the sympathetic nervous system. We hypothesize that the cocaine-induced alteration in fat regulation results in cocaine users developing a pronounced appetite for fatty food but keeps their fat mass low. This altered fat appetite subsequently leads to excessive weight gain when individuals enter treatment and stop using cocaine. Our aim is to shed light on the neurobiological mechanisms that may underlie the alterations in eating and fat regulation in cocaine-dependent individuals, to open up potential new avenues to support these individuals in recovery.

  12. Cannabis, Cocaine and the Wages of Prime Age Males

    NARCIS (Netherlands)

    van Ours, J.C.

    2005-01-01

    This paper uses a dataset collected among inhabitants of Amsterdam, to study whether wages of prime age male workers are affected by the use of cannabis and cocaine.The analysis shows that cocaine use and infrequent cannabis use do not affect wages.Frequent cannabis use has a negative wage effect.Th

  13. New Mexico women with no prenatal care: reasons, outcomes, and nursing implications.

    Science.gov (United States)

    Higgins, P G; Burton, M

    1996-01-01

    A retrospective chart review was conducted to determine why women received no prenatal care during pregnancy and their subsequent maternal and neonatal outcomes. Five hundred and eighty medical records from 1990 through 1993 that were labeled as no care were reviewed. Actually, only 270 records had no care and of these, 92 had 156 recorded reasons as to why women did not receive prenatal care. These reasons were categorized into three types of barriers: attitudinal, sociodemographic, and system-related. The majority of the women were young, Hispanic, unmarried, between 20 and 29 years of age, and uninsured, and had one to three children. Overall, the women did not smoke cigarettes, drink alcohol, or use drugs during pregnancy. Overall, the women had good maternal and newborn outcomes. Results suggest a need to reevaluate the effect of prenatal care use on young Hispanic women.

  14. Attitudes of young adults to prenatal screening and genetic correction for human attributes and psychiatric conditions.

    Science.gov (United States)

    Milner, K K; Collins, E E; Connors, G R; Petty, E M

    1998-03-05

    With recent advances in DNA technology, questions have arisen as to how this technology should be appropriately used. In this article, results obtained from a survey designed to elicit attitudes of college students to prenatal testing and gene therapy for human attributes and psychiatric conditions are reported. The eleven hypothetical disease phenotypes included schizophrenia, alcoholism, tendency toward violent behavior, attention deficit/hyperactivity disorder, depression requiring medical treatment, obesity, involvement in "dangerous" sports activities, homosexuality, borderline normal IQ (80-100), proportional short stature, and inability to detect perfect pitch. Most students supported prenatal genetic testing for psychiatric disorders and behavior that might result in harm to others (i.e., tendency towards violent behavior) and found prenatal genetic testing for human attributes less desirable. However, the lack of unilateral agreement or disagreement toward any one condition or attribute suggests the potential difficulties ahead in the quest for guidelines for the application of new technologies available to manipulate the human genome.

  15. Inactivation of the central nucleus of the amygdala reduces the effect of punishment on cocaine self-administration in rats

    OpenAIRE

    Xue, YueQiang; Steketee, Jeffery D.; Sun, Wenlin

    2012-01-01

    Continued cocaine use despite the negative consequences is a hallmark of cocaine addiction. One such consequence is punishment that is often used by society to curb cocaine use. Unfortunately, we know little about the mechanism involved in regulation by punishment of cocaine use. The fact that cocaine addicts continue cocaine use despite potential severe punishment suggests that the mechanism may be impaired. Such impairment is expected to critically contribute to compulsive cocaine use. This...

  16. Preclinical Assessment of Lisdexamfetamine as an Agonist Medication Candidate for Cocaine Addiction: Effects in Rhesus Monkeys Trained to Discriminate Cocaine or to Self-Administer Cocaine in a Cocaine Versus Food Choice Procedure.

