Behavioral consequences of predator stress in the rat elevated T-maze.

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Bulos, Erika Mondin; Pobbe, Roger Luis Henschel; Zangrossi, Helio

2015-07-01

Analyses of the behavioral reactions of rodents to predators have greatly contributed to the understanding of defense-related human psychopathologies such as anxiety and panic.We here investigated the behavioral consequences of exposing male Wistar rats to a live cat using the elevated T-maze test of anxiety. This test allows the measurement of two defensive responses: inhibitory avoidance and escape, which in terms of pathology have been associated with generalized anxiety and panic disorders, respectively. For comparative reasons, the effects of exposure to the cat were also assessed in the elevated plus-maze. The results showed that a 5-min exposure to the cat selectively facilitated inhibitory avoidance acquisition, an anxiogenic effect, without affecting escape expression in the elevated T-maze. This was seen immediately but not 30 min after contact with the predator. This short-lived anxiogenic effect was also detected in the elevated plus-maze. Previous administration of the benzodiazepine anxiolytic diazepam (2 mg/kg) decreased the immediate avoidance response to the predator and the neophobic reaction to a dummy cat used as a control stimulus. The drug also impaired inhibitory avoidance acquisition in the elevated T-maze, indicating an anxiolytic effect, without affecting escape performance. The results indicate that the state of anxiety evoked during contact with the predator generalizes to both elevated plus- and T-mazes, impacting on defensive responses associated with generalized anxiety disorder.

Age-dependent effect of high cholesterol diets on anxiety-like behavior in elevated plus maze test in rats

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2014-01-01

Background Cholesterol is an essential component of brain and nerve cells and is essential for maintaining the function of the nervous system. Epidemiological studies showed that patients suffering from anxiety disorders have higher serum cholesterol levels. In this study, we investigated the influence of high cholesterol diet on anxiety-like behavior in elevated plus maze in animal model and explored the relationship between cholesterol and anxiety-like behavior from the aspect of central neurochemical changes. Methods Young (3 weeks old) and adult (20 weeks old) rats were given a high cholesterol diet for 8 weeks. The anxiety-like behavior in elevated plus maze test and changes of central neurochemical implicated in anxiety were measured. Results In young rats, high cholesterol diet induced anxiolytic-like behavior, decreased serum corticosterone (CORT), increased hippocampal brain-derived neurotrophic factor (BDNF), increased hippocampal mineralocorticoid receptor (MR) and decreased glucocorticoid receptor (GR). In adult rats, high cholesterol diet induced anxiety-like behavior and increase of serum CORT and decrease of hippocampal BDNF comparing with their respective control group that fed the regular diet. Discussion High cholesterol diet induced age-dependent effects on anxiety-like behavior and central neurochemical changes. High cholesterol diet might affect the central nervous system (CNS) function differently, and resulting in different behavior performance of anxiety in different age period. PMID:25179125

Anxiogenic-like effect of acute and chronic fluoxetine on rats tested on the elevated plus-maze

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M.T.A. Silva

1999-03-01

Full Text Available The selective serotonin reuptake inhibitor fluoxetine (FLX is widely prescribed for depression and anxiety-related disorders. On the other hand, enhanced serotonergic transmission is known to be classically related to anxiety. In this study, the effects of acute (5.0 mg/kg and chronic (5.0 mg/kg, 22 days FLX were investigated in both food-deprived and non-deprived rats tested in the elevated plus-maze. Significant main effects of the three factors (drug, food condition and administration regimen were observed, but no interaction between them. The administration of either acute or chronic FLX resulted in an anxiogenic effect, as detected by a significant reduction in the percentage of time spent in the open arms and in the percentage of open arm entries. Food deprivation yielded an anxiolytic-like profile, probably related to changes in locomotor activity. The administration regimen resulted in an anxiolytic profile in chronically treated rats, as would be expected after 22 days of regular handling. The anxiogenic action of acute FLX is consistent with both its neurochemical and clinical profile. The discrepancy between the anxiogenic profile of chronic FLX and its therapeutic uses is discussed in terms of possible differences between the type of anxiety that is measured in the plus-maze and the types of human anxiety that are alleviated by fluoxetine.

Estimation of the level of anxiety in rats: differences in results of open-field test, elevated plus-maze test, and Vogel's conflict test.

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Sudakov, S K; Nazarova, G A; Alekseeva, E V; Bashkatova, V G

2013-07-01

We compared individual anxiety assessed by three standard tests, open-field test, elevated plus-maze test, and Vogel conflict drinking test, in the same animals. No significant correlations between the main anxiety parameters were found in these three experimental models. Groups of animals with high and low anxiety rats were formed by a single parameter and subsequent selection of two extreme groups (10%). It was found that none of the tests could be used for reliable estimation of individual anxiety in rats. The individual anxiety level with high degree of confidence was determined in high-anxiety and low-anxiety rats demonstrating behavioral parameters above and below the mean values in all tests used. Therefore, several tests should be used for evaluation of the individual anxiety or sensitivity to emotional stress.

Influence of spatial and temporal manipulations on the anxiolytic efficacy of chlordiazepoxide in mice previously exposed to the elevated plus-maze.

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Holmes, A; Rodgers, R J

1999-11-01

It has been widely reported that the anxiolytic efficacy of benzodiazepines in the elevated plus-maze test is abolished in subjects (rats or mice) that have been given a single prior undrugged experience of the test apparatus. The present series of experiments was designed to further characterise the key experiential determinants of this intriguing phenomenon in Swiss Webster mice. Using a standard 5 min test duration for both trials, Experiment 1 confirmed the anxiolytic efficacy of chlordiazepoxide (CDP; 5-20 mg/kg) in mice naive to the plus-maze, but a virtual elimination of drug effects in animals that had been pre-exposed to the maze 24 h earlier. Experiments 2 and 3 demonstrated that, while extending the duration of initial exposure to 10 min did not prevent the loss of CDP (10 mg/kg) efficacy in a standard-duration second trial, increasing the duration of both trials reinstated an anxiolytic profile for the compound. Finally, although trial 1 confinement to an open arm did not compromise CDP efficacy when animals were subsequently allowed to freely explore the maze (Experiment 4), closed arm confinement during initial exposure abolished the drug's anxiolytic action upon retest (Experiment 5). In contrast to previous findings in rats, these data suggest that the experientially induced loss of benzodiazepine efficacy in the mouse plus-maze depends rather critically upon prior discovery and exploration of relatively safe areas of the maze (i.e. closed arms). Results are discussed in relation to the hypothesis that the absence of an anxiolytic response to benzodiazepines in plus-maze-experienced subjects reflects the acquisition of an open arm phobia during trial 1.

Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests

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Ribeiro,A.; Ferraz-de-Paula,V.; Pinheiro,M.L.; Palermo-Neto,J.

2009-01-01

The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped...

Multivariate temporal pattern analysis applied to the study of rat behavior in the elevated plus maze: methodological and conceptual highlights.

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Casarrubea, M; Magnusson, M S; Roy, V; Arabo, A; Sorbera, F; Santangelo, A; Faulisi, F; Crescimanno, G

2014-08-30

Aim of this article is to illustrate the application of a multivariate approach known as t-pattern analysis in the study of rat behavior in elevated plus maze. By means of this multivariate approach, significant relationships among behavioral events in the course of time can be described. Both quantitative and t-pattern analyses were utilized to analyze data obtained from fifteen male Wistar rats following a trial 1-trial 2 protocol. In trial 2, in comparison with the initial exposure, mean occurrences of behavioral elements performed in protected zones of the maze showed a significant increase counterbalanced by a significant decrease of mean occurrences of behavioral elements in unprotected zones. Multivariate t-pattern analysis, in trial 1, revealed the presence of 134 t-patterns of different composition. In trial 2, the temporal structure of behavior become more simple, being present only 32 different t-patterns. Behavioral strings and stripes (i.e. graphical representation of each t-pattern onset) of all t-patterns were presented both for trial 1 and trial 2 as well. Finally, percent distributions in the three zones of the maze show a clear-cut increase of t-patterns in closed arm and a significant reduction in the remaining zones. Results show that previous experience deeply modifies the temporal structure of rat behavior in the elevated plus maze. In addition, this article, by highlighting several conceptual, methodological and illustrative aspects on the utilization of t-pattern analysis, could represent a useful background to employ such a refined approach in the study of rat behavior in elevated plus maze. Copyright © 2014 Elsevier B.V. All rights reserved.

Characterization of Peripheral Activity States and Cortical Local Field Potentials of Mice in an Elevated Plus Maze Test.

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Okonogi, Toya; Nakayama, Ryota; Sasaki, Takuya; Ikegaya, Yuji

2018-01-01

Elevated plus maze (EPM) tests have been used to assess animal anxiety levels. Little information is known regarding how physiological activity patterns of the brain-body system are altered during EPM tests. Herein, we monitored cortical local field potentials (LFPs), electrocardiograms (ECGs), electromyograms (EMGs), and respiratory signals in individual mice that were repeatedly exposed to EPM tests. On average, mouse heart rates were higher in open arms. In closed arms, the mice occasionally showed decreased heart and respiratory rates lasting for several seconds or minutes, characterized as low-peripheral activity states of peripheral signals. The low-activity states were observed only when the animals were in closed arms, and the frequencies of the states increased as the testing days proceeded. During the low-activity states, the delta and theta powers of cortical LFPs were significantly increased and decreased, respectively. These results demonstrate that cortical oscillations crucially depend on whether an animal exhibits low-activity states in peripheral organs rather than the EPM arm in which the animal is located. These results suggest that combining behavioral tests with physiological makers enables a more accurate evaluation of rodent mental states.

Characterization of Peripheral Activity States and Cortical Local Field Potentials of Mice in an Elevated Plus Maze Test

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Toya Okonogi

2018-04-01

Full Text Available Elevated plus maze (EPM tests have been used to assess animal anxiety levels. Little information is known regarding how physiological activity patterns of the brain-body system are altered during EPM tests. Herein, we monitored cortical local field potentials (LFPs, electrocardiograms (ECGs, electromyograms (EMGs, and respiratory signals in individual mice that were repeatedly exposed to EPM tests. On average, mouse heart rates were higher in open arms. In closed arms, the mice occasionally showed decreased heart and respiratory rates lasting for several seconds or minutes, characterized as low-peripheral activity states of peripheral signals. The low-activity states were observed only when the animals were in closed arms, and the frequencies of the states increased as the testing days proceeded. During the low-activity states, the delta and theta powers of cortical LFPs were significantly increased and decreased, respectively. These results demonstrate that cortical oscillations crucially depend on whether an animal exhibits low-activity states in peripheral organs rather than the EPM arm in which the animal is located. These results suggest that combining behavioral tests with physiological makers enables a more accurate evaluation of rodent mental states.

Dorsal periaqueductal gray stimulation facilitates anxiety-, but not panic-related, defensive responses in rats tested in the elevated T-maze

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Camplesi, M. Jr.; Bortoli, V.C. de; Paula Soares, V. de; Nogueira, R.L.; Zangrossi, H. Jr.

2012-01-01

The escape response to electrical or chemical stimulation of the dorsal periaqueductal gray matter (DPAG) has been associated with panic attacks. In order to explore the validity of the DPAG stimulation model for the study of panic disorder, we determined if the aversive consequences of the electrical or chemical stimulation of this midbrain area can be detected subsequently in the elevated T-maze. This animal model, derived from the elevated plus-maze, permits the measurement in the same rat of a generalized anxiety- and a panic-related defensive response, i.e., inhibitory avoidance and escape, respectively. Facilitation of inhibitory avoidance, suggesting an anxiogenic effect, was detected in male Wistar rats (200-220 g) tested in the elevated T-maze 30 min after DPAG electrical stimulation (current generated by a sine-wave stimulator, frequency at 60 Hz) or after local microinjection of the GABA A receptor antagonist bicuculline (5 pmol). Previous electrical (5, 15, 30 min, or 24 h before testing) or chemical stimulation of this midbrain area did not affect escape performance in the elevated T-maze or locomotion in an open-field. No change in the two behavioral tasks measured by the elevated T-maze was observed after repetitive (3 trials) electrical stimulation of the DPAG. The results indicate that activation of the DPAG caused a short-lived, but selective, increase in defensive behaviors associated with generalized anxiety

Dorsal periaqueductal gray stimulation facilitates anxiety-, but not panic-related, defensive responses in rats tested in the elevated T-maze

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Camplesi, M. Jr. [Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, GO (Brazil); Bortoli, V.C. de [Departamento de Ciências da Saúde, Centro Universitário Norte do Espírito Santo, Universidade Federal do Espírito Santo, São Mateus, ES (Brazil); Paula Soares, V. de [Departamento de Biofísica e Farmacologia, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, RN (Brazil); Nogueira, R.L. [Laboratório de Psicologia Comparada, Universidade Estácio de Sá, Rio de Janeiro, RJ (Brazil); Zangrossi, H. Jr. [Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