    Science.gov (United States)

    Banks, Matthew L; Hutsell, Blake A; Blough, Bruce E; Poklis, Justin L; Negus, S Stevens

    2015-01-24

    Chronic amphetamine treatment decreases cocaine consumption in preclinical and human laboratory studies and in clinical trials. Lisdexamfetamine is an amphetamine prodrug in which L-lysine is conjugated to the terminal nitrogen of d-amphetamine. Prodrugs may be advantageous relative to their active metabolites due to slower onsets and longer durations of action; however, lisdexamfetamine treatment's efficacy in decreasing cocaine consumption is unknown. This study compared lisdexamfetamine and d-amphetamine effects in rhesus monkeys using two behavioral procedures: (1) a cocaine discrimination procedure (training dose = 0.32mg/kg cocaine, i.m.); and (2) a cocaine-versus-food choice self-administration procedure. In the cocaine-discrimination procedure, lisdexamfetamine (0.32-3.2mg/kg, i.m.) substituted for cocaine with lower potency, slower onset, and longer duration of action than d-amphetamine (0.032-0.32mg/kg, i.m.). Consistent with the function of lisdexamfetamine as an inactive prodrug for amphetamine, the time course of lisdexamfetamine effects was related to d-amphetamine plasma levels by a counter-clockwise hysteresis loop. In the choice procedure, cocaine (0-0.1mg/kg/injection, i.v.) and food (1g banana-flavored pellets) were concurrently available, and cocaine maintained a dose-dependent increase in cocaine choice under baseline conditions. Treatment for 7 consecutive days with lisdexamfetamine (0.32-3.2mg/kg/day, i.m.) or d-amphetamine (0.032-0.1mg/kg/h, i.v.) produced similar dose-dependent rightward shifts in cocaine dose-effect curves and decreases in preference for 0.032mg/kg/injection cocaine. Lisdexamfetamine has a slower onset and longer duration of action than amphetamine but retains amphetamine's efficacy to reduce the choice of cocaine in rhesus monkeys. These results support further consideration of lisdexamfetamine as an agonist-based medication candidate for cocaine addiction. © The Author 2015. Published by Oxford University Press on

  17. Disrupted Functional Connectivity with Dopaminergic Midbrain in Cocaine Abusers

    Energy Technology Data Exchange (ETDEWEB)

    Tomasi, D.; Tomasi, D.; Volkow, N.D.; Wang, R.; Carrillo, J.; Maloney, T.; Alia-Klein, N.; Woicik, P.A.; Telang, F.; Goldstein, R.Z.

    2010-06-01

    Chronic cocaine use is associated with disrupted dopaminergic neurotransmission but how this disruption affects overall brain function (other than reward/motivation) is yet to be fully investigated. Here we test the hypothesis that cocaine addicted subjects will have disrupted functional connectivity between the midbrain (where dopamine neurons are located) and cortical and subcortical brain regions during the performance of a sustained attention task. We measured brain activation and functional connectivity with fMRI in 20 cocaine abusers and 20 matched controls. When compared to controls, cocaine abusers had lower positive functional connectivity of midbrain with thalamus, cerebellum, and rostral cingulate, and this was associated with decreased activation in thalamus and cerebellum and enhanced deactivation in rostral cingulate. These findings suggest that decreased functional connectivity of the midbrain interferes with the activation and deactivation signals associated with sustained attention in cocaine addicts.

  18. Euglycemic Diabetic Ketoacidosis in a Patient with Cocaine Intoxication.

    Science.gov (United States)

    Abu-Abed Abdin, Asma; Hamza, Muhammad; Khan, Muhammad S; Ahmed, Awab

    2016-01-01

    Diabetic ketoacidosis (DKA) is characterized by elevated anion gap metabolic acidosis, hyperglycemia, and elevated ketones in urine and blood. Hyperglycemia is a key component of DKA; however, a subset of DKA patients can present with near-normal blood glucose, an entity described as "euglycemic DKA." This rare phenomenon is thought to be due to starvation and food restriction in insulin dependent diabetic patients. Cocaine abuse is considered a trigger for development of DKA. Cocaine also has anorexic effects. We describe an interesting case of euglycemic DKA in a middle-aged diabetic female presenting with elevated anion gap metabolic acidosis, with near-normal blood glucose, in the settings of noncompliance to insulin and cocaine abuse. We have postulated that cocaine abuse was implicated in the pathophysiology of euglycemic DKA in this case. This case highlights complex physiological interplay between type-1 diabetes, noncompliance to insulin, and cocaine abuse leading to DKA, with starvation physiology causing development of euglycemic DKA.