2012-08-03

The escape response to electrical or chemical stimulation of the dorsal periaqueductal gray matter (DPAG) has been associated with panic attacks. In order to explore the validity of the DPAG stimulation model for the study of panic disorder, we determined if the aversive consequences of the electrical or chemical stimulation of this midbrain area can be detected subsequently in the elevated T-maze. This animal model, derived from the elevated plus-maze, permits the measurement in the same rat of a generalized anxiety- and a panic-related defensive response, i.e., inhibitory avoidance and escape, respectively. Facilitation of inhibitory avoidance, suggesting an anxiogenic effect, was detected in male Wistar rats (200-220 g) tested in the elevated T-maze 30 min after DPAG electrical stimulation (current generated by a sine-wave stimulator, frequency at 60 Hz) or after local microinjection of the GABA{sub A} receptor antagonist bicuculline (5 pmol). Previous electrical (5, 15, 30 min, or 24 h before testing) or chemical stimulation of this midbrain area did not affect escape performance in the elevated T-maze or locomotion in an open-field. No change in the two behavioral tasks measured by the elevated T-maze was observed after repetitive (3 trials) electrical stimulation of the DPAG. The results indicate that activation of the DPAG caused a short-lived, but selective, increase in defensive behaviors associated with generalized anxiety.

Effects of the aqueous extract of Pimpinella anisum L. seeds on exploratory activity and emotional behavior in rats using the open field and elevated plus maze tests.

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Gamberini, Maria Thereza; Rodrigues, Domingos Sávio; Rodrigues, Daniela; Pontes, Victoria Bottino

2015-06-20

Pimpinella anisum L. is considered one of the first plants used for medicinal purposes. Pharmacological actions of the plant on the central nervous system have been proven but previous analyses have focused on anticonvulsant and neuroprotective actions. In traditional medicine worldwide, the use of Pimpinella is commonly recommended as a tranquilizer, although no scientific information supporting this use is available. Therefore, it was decided to investigate the central actions of the plant to observe behavioral responses, with an emphasis on the emotional component. To investigate the effects of the aqueous extract of Pimpinella seeds on exploratory activity and emotional behavior in rats using the open field and elevated plus maze tests. Seeds of Pimpinella were extracted with distilled water, concentrated and freeze-dried yielding the aqueous extract(AE). Rats were divided into four groups: control(water 5 mL/kg, p.o.) and AE 0.5, 1.0 and 2.0 g/kg, p.o. Individual observations were performed in an open field and the parameters locomotor activity, rearing, grooming and defecation were recorded. In elevated plus maze test, rats were divided into four groups: control(water 5 mL/kg, p.o.) and AE 0.5, 1.0 and 2.0 g/kg, p.o. The parameters arm entries, total time spent in open and closed arms; and total number of arrivals at the end of an open or closed arm were recorded for each rat. Among the parameters assessed with the open field test, only rearing was reduced in the AE 0.5 g/kg group. When AE 1.0 g/kg was administered, only the initiation of exploratory activity was delayed, without impairing the animals' general activity. The highest dose of AE (2.0 g/kg) induced a reduction in the animals' habituation during the open field test within the same session, as evidenced by the maintenance of high levels of peripheral locomotion and rearing throughout the test. On the elevated plus maze test, no alterations were observed in the responses of the animals relative to

An elevated plus-maze in mixed reality for studying human anxiety-related behavior.

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Biedermann, Sarah V; Biedermann, Daniel G; Wenzlaff, Frederike; Kurjak, Tim; Nouri, Sawis; Auer, Matthias K; Wiedemann, Klaus; Briken, Peer; Haaker, Jan; Lonsdorf, Tina B; Fuss, Johannes

2017-12-21

A dearth of laboratory tests to study actual human approach-avoidance behavior has complicated translational research on anxiety. The elevated plus-maze (EPM) is the gold standard to assess approach-avoidance behavior in rodents. Here, we translated the EPM to humans using mixed reality through a combination of virtual and real-world elements. In two validation studies, we observed participants' anxiety on a behavioral, physiological, and subjective level. Participants reported higher anxiety on open arms, avoided open arms, and showed an activation of endogenous stress systems. Participants' with high anxiety exhibited higher avoidance. Moreover, open arm avoidance was moderately predicted by participants' acrophobia and sensation seeking, with opposing influences. In a randomized, double blind, placebo controlled experiment, GABAergic stimulation decreased avoidance of open arms while alpha-2-adrenergic antagonism increased avoidance. These findings demonstrate cross-species validity of open arm avoidance as a translational measure of anxiety. We thus introduce the first ecologically valid assay to track actual human approach-avoidance behavior under laboratory conditions.

Effects of single and combined gabapentin use in elevated plus maze and forced swimming tests.

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Kilic, Fatma Sultan; Ismailoglu, Sule; Kaygisiz, Bilgin; Oner, Setenay

2014-10-01

Gabapentin, a third-generation antiepileptic drug, is a structural analogue of γ-aminobutyric acid, which is an important mediator of central nervous system. There is clinical data indicating its effectiveness in the treatment of psychiatric illnesses such as bipolar disorder and anxiety disorders. We aimed to investigate the antidepressant and anxiolytic-like effects and mechanisms of gabapentin in rats. Female Spraque-Dawley rats weighing 250±20 g were used. A total of 13 groups were formed, each containing 8 rats: gabapentin (5, 10, 20, 40 mg/kg), amitriptyline (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg), ketamine (10 mg/kg), gabapentin 20 mg/kg was also combined with amitriptyline (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg) and ketamine (10 mg/kg). All the drugs were used intraperitoneally as single dose. Saline was administered to the control group. Elevated plus maze and forced swimming tests were used as experimental models of anxiety and depression, respectively. It was observed that gabapentin showed an anxiolytic-like and antidepressant-like effect in all doses in rats. Its antidepressant effect was found to be the same as the antidepressant effects of amitriptyline and sertraline. There was no change in the antidepressant effect when gabapentin was combined with amitriptyline and ketamine, but there was an increase when combined with sertraline and diazepam. Gabapentin and amitriptyline showed similar anxiolytic effect, whereas ketamine and diazepam had more potent anxiolytic effect compared with them. These data suggest that gabapentin may possess antidepressant- and anxiolytic-like effects.