  19. Cocaine is pharmacologically active in the nonhuman primate fetal brain

    DEFF Research Database (Denmark)

    Benveniste, Helene; Fowler, Joanna S; Rooney, William D

    2010-01-01

    Cocaine use during pregnancy is deleterious to the newborn child, in part via its disruption of placental blood flow. However, the extent to which cocaine can affect the function of the fetal primate brain is still an unresolved question. Here we used PET and MRI and show that in third-trimester ......Cocaine use during pregnancy is deleterious to the newborn child, in part via its disruption of placental blood flow. However, the extent to which cocaine can affect the function of the fetal primate brain is still an unresolved question. Here we used PET and MRI and show that in third......-trimester pregnant nonhuman primates, cocaine at doses typically used by drug abusers significantly increased brain glucose metabolism to the same extent in the mother as in the fetus (approximately 100%). Inasmuch as brain glucose metabolism is a sensitive marker of brain function, the current findings provide...

  20. Cocaine-induced psychotic disorders: presentation, mechanism, and management.

    Science.gov (United States)

    Tang, Yilang; Martin, Nancy L; Cotes, Robert O

    2014-01-01

    Cocaine, the third mostly commonly used illicit drug in the United States, has a wide range of neuropsychiatric effects, including transient psychotic symptoms. When psychotic symptoms occur within a month of cocaine intoxication or withdrawal, the diagnosis is cocaine-induced psychotic disorder (CIPD). Current evidence suggests those with CIPD are likely to be male, have longer severity and duration of cocaine use, use intravenous cocaine, and have a lower body mass index. Differentiating CIPD from a primary psychotic disorder requires a detailed history of psychotic symptoms in relation to substance use and often a longitudinal assessment. Treatment includes providing a safe environment, managing agitation and psychosis, and addressing the underlying substance use disorder. This review begins with a clinical case and summarizes the literature on CIPD, including clinical presentation, differential diagnosis, mechanism and predictors of illness, and treatment.

  1. Low startle magnitude may be a behavioral marker of vulnerability to cocaine addiction.

    Science.gov (United States)

    Wheeler, Marina G; Duncan, Erica; Davis, Michael

    2017-01-01

    Cocaine addicted men have low startle magnitude persisting during prolonged abstinence. Low startle rats show greater cocaine self-administration than high startle rats. Low startle may be a marker of a vulnerability to heightened cocaine-related behaviors in rats and similarly may be a marker of vulnerability to cocaine addiction in humans.

  2. Activation of mGluR7s inhibits cocaine-induced reinstatement of drug-seeking behavior by a nucleus accumbens glutamate-mGluR2/3 mechanism in rats.

    Science.gov (United States)

    Li, Xia; Li, Jie; Gardner, Eliot L; Xi, Zheng-Xiong

    2010-09-01

    The metabotropic glutamate receptor 7 (mGluR7) has been reported to be involved in cocaine and alcohol self-administration. However, the role of mGluR7 in relapse to drug seeking is unknown. Using a rat relapse model, we found that systemic administration of AMN082, a selective mGluR7 allosteric agonist, dose-dependently inhibits cocaine-induced reinstatement of drug-seeking behavior. Intracranial microinjections of AMN082 into the nucleus accumbens (NAc) or ventral pallidum, but not the dorsal striatum, also inhibited cocaine-primed reinstatement, an effect that was blocked by local co-administration of MMPIP, a selective mGluR7 antagonist. In vivo microdialysis demonstrated that cocaine priming significantly increased extracellular dopamine in the NAc, ventral pallidum and dorsal striatum, while increasing extracellular glutamate in the NAc only. AMN082 alone failed to alter extracellular dopamine, but produced a slow-onset long-lasting increase in extracellular glutamate in the NAc only. Pre-treatment with AMN082 dose-dependently blocked both cocaine-enhanced NAc glutamate and cocaine-induced reinstatement, an effect that was blocked by MMPIP or LY341497 (a selective mGluR2/3 antagonist). These data suggest that mGluR7 activation inhibits cocaine-induced reinstatement of drug-seeking behavior by a glutamate-mGluR2/3 mechanism in the NAc. The present findings support the potential use of mGluR7 agonists for the treatment of cocaine addiction.