Elevated mazes as animal models of anxiety: effects of serotonergic agents

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Simone H. Pinheiro

2007-03-01

Full Text Available This article reviews reported results about the effects of drugs that act upon the serotonergic neurotransmission measured in three elevated mazes that are animal models of anxiety. A bibliographic search has been performed in MEDLINE using different combinations of the key words X-maze, plus-maze, T-maze, serotonin and 5-HT, present in the title and/or the abstract, with no time limit. From the obtained abstracts, several publications were excluded on the basis of the following criteria: review articles that did not report original results, species other than the rat, intracerebral drug administration alone, genetically manipulated rats, and animals having any kind of experimental pathology. The reported results indicate that the effect of drugs on the inhibitory avoidance task performed in the elevated T-maze and on the spatio temporal indexes of anxiety measured in the X and plus mazes correlate with their effect in patients diagnosed with generalized anxiety disorder. In contrast, the drug effects on the one-way escape task in the elevated T-maze predict the drug response of panic disorder patients. Overall, the drug effects assessed with the avoidance task in the T-maze are more consistent than those measured through the anxiety indexes of the X and plus mazes. Therefore, the elevated T-maze is a promising animal model of generalized anxiety and panic disorder.No presente artigo, revisamos resultados publicados relatando efeitos de drogas que atuam na neurotransmissão serotonérgica medidos em três labirintos elevados, que são modelos animais de ansiedade. Realizamos uma busca bibliográfica no MEDLINE, usando diferentes combinações das palavras-chave: X-maze, plus-maze, T-maze, serotonin e 5-HT, presentes no título ou no resumo, sem limite de tempo. Dos resumos obtidos, vários foram excluídos com base nos seguintes critérios: artigos de revisão que não continham resultados originais, espécies diferentes do rato, apenas inje

Critical neuropsychobiological analysis of panic attack- and anticipatory anxiety-like behaviors in rodents confronted with snakes in polygonal arenas and complex labyrinths: a comparison to the elevated plus- and T-maze behavioral tests

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Norberto C. Coimbra

Full Text Available Objective: To compare prey and snake paradigms performed in complex environments to the elevated plus-maze (EPM and T-maze (ETM tests for the study of panic attack- and anticipatory anxiety-like behaviors in rodents. Methods: PubMed was reviewed in search of articles focusing on the plus maze test, EPM, and ETM, as well as on defensive behaviors displayed by threatened rodents. In addition, the authors’ research with polygonal arenas and complex labyrinth (designed by the first author for confrontation between snakes and small rodents was examined. Results: The EPM and ETM tests evoke anxiety/fear-related defensive responses that are pharmacologically validated, whereas the confrontation between rodents and snakes in polygonal arenas with or without shelters or in the complex labyrinth offers ethological conditions for studying more complex defensive behaviors and the effects of anxiolytic and panicolytic drugs. Prey vs. predator paradigms also allow discrimination between non-oriented and oriented escape behavior. Conclusions: Both EPM and ETM simple labyrinths are excellent apparatuses for the study of anxiety- and instinctive fear-related responses, respectively. The confrontation between rodents and snakes in polygonal arenas, however, offers a more ethological environment for addressing both unconditioned and conditioned fear-induced behaviors and the effects of anxiolytic and panicolytic drugs.

Critical neuropsychobiological analysis of panic attack- and anticipatory anxiety-like behaviors in rodents confronted with snakes in polygonal arenas and complex labyrinths: a comparison to the elevated plus- and T-maze behavioral tests.

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Coimbra, Norberto C; Paschoalin-Maurin, Tatiana; Bassi, Gabriel S; Kanashiro, Alexandre; Biagioni, Audrey F; Felippotti, Tatiana T; Elias-Filho, Daoud H; Mendes-Gomes, Joyce; Cysne-Coimbra, Jade P; Almada, Rafael C; Lobão-Soares, Bruno

2017-01-01

To compare prey and snake paradigms performed in complex environments to the elevated plus-maze (EPM) and T-maze (ETM) tests for the study of panic attack- and anticipatory anxiety-like behaviors in rodents. PubMed was reviewed in search of articles focusing on the plus maze test, EPM, and ETM, as well as on defensive behaviors displayed by threatened rodents. In addition, the authors' research with polygonal arenas and complex labyrinth (designed by the first author for confrontation between snakes and small rodents) was examined. The EPM and ETM tests evoke anxiety/fear-related defensive responses that are pharmacologically validated, whereas the confrontation between rodents and snakes in polygonal arenas with or without shelters or in the complex labyrinth offers ethological conditions for studying more complex defensive behaviors and the effects of anxiolytic and panicolytic drugs. Prey vs. predator paradigms also allow discrimination between non-oriented and oriented escape behavior. Both EPM and ETM simple labyrinths are excellent apparatuses for the study of anxiety- and instinctive fear-related responses, respectively. The confrontation between rodents and snakes in polygonal arenas, however, offers a more ethological environment for addressing both unconditioned and conditioned fear-induced behaviors and the effects of anxiolytic and panicolytic drugs.

A novel elevated plus-maze procedure to avoid the one-trial tolerance problem

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Peggy eSchneider

2011-07-01

Full Text Available The elevated plus-maze (EPM test is one of the most commonly used behavioural assays to evaluate anxiety-related behaviour in rodents. It is a rather economic test which usually uses a short (5 min protocol and does not require conditioning of the animals. The critical measure for anxiety is the time spent in the open arms of the maze. A confounding problem of the EPM is the so called one-trial tolerance (OTT, characterised by a marked decrease of open arm exploration in spite of treatment with anxiolytic acting benzodiazepines upon re-exposure to the EPM. This consistent finding is often raised as an evidence for the inappropriateness to re-test rodents in the EPM. However, a reliable re-test paradigm would broaden the usability and effectiveness of this test.Therefore, we tested how a prolongation of the inter-trial interval to 28 days (instead of the usual 24 hours, and an additional change of the testing room would affect the open arm time and other behaviours on the EPM. In two experiments, drug naive Wistar rats were exposed to the EPM on trial 1, and treated intraperitoneally with either vehicle or midazolam (0.25 mg/kg 30 min before trial 2. Then, trial 2 (28 days after trial 1 was carried out in either the same testing room (Exp. 1 or a second unfamiliar room (Exp. 2.Twenty-eight days after trial 1 the open arm time of the rats in the vehicle treated control rats of both experimental groups was comparable to that of the first trial, independent of the testing room. Most importantly, we found that the treatment with the benzodiazepine midazolam had a significantly anxiolytic-like (i.e. increase of open arm time effect in trial 2 only when conducted in the previously unfamiliar testing room (Exp. 2. We suggest that in order to reliably re-test the EPM and to prevent confounding effects due to the OTT, an inter-trial interval of 28 days and a change in testing rooms reinstates anxiolytic-like actions of benzodiazepines

The Effects of Histaminergic Agents in the Nucleus ccumbens of Rats in the Elevated Plus-Maze Test of Anxiety

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Ameneh Rezayof

2010-05-01

Full Text Available "n Objective: "n The nucleus accumbens (NAc receive histaminergic neurons from tuberomammillary nuclei. There are reports indicating that central histamine systems are involved in many physiological behavioral processes, including anxiety. The aim of the present study was to assess whether the histaminergic system of the NAc is involved in anxiety-related behaviors. Methods: Rats were anesthetized with intra-peritoneal injection of ketamine hydrochloride, plus xylazine and then were placed in a stereotaxic apparatus. In addition, two stainless-steel cannuale were placed 2 mm above the nucleus accumbens shell. Seven days after recovery from surgery, the behavioral testing was started. As a model of anxiety, the elevated plus maze which is a useful test to investigate the effects of anxiogenic or anxiolytic drugs in rodents, was used in male Wistar rats.  "nResults: Intra-NAc administration of histamine (0.01, 0.1 and 1 µg/rat increased the percentage of open arm time (%OAT and open arm entries (%OAE ,but not locomotor activity, indicating an anxiolytic response. Furthermore, bilateral  microinjections of different doses of the H1 receptor  antagonist pyrilamine (0.001, 0.01, 0.1 and 1 µg/rat or the H2 receptor antagonist ranitidine (0.001, 0.01, 0.1 and 1 µg/rat into the NAc increased %OAT and %OAE , but not locomotor activity. However, both histamine and histamine receptor antagonists showed an anxiolytic-like effect ; the antagonists (1 µg/rat also decreased the histamine response. "n "n Conclusion: The results may indicate a modulatory effect for the H1 and H2 histamine receptors of nucleus accumbens in the anxiety behavior of rats.

GPR30 activation decreases anxiety in the open field test but not in the elevated plus maze test in female mice.

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Anchan, Divya; Clark, Sara; Pollard, Kevin; Vasudevan, Nandini

2014-01-01

The GPR30 is a novel estrogen receptor (ER) that is a candidate membrane ER based on its binding to 17β estradiol and its rapid signaling properties such as activation of the extracellular-regulated kinase (ERK) pathway. Its distribution in the mouse limbic system predicts a role for this receptor in the estrogenic modulation of anxiety behaviors in the mouse. A previous study showed that chronic administration of a selective agonist to the GPR30 receptor, G-1, in the female rat can improve spatial memory, suggesting that GPR30 plays a role in hippocampal-dependent cognition. In this study, we investigated the effect of a similar chronic administration of G-1 on behaviors that denote anxiety in adult ovariectomized female mice, using the elevated plus maze (EPM) and the open field test as well as the activation of the ERK pathway in the hippocampus. Although estradiol benzoate had no effect on behaviors in the EPM or the open field, G-1 had an anxiolytic effect solely in the open field that was independent of ERK signaling in either the ventral or dorsal hippocampus. Such an anxiolytic effect may underlie the ability of G-1 to increase spatial memory, by acting on the hippocampus.

Effects of periadolescent fluoxetine and paroxetine on elevated plus-maze, acoustic startle, and swimming immobility in rats while on and off-drug.

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Vorhees, Charles V; Morford, LaRonda R; Graham, Devon L; Skelton, Matthew R; Williams, Michael T

2011-10-05

Whether selective serotonin reuptake inhibitors (SSRIs) exposure during adolescent brain development causes lasting effects remains unresolved. Assess the effects of fluoxetine and paroxetine 60 days after adolescent exposure compared with when on-drug. Male Sprague-Dawley littermates (41 litters) were gavaged on postnatal days 33-53 with fluoxetine (3 or 10 mg/kg/day), paroxetine (3, 10 or, 17 mg/kg/day), or water; half were tested while on-drug (21 litters) and half after 60 days off-drug (20 litters). The highest dose of the drugs reduced body weight gain during treatment that rebounded 1 week post-treatment. On-drug, no significant group differences were found on elevated plus maze time-in-open, zone entries, or latency to first open entry; however, the high dose of paroxetine significantly reduced head-dips (N=20/group). No significant effects were found on-drug for acoustic startle response/prepulse inhibition (ASR/PPI) although a trend (pfluoxetine and paroxetine (N=20-21/group). No differences on immobility time were seen in the Porsolt forced swim test or in plasma corticosterone at the end of forced swim (N-19-21/group). Off-drug, no effects were seen in the elevated plus maze (N=16/group), ASR/PPI (N=20/group), forced swim (N=19-20/group), or plasma corticosterone (N=19/group). At the doses tested, fluoxetine and paroxetine induced minor effects with drug on-board but no residual, long-term adverse effects in rats 60 days after drug discontinuation. The data provide no evidence that fluoxetine or paroxetine have long-term adverse effects on the behaviors measured here after adolescent to young adult exposure.

Anxiolytic-like effect of Rauvolfia ligustrina Willd: ex Roem. & Schult., Apocynaceae, in the elevated plus-maze and hole-board tests

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Sueli Mendonça Netto

Full Text Available Rauvolfia ligustrina Willd. ex Roem. & Schult. (Apocynaceae, popularly known as "arrebenta-boi" and "paratudo". In behavioral screening ethanol extract of R. ligustrina roots demonstrated depressant effect on the CNS and anticonvulsant properties. The purpose of this study was to characterize the putative anxiolytic-like effects of the ethanol extract of Rauvolfia ligustrina roots (EER using the elevated plus maze (EPM and the hole-board apparatus in rodents. This extract, administered intraperitoneally, in different doses (3.9, 7.8 and 15.6 mg/kg was able to increase significantly the number of entries (p < 0.05, as well as the time spent in the open arms of the EPM, indicating an anxiolytic-like effect. Additionally, EER-treated (3.9 and 7.8 mg/kg increased significantly the number of border visit and head-dipping. This data suggest an anxiolytic effect of EER in animal models of anxiety.

Relations between open-field, elevated plus-maze, and emergence tests in C57BL/6JIco and BALB/cAnN@Ico mice injected with ethanol.

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Lalonde, R; Strazielle, C

2012-04-01

The effects of ethanol were examined on three tests of exploratory activity in two mouse strains. Although ethanol reduced open-field rearing in both strains, it increased ambulation only in the less active BALB/cAnN@Ico strain, not in the C57BL/6JIco strain. Likewise, ethanol increased open and enclosed arm entries in the elevated plus-maze only in the more anxious BALB/cAnN@Ico strain. However, both strains injected with ethanol emerged faster than placebo from a small chamber at doses not affecting behaviors in the other two tests. Significant correlations were found between emergence latencies on one hand and either slow stereotyped movements or open and enclosed arm entries on the other. The strain-specific effects may be attributable to differences in GABA(A) -related receptor binding or catalase activity. © 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.