  3. Alcohol Abuse

    Science.gov (United States)

    ... even small amounts of alcohol may hurt an unborn child)Drink alcohol while you are looking after ... shakes, being very suspicious), and can even include death. This is why you need your doctor’s care ...

  4. A School Curriculum for Fetal Alcohol Spectrum Disorder: Advice from a Young Adult with FASD

    Science.gov (United States)

    Brenna, Beverley; Burles, Meridith; Holtslander, Lorraine; Bocking, Sarah

    2017-01-01

    While a significant number of individuals in Canada and globally are affected by prenatal fetal alcohol exposure, scant research exists that focuses specifically on the subjective experiences of this population. Based on a single case study exploring through Photovoice methodology the life experiences of a young adult with Fetal Alcohol Spectrum…

  5. A Dual-Focus Motivational Intervention to Reduce the Risk of Alcohol-Exposed Pregnancy

    Science.gov (United States)

    Velasquez, Mary M.; Ingersoll, Karen S.; Sobell, Mark B.; Floyd, R. Louise; Sobell, Linda Carter; von Sternberg, Kirk

    2010-01-01

    Project CHOICES developed an integrated behavioral intervention for prevention of prenatal alcohol exposure in women at high risk for alcohol-exposed pregnancies. Settings included primary care, university-hospital based obstetrical/gynecology practices, an urban jail, substance abuse treatment settings, and a media-recruited sample in three large…

  6. Evidence-Based Practice Guidelines for Fetal Alcohol Spectrum Disorder and Literacy and Learning

    Science.gov (United States)

    Mitten, H. Rae

    2013-01-01

    Evidence-based Practice Guidelines for Fetal Alcohol Spectrum Disorder (FASD) and Literacy and Learning are derived from an inductive analysis of qualitative data collected in field research. FASD is the umbrella term for a spectrum of neurocognitive and physical disabilities caused by prenatal exposure to alcohol. Data from a sample of N =150 was…

  7. Canadian Children and Youth in Care: The Cost of Fetal Alcohol Spectrum Disorder

    Science.gov (United States)

    Popova, Svetlana; Lange, Shannon; Burd, Larry; Rehm, Jürgen

    2014-01-01

    Background: A high prevalence of prenatal alcohol exposure has been reported among children in care and thus, the risk of fetal alcohol spectrum disorder (FASD) in this population is high. Objective: The purpose of the current study was to estimate the number of children (0-18 years) in care with FASD and to determine the associated cost by age…

  8. Reactivity to laboratory stress provocation predicts relapse to cocaine.

    Science.gov (United States)

    Back, Sudie E; Hartwell, Karen; DeSantis, Stacia M; Saladin, Michael; McRae-Clark, Aimee L; Price, Kimber L; Moran-Santa Maria, Megan M; Baker, Nathaniel L; Spratt, Eve; Kreek, Mary Jeanne; Brady, Kathleen T

    2010-01-01

    Cocaine dependence is a chronic relapsing disorder characterized by periods of abstinence and high rates of return to drug using behavior. Elevated levels of stress have been associated with relapse to cocaine; however, the nature of this association is not well understood. The relationship between reactivity to three human laboratory provocations and relapse to cocaine was investigated. Participants were 53 cocaine-dependent individuals who were admitted for a 2-day inpatient stay during which a psychosocial provocation (i.e., the Trier Social Stress Task), a pharmacological provocation (i.e., administration of 1 microg/kg corticotrophin releasing hormone; CRH), and a drug cue exposure paradigm were completed. Adrenocortico-trophic hormone (ACTH), cortisol, heart rate, and subjective cocaine craving and stress were assessed at baseline and at multiple time points post-task. Participants' cocaine use was monitored for approximately 1 month following testing. The majority (72.3%) of participants relapsed to cocaine during the follow-up period. In response to the CRH and drug cue exposure, elevated subjective craving and stress were significant predictors of cocaine use during follow-up. In response to the Trier, attenuated neuroendocrine responses were significant predictors of cocaine use. The findings provide further evidence of the ability of laboratory paradigms to predict relapse. The observed associations between stress reactivity and subsequent cocaine use highlight the clinical importance of the findings. Predictors of relapse may vary based on the type of provocation utilized. Interventions aimed at normalizing stress response, as measured using laboratory paradigms, may prove useful in relapse prevention. Published by Elsevier Ireland Ltd.