Effects of early maternal separation on the performance in the elevated plus maze in adult rats

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Leon Rodriguez, Diego Armando; Duenas Gomez, Zulma Janeth

2012-01-01

It has been demonstrated that disruption of mother pup interaction during early life exerts long lasting effects on the brain and behavioral development. Therefore subjects exposed to early maternal separation stress (MS) show variations in anxiety like behaviors. The aim of this study was to investigate the specific effects of SMT stress on anxiety like behaviors in adult male and female wistar rats. Rats were housed with reversed light dark cycle (light on at 7 p.m., off at 7 a.m.), water and food ad libitum. Separation was carried out in postnatal days 1 to 21, twice daily in dark cycle (7:00 a 10:00 y 13:00 a 16:00 p.m.). The anxiety like behaviors were tested through the elevated plus maze (EPM) when the pups reached 230 g of weigh. We found that the MS stress has sex specific effects on anxiety like behaviors: the maternal separated females displayed a lesser anxious outline than the not separated ones and the separated males showed a large exploration/avoidance conflict. These results confirm previous effects of our labs, which may be related to an interaction between vulnerability to environmental challenge and maternal care compensatory behaviors

Interaction between morphine and noradrenergic system of basolateral amygdala on anxiety and memory in the elevated plus-maze test based on a test-retest paradigm.

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Valizadegan, Farhad; Oryan, Shahrbanoo; Nasehi, Mohammad; Zarrindast, Mohammad Reza

2013-05-01

The amygdala is the key brain structure for anxiety and emotional memory storage. We examined the involvement of β-adrenoreceptors in the basolateral amygdala (BLA) and their interaction with morphine in modulating these behaviors. The elevated plus-maze has been employed for investigating anxiety and memory. Male Wistar rats were used for this test. We injected morphine (4, 5, and 6 mg/kg) intraperitoneally, while salbutamol (albuterol) (1, 2, and 4 μg/rat) and propranolol (1, 2, and 4 μg/rat) were injected into the BLA. Open- arms time percentage (%OAT), open- arms entry percentage (%OAE), and locomotor activity were determined by this behavioral test. Retention was tested 24 hours later. Intraperitoneal injection of morphine (6 mg/kg) had an anxiolytic-like effect and improvement of memory. The highest dose of salbutamol decreased the anxiety parameters in test session and improved the memory in retest session. Coadministration of salbutamol and ineffective dose of morphine presenting anxiolytic response. In this case, the memory was improved. Intra-BLA administration of propranolol (4 μg/rat) decreased %OAT in the test session, while had no effect on memory formation. Coadministration of propranolol and morphine (6 mg/kg) showed an increase in %OAT. There was not any significant change in the above- mentioned parameter in the retest session. Coadministration of morphine and propranolol with the effective dose of salbutamol showed that propranolol could reverse anxiolytic-like effect. We found that opioidergic and β-adrenergic systems have the same effects on anxiety and memory in the BLA; but these effects are independent of each other.

Influence of lactation on motor activity and elevated plus maze behavior

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Silva M.R.P.

1997-01-01

Full Text Available Lactating rats show less noise-induced freezing and fewer inhibitory responses on the 6th day post-delivery when submitted to water and food deprivation in a classical conflict paradigm. Lactating mice go more often to the illuminated chamber in a light-dark cage and stay longer in it than virgin females. The present study was designed to assess the influence of this physiological state, i.e. lactation, on the elevated plus maze (EPM and open-field behavior in adult female rats. Total (TL and central (CL locomotion and rearing (RF frequencies were measured in an open-field. Number of entries into the open and closed arms as well as the time spent in each of these arms were measured in the EPM. Percent time spent and number of entries into the open arms were calculated and compared. In the open-field, TL was significantly decreased (115 ± 10.6 vs 150 ± 11.6 while CL and RF did not differ from those presented by virgin rats. In the EPM, lactating rats displayed a significant reduction in percent time spent (10.9 ± 1.5 vs 17.4 ± 2.3 in the open arms as well as a tendency to a reduction in percent entries into the open arms (35.7 ± 4.7 vs 45.7 ± 4.3. These results show that the physiological state of lactation modulates the open-field and EPM behaviors in rats

Role of thirst and visual barriers in the differential behavior displayed by streptozotocin-treated rats in the elevated plus-maze and the open field test.

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Rebolledo-Solleiro, Daniela; Crespo-Ramírez, Minerva; Roldán-Roldán, Gabriel; Hiriart, Marcia; Pérez de la Mora, Miguel

2013-08-15

Conflicting results have been obtained by several groups when studying the effects of streptozotocin (STZ)-treated rats in the elevated plus-maze (EPM). Since thirst is a prominent feature in STZ-induced diabetic-like condition, we studied whether the walls of the closed arms of the EPM, by limiting the search for water in the environment, may contribute to the observed differential behavioral outcomes. The aim of this study was to ascertain whether visual barriers within the EPM have an influence on the behavior of STZ-treated rats in this test of anxiety. A striking similarity between STZ-treated (50 mg/kg, i.p., in two consecutive days) and water deprived rats (72 h) was found in exploratory behavior in the EPM, showing an anxiolytic-like profile. However the anxiolytic response of STZ-treated rats exposed to the EPM shifts into an anxiogenic profile when they are subsequently tested in the open-field test, which unlike the EPM is devoid of visual barriers. Likewise, water deprived rats (72 h) also showed an anxiogenic profile when they were exposed to the open-field test. Our results indicate that experimental outcomes based on EPM observations can be misleading when studying physiological or pathological conditions, e.g. diabetes, in which thirst may increase exploratory behavior. © 2013.

Dansyl-PQRamide, a putative antagonist of NPFF receptors, reduces anxiety-like behavior of ethanol withdrawal in a plus-maze test in rats.

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Kotlinska, Jolanta; Pachuta, Agnieszka; Bochenski, Marcin; Silberring, Jerzy

2009-06-01

Much evidence indicates that endogenous opioid peptides are involved in effects caused by ethanol. The aim of the present study was to determine whether dansyl-PQR amide, a putative antagonist of receptors for an anti-opioid peptide-neuropeptide FF (NPFF) could affect anxiety-like behavior measured during withdrawal from acute-, and chronic ethanol administration in the elevated plus maze test in rats. Our study indicated that intracerebroventricular (i.c.v.) administration of dansyl-PQRamide (2.4 and 4.8 nmol) reversed anxiety-like behavior measured as a percent time spent in the open arms, and a percent open arm entries onto the open arms in the elevated plus-maze test in rats. These effects were inhibited by NPFF (10 and/or 20 nmol, i.c.v.) in the experiments performed during withdrawal from acute- and chronic ethanol administration. During withdrawal from acute ethanol, naloxone (1mg/kg, i.p.), a nonselective opioid receptor antagonist, attenuated only an increased percent time spent in the open arms induced by dansyl-PQR amide (4.8 nmol). Dansyl-PQR amide, NPFF and naloxone given alone to naive rats did not have influence on spontaneous locomotor activity of animals. Furthermore, NPFF potentiated anxiety-like behavior during withdrawal from chronic, but not acute, ethanol administration in rats. Our data suggest that NPFF system is involved in regulation of affective symptoms of ethanol withdrawal. It seems that involvement of the NPFF system in ethanol withdrawal anxiety-like behavior is associated with regulation of the opioid system activity.

Effects of interleukin-1beta and lipopolysaccharide on behavior of mice in the elevated plus-maze and open field tests.

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Swiergiel, Artur H; Dunn, Adrian J

2007-04-01

It has been postulated that infections, inflammatory processes and resulting cytokines may be causative factors in emotional disorders, including depression and anxiety. Support for this possibility has been sought in studies of animal behavior following administration of interleukin-1 (IL-1) and lipopolysaccharide (LPS). However, such treatments induce a variety of behavioral responses, collectively known as sickness behavior, some of which could affect the performance in tests used to assess anxiety and depression. Thus the effects of peripheral administration of IL-1beta and LPS on the behavior of mice were studied in the elevated plus-maze (EPM) and the open field (OF). Mouse IL-1beta (30, 100, 300, and 1000 ng) was injected intraperitoneally 30 or 60 min, and LPS (0.5, 1 and 5 microg) 120 min before the tests. IL-1beta and LPS induced dose-dependent decreases in open arm entries and the time spent on the open arms in the EPM, effects considered to reflect anxiety-like behavior. However, entries to all arms were also reduced in a dose-dependent manner, indicating a decrease in general activity. In the OF, IL-1beta and LPS decreased the number of line crossings in the center of the field, that can also be considered to reflect anxiety-like behavior. However, this effect was accompanied by a similar decrease in line crossings in the periphery, as well as in rears and climbs. Thus the doses of IL-1beta and LPS necessary to induce these effects also decreased locomotor activity in the EPM and OF. Therefore, the behavioral responses induced by IL-1beta and LPS in the EPM and the OF considered to reflect anxiety must be interpreted in the light of this reduction in overall activity. Thus the results do not provide unequivocal support for the suggestion that LPS or IL-1 mediate anxiety. Nevertheless, because infections, endotoxins, and the ensuing cytokines cause alterations in CNS norepinephrine and serotonin, they may contribute to emotionality, and perhaps to

Sex and estrous cycle-dependent changes in neurosteroid and benzodiazepine effects on food consumption and plus-maze learning behaviors in rats.

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Reddy, D S; Kulkarni, S K

1999-01-01

Experiments were designed to investigate the influence of estrous cycle and gender of the rat on the effects of a gamma-aminobutyric acid type A (GABA(A)) receptor active neurosteroid, 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone), the benzodiazepine, triazolam, and a GABA(A) receptor antagonistic neurosteroid, delta5-androsten-3beta-ol-17-one sulfate (dehydroepiandrosterone sulfate), on food intake and elevated plus-maze learning behaviors. Allopregnanolone (0.25 mg/kg, s.c.) and triazolam (0.25 mg/kg, i.p.) produced a hyperphagic effect, while dehydroepiandrosterone sulfate (5 mg/kg, s.c.) elicited an anorectic effect. However, allopregnanolone was more potent in diestrous females, whereas triazolam exhibited significantly higher hyperphagic potency in estrus females. The extent of anorexia following dehydroepiandrosterone sulfate was alike in male and female rats. The triazolam- and allopregnanolone-induced hyperphagic effect was blocked by bicuculline (1 mg/kg, i.p.), a selective GABA(A) receptor antagonist. In contrast to triazolam, the hyperphagic effect of allopregnanolone was insensitive to flumazenil (5 mg/kg, i.p.), a benzodiazepine antagonist. Vehicle-treated diestrous rats displayed moderately higher latencies in the elevated plus-maze learning task than estrus or proestrus females. Although allopregnanolone and triazolam elicited equipotent learning deficits in plus-maze learning in male and female rats, the magnitude of impairment-induced by triazolam was significantly higher in diestrous females than proestrus females. Dehydroepiandrosterone sulfate enhanced memory performance only in male rats. Although the use of the elevated plus-maze as a learning paradigm with benzodiazepines and neurosteroids may be sensitive to changes in anxiety, the differential data suggest that neurosteroid-induced effects are at least partly specific to learning behavior. These results confirm the role of estrous cycle and sex of rats in modifying the potency of

Rats with differential self-grooming expression in the elevated plus-maze do not differ in anxiety-related behaviors.

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Reimer, Adriano Edgar; de Oliveira, Amanda Ribeiro; Diniz, Juliana Belo; Hoexter, Marcelo Queiroz; Chiavegatto, Silvana; Brandão, Marcus Lira

2015-10-01

Individual differences are important biological predictors for reactivity to stressful stimulation. The extent to which trait differences underlie animal's reactions to conditioned and unconditioned fear stimuli, for example, is still to be clarified. Although grooming behavior has been associated with some aspects of the obsessive-compulsive disorder in humans, its relation with other anxiety disorders is still unknown. Given that grooming behavior could be a component of the whole spectrum of these disorders, in the present study we allocated male Wistar rats in low, intermediate and high self-grooming groups according to the duration of such behavior in the elevated plus-maze (EPM). These groups were then evaluated in unconditioned fear tests, such as the EPM and the open-field, and in conditioned fear tests, such as fear-potentiated startle and fear extinction retention. Additionally, we studied the expression of unconditioned behaviors in marble burying test and the sensorimotor gate function with prepulse inhibition test. Neurochemicals and neuroendocrine parameters were also evaluated, with the quantification of basal corticosterone in the plasma, and dopamine, serotonin and their metabolites in brain structures involved with fear processing. In general, rats classified according to grooming expression showed similar performance in all behavioral tests. Accordingly, corticosterone and monoamine concentrations were similar among groups. Thus, despite grooming expression elicited by different approaches--especially pharmacological ones--has been related with some aspects of anxiety disorders, rats with different expression of spontaneous self-grooming in the EPM do not differ in anxiety-like behaviors nor in neurochemical and neuroendocrine parameters generally associated with anxiety disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

Activity in prelimbic cortex is required for adjusting the anxiety response level during the elevated plus-maze retest.