  9. Genome-Environmental Risk Assessment of Cocaine Dependence

    Directory of Open Access Journals (Sweden)

    Changshuai eWei

    2012-05-01

    Full Text Available Cocaine-associated biomedical and psychosocial problems are substantial 21st century global burdens of disease. This burden is largely driven by a cocaine dependence process that becomes engaged with increasing occasions of cocaine product use. For this reason, the development of a risk prediction model for cocaine dependence may be of special value. Ultimately, success in building such a risk prediction model may help promote personalized cocaine dependence prediction, prevention, and treatment approaches not presently available. As an initial step toward this goal, we conducted a genome-environmental risk prediction study for cocaine dependence, simultaneously considering 948,658 single nucleotide polymorphisms (SNPs, six potentially cocaine-related facets of environment, and three personal characteristics. In this study, a novel statistical approach was applied to 1045 case-control samples from the Family Study of Cocaine Dependence. The results identify 330 low- to medium-effect size SNPs (i.e., those with a single locus p-value of less than 10-4 that made a substantial contribution to cocaine dependence risk prediction (AUC=0.718. Inclusion of six facets of environment and three personal characteristics yielded greater accuracy (AUC=0.809. Of special importance was childhood abuse (CA among trauma experiences, with a potentially important interaction of CA and the GBE1 gene in cocaine dependence risk prediction. Genome-environmental risk prediction models may become more promising in future risk prediction research, once a more substantial array of environmental facets are taken into account, sometimes with model improvement when gene-by-environment product terms are included as part of these risk predication models.

  10. Opponent process properties of self-administered cocaine.

    Science.gov (United States)

    Ettenberg, Aaron

    2004-01-01

    Over the past decade, data collected in our laboratory have demonstrated that self-administered cocaine produces Opponent-Process-like behavioral effects. Animals running a straight alley once each day for IV cocaine develop over trials an approach-avoidance conflict about re-entering the goal box. This conflict behavior is characterized by a stop in forward locomotion (usually at the very mouth of the goal box) followed by a turn and 'retreat' back toward the goal box. The results of a series of studies conducted over the past decade collectively suggest that the behavioral ambivalence exemplified by rats running the alley for IV cocaine stems from concurrent and opponent positive (rewarding) and negative (anxiogenic) properties of the drug--both of which are associated with the goal box. These opponent properties of cocaine have been shown to result from temporally distinct affective states. Using a conditioned place preference test, we have been able to demonstrate that while the initial immediate effects of IV cocaine are reinforcing, the state present 15 min post-injection is aversive. In our most recent work, the co-administration of IV cocaine with either oral ethanol or IV heroin was found to greatly diminish the development and occurrence of retreat behaviors in the runway. It may therefore be that the high incidence of co-abuse of cocaine with either ethanol or heroin, stems from the users' motivation to alleviate some of the negative side effects of cocaine. It would seem then that the Opponent Process Theory has provided a useful conceptual framework for the study of the behavioral consequences of self-administered cocaine including the notion that both positive and negative reinforcement mechanisms are involved in the development and maintenance of cocaine abuse.

  11. Enhanced regional brain metabolic responses to benzodiazepines in cocaine abusers

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Wang, G.J.; Fowler, J.S. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1997-05-01

    While dopamine (DA) appears to be crucial for cocaine reinforcement, its involvement in cocaine addiction is much less clear. Using PET we have shown persistent reductions in striatal DA D2 receptors (which arc predominantly located on GABA cells) in cocaine abusers. This finding coupled to GABA`s role as an effector for DA led us to investigate if there were GABAergic abnormalities in cocaine abusers. In this study we measured regional brain metabolic responses to lorazepam, to indirectly assess GABA function (benzodiazepines facilitate GABAergic neurotransmission). Methods: The experimental subjects consisted of 12 active cocaine abusers and 32 age matched controls. Each subject underwent two PET FDG scans obtained within 1 week of each other. The first FDG scan was obtained after administration of placebo (3 cc of saline solution) given 40-50 minutes prior to FDG; and the second after administration of lorazepam (30 {mu}g/kg) given 40-50 minutes prior to FDG. The subjects were blind to the drugs received. Results: Lorazepam-induced sleepiness was significantly greater in abusers than in controls (p<0.001). Lorazepam-induced decreases in brain glucose metabolism were significantly larger in cocaine abusers than in controls. Whereas in controls whole brain metabolism decreased 13{+-}7 %, in cocaine abusers it decreased 21{+-}13 % (p < 0.05). Lorazepam-induced decrements in regional metabolism were significantly larger in striatum (p < 0.0 1), thalamus (p < 0.01) and cerebellum (p < 0.005) of cocaine abusers than of controls (ANOVA diagnosis by condition (placebo versus lorazepam) interaction effect). The only brain region for which the absolute metabolic changes-induced by lorazepam in cocaine abusers were equivalent to those in controls was the orbitofrontal cortex. These results document an accentuated sensitivity to benzodiazepines in cocaine abusers which is compatible with disrupted GABAergic function in these patients.

  12. Alcohol Test

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The recent alcohol tax increase poses a challenge to China’s white spirits makers Alcohol, rather than wine, is an in-dispensable component to Chinese table culture. The financial crisis has failed to affect white spirits sales, but an alcohol tax increase might.

  13. Alcohol Poisoning

    Science.gov (United States)

    ... t be awakened is at risk of dying. Alcohol poisoning is an emergency If you suspect that someone has alcohol poisoning — even if you don't see the ... immediately. Never assume the person will sleep off alcohol poisoning. Be prepared to provide information. If you ...

  14. Incubation of Cue-Induced Craving in Adults Addicted to Cocaine Measured by Electroencephalography.

    Science.gov (United States)

    Parvaz, Muhammad A; Moeller, Scott J; Goldstein, Rita Z

    2016-11-01

    A common trigger for relapse in drug addiction is the experience of craving via exposure to cues previously associated with drug use. Preclinical studies have consistently demonstrated incubation of cue-induced drug-seeking during the initial phase of abstinence, followed by a decline over time. In humans, the incubation effect has been shown for alcohol, nicotine, and methamphetamine addictions, but not for heroin or cocaine addiction. Understanding the trajectory of cue-induced craving during abstinence in humans is of importance for addiction medicine. To assess cue-induced craving for cocaine in humans using both subjective and objective indices of cue-elicited responses. Seventy-six individuals addicted to cocaine with varying durations of abstinence (ie, 2 days, 1 week, 1 month, 6 months, and 1 year) participated in this laboratory-based cross-sectional study from June 19, 2007, to November 26, 2012. The late positive potential component of electroencephalography, a recognized marker of incentive salience, was used to track motivated attention to drug cues across these self-selected groups. Participants also completed subjective ratings of craving for cocaine before presentation of a cue, and ratings of cocaine "liking" (hedonic feelings toward cocaine) and "wanting" (craving for cocaine) after presentation of cocaine-related pictures. Data analysis was conducted from June 5, 2015, to March 30, 2016. The late positive potential amplitudes and ratings of liking and wanting cocaine in response to cocaine-related pictures were quantified and compared across groups. Among the 76 individuals addicted to cocaine, 19 (25%) were abstinent for 2 days, 20 (26%) were abstinent for 1 week, 15 (20%) were abstinent for 1 month, 12 (16%) were abstinent for 6 months, and 10 (13%) were abstinent for 1 year. In response to drug cues, the mean (SD) late positive potential amplitudes showed a parabolic trajectory that was higher at 1 (1.26 [1.36] µV) and 6 (1.17 [1.19] µ

  15. Prenatal education for congenital toxoplasmosis.

    Science.gov (United States)

    Di Mario, Simona; Basevi, Vittorio; Gagliotti, Carlo; Spettoli, Daniela; Gori, Gianfranco; D'Amico, Roberto; Magrini, Nicola

    2015-10-23

    Congenital toxoplasmosis is considered a rare but potentially severe infection. Prenatal education about congenital toxoplasmosis could be the most efficient and least harmful intervention, yet its effectiveness is uncertain. To assess the effects of prenatal education for preventing congenital toxoplasmosis. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015), and reference lists of relevant papers, reviews and websites. Randomized and quasi-randomized controlled trials of all types of prenatal education on toxoplasmosis infection during pregnancy. Cluster-randomized trials were eligible for inclusion. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two cluster-randomized controlled trials (RCTs) (involving a total of 5455 women) met the inclusion criteria. The two included trials measured the effectiveness of the intervention in different ways, which meant that meta-analysis of the results was not possible. The overall quality of the two studies, as assessed using the GRADE approach, was low, with high risk of detection and attrition bias in both included trials.One trial (432 women enrolled) conducted in Canada was judged of low methodological quality. This trial did not report on any of the review's pre-specified primary outcomes and the secondary outcomes reported results only as P values. Moreover, losses to follow-up were high (34%, 147 out of 432 women initially enrolled). The authors concluded that prenatal education can effectively change pregnant women's behavior as it increased pet, personal and food hygiene. The second trial conducted in France was also judged of low methodological quality. Losses to follow-up were also high (44.5%, 2233 out of 5023 women initially enrolled) and differential (40% in the intervention group and 52% in the control group). The authors concluded that prenatal education for congenital toxoplasmoses has a

  16. Treatment of cocaine overdose with lipid emulsion.

    Science.gov (United States)

    Jakkala-Saibaba, R; Morgan, P G; Morton, G L

    2011-12-01

    We describe the management and recovery of a 28-year-old man following a history of overdose by nasal inhalation of cocaine. The patient was presented in a comatose state suffering from seizures and marked cardiovascularly instability. Intravenous lipid emulsion was administered following initial resuscitation and tracheal intubation, as a means of treating persistent cardiac arrhythmias and profound hypotension. Following lipid emulsion therapy, the patient's life-threatening cardiovascular parameters rapidly improved and he recovered well without any side effects, thus being discharged within 2 days. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

  17. A Thermally Stable Form of Bacterial Cocaine Esterase: A Potential Therapeutic Agent for Treatment of Cocaine Abuse

    Energy Technology Data Exchange (ETDEWEB)

    Brim, Remy L.; Nance, Mark R.; Youngstrom, Daniel W.; Narasimhan, Diwahar; Zhan, Chang-Guo; Tesmer, John J.G.; Sunahara, Roger K.; Woods, James H. (Michigan); (Michigan-Med); (Kentucky)

    2010-09-03

    Rhodococcal cocaine esterase (CocE) is an attractive potential treatment for both cocaine overdose and cocaine addiction. CocE directly degrades cocaine into inactive products, whereas traditional small-molecule approaches require blockade of the inhibitory action of cocaine on a diverse array of monoamine transporters and ion channels. The usefulness of wild-type (wt) cocaine esterase is hampered by its inactivation at 37 C. Herein, we characterize the most thermostable form of this enzyme to date, CocE-L169K/G173Q. In vitro kinetic analyses reveal that CocE-L169K/G173Q displays a half-life of 2.9 days at 37 C, which represents a 340-fold improvement over wt and is 15-fold greater than previously reported mutants. Crystallographic analyses of CocE-L169K/G173Q, determined at 1.6-{angstrom} resolution, suggest that stabilization involves enhanced domain-domain interactions involving van der Waals interactions and hydrogen bonding. In vivo rodent studies reveal that intravenous pretreatment with CocE-L169K/G173Q in mice provides protection from cocaine-induced lethality for longer time periods before cocaine administration than wt CocE. Furthermore, intravenous administration (pretreatment) of CocE-L169K/G173Q prevents self-administration of cocaine in a time-dependent manner. Termination of the in vivo effects of CoCE seems to be dependent on, but not proportional to, its clearance from plasma as its half-life is approximately 2.3 h and similar to that of wt CocE (2.2 h). Taken together these data suggest that CocE-L169K/G173Q possesses many of the properties of a biological therapeutic for treating cocaine abuse but requires additional development to improve its serum half-life.