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Stern, C A J; Do Monte, F H M; Gazarini, L; Carobrez, A P; Bertoglio, L J

2010-09-29

The prelimbic (PL) subregion of medial prefrontal cortex has been implicated in anxiety regulation. It is unknown, however, whether PL cortex also serves to fine-tuning the level of anxiety-related behavior exhibited on the next exposure to the same potentially threatening situation. To address this, we infused cobalt (1.0 mM) to temporarily inactivate the PL cortex during testing, post-testing or retesting in the elevated plus-maze (EPM). This protocol was chosen because it allowed us to concurrently investigate anxiety and the process of aversive learning and memory. PL cortex inactivation during the EPM testing increased the exploration of open-arms, substantiating its role in anxiety. PL cortex inactivation during the EPM retesting counteracted the further avoidance to open-arms exhibited by rats. Interestingly, as evidenced by min-by-min analysis, the cobalt-treated group behaved on EPM retesting as did the vehicle-treated group on EPM testing. This result may imply that activity in PL cortex is necessary for retrieving previously learned information that adjusts the anxiety response level on EPM retesting. Alternatively, a simple reduction in anxiety could explain the cobalt-induced increase in retest open-arms exploration. Neither test nor post-test PL cortex inactivation affected the further avoidance to open-arms observed on EPM retesting. To extend the investigation of PL cortex role in the regulation of open-arms avoidance, we infused other drugs prior to testing or retesting in the EPM. Antagonism of PL cortex adrenergic beta-1 receptors with atenolol (10 nmol), cholinergic muscarinic receptors with scopolamine (20 nmol) or glutamatergic N-methyl-d-aspartic acid (NMDA) receptors with AP5 (6.0 nmol) interfered with the level of open-arms exploration on testing, but not on retesting. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of periadolescent fluoxetine and paroxetine on elevated plus-maze, acoustic startle, and swimming immobility in rats while on and off-drug

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Williams Michael T

2011-10-01

Full Text Available Abstract Rationale Whether selective serotonin reuptake inhibitors (SSRIs exposure during adolescent brain development causes lasting effects remains unresolved. Objective Assess the effects of fluoxetine and paroxetine 60 days after adolescent exposure compared with when on-drug. Methods Male Sprague-Dawley littermates (41 litters were gavaged on postnatal days 33-53 with fluoxetine (3 or 10 mg/kg/day, paroxetine (3, 10 or, 17 mg/kg/day, or water; half were tested while on-drug (21 litters and half after 60 days off-drug (20 litters. Results The highest dose of the drugs reduced body weight gain during treatment that rebounded 1 week post-treatment. On-drug, no significant group differences were found on elevated plus maze time-in-open, zone entries, or latency to first open entry; however, the high dose of paroxetine significantly reduced head-dips (N = 20/group. No significant effects were found on-drug for acoustic startle response/prepulse inhibition (ASR/PPI although a trend (p Conclusions The data provide no evidence that fluoxetine or paroxetine have long-term adverse effects on the behaviors measured here after adolescent to young adult exposure.

Anti-anxiety activity of successive extracts of Angelica archangelica Linn. on the elevated T-maze and forced swimming tests in rats.

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Kumar, Dinesh; Bhat, Zulfiqar Ali; Shah, M Y

2012-09-01

Angelica archangelica Linn. is widely used in food and liquor preparations and also in Kashmiri folk medicine to reduce anxiety. We evaluated the anxiolytic effect of successive extracts of A. archangelica linn. (SAE) on rats tested in the elevated T-maze test (an animal model of generalized anxiety) at doses that exhibit antidepressant-like activity in humans. A. archangelica (1 kg) was subjected to successive extraction in a soxhlet apparatus with solvents [petroleum ether (40-60 degrees C), chloroform, ethyl acetate, methanol and decoction with water] in order of increasing polarity (yield: 6.9%, 7.3%, 5.1%, 11.88% and 8.2% w/w, respectively). SAE were evaluated for anxiolytic effects using the elevated T-maze and forced swimming tests in rats. Oral dosing of diazepam (1 mg/kg) and extracts (50, 100 and 200 mg/kg) clearly showed an anxiolytic-like profile in the elevated T-maze test: it increased one-way escape and decreased inhibitory avoidance on the first, third and seventh day. In the forced swimming test, imipramine and SAE showed antidepressant- and anxiolytic-like effects as reflected by increased climbing time, swimming time and decreased immobility time on the first, third and seventh day. Aqueous and methanol extracts showed the most, petroleum ether (40-60 degrees C) and chloroform intermediate, and ethyl acetate the least anxiolytic activity (*P<0.05, **P<0.01, ***P< 0.001) in both models. These results suggest the anti-anxiety activity of various extracts of A. archangelica and strongly justify its use in traditional Indian medicine for the treatment of anxiety.

L-histidine provokes a state-dependent memory retrieval deficit in mice re-exposed to the elevated plus-maze

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K.R. Serafim

2010-01-01

Full Text Available The effects of L-histidine (LH on anxiety and memory retrieval were investigated in adult male Swiss Albino mice (weight 30-35 g using the elevated plus-maze. The test was performed on two consecutive days: trial 1 (T1 and trial 2 (T2. In T1, mice received an intraperitoneal injection of saline (SAL or LH before the test and were then injected again and retested 24 h later. LH had no effect on anxiety at the dose of 200 mg/kg since there was no difference between the SAL-SAL and LH-LH groups at T1 regarding open-arm entries (OAE and open-arm time (OAT (mean ± SEM; OAE: 4.0 ± 0.71, 4.80 ± 1.05; OAT: 40.55 ± 9.90, 51.55 ± 12.10, respectively; P > 0.05, Kruskal-Wallis test, or at the dose of 500 mg/kg (OAE: 5.27 ± 0.73, 4.87 ± 0.66; OAT: 63.93 ± 11.72, 63.58 ± 10.22; P > 0.05, Fisher LSD test. At T2, LH-LH animals did not reduce open-arm activity (OAE and OAT at the dose of 200 mg/kg (T1: 4.87 ± 0.66, T2: 5.47 ± 1.05; T1: 63.58 ± 10.22; T2: 49.01 ± 8.43 for OAE and OAT, respectively; P > 0.05, Wilcoxon test or at the dose of 500 mg/kg (T1: 4.80 ± 1.60, T2: 4.70 ± 1.04; T1: 51.55 ± 12.10, T2: 43.88 ± 10.64 for OAE and OAT, respectively; P > 0.05, Fisher LSD test, showing an inability to evoke memory 24 h later. These data suggest that LH does not act on anxiety but does induce a state-dependent memory retrieval deficit in mice.

Strain-dependent effects of diazepam and the 5-HT2B/2C receptor antagonist SB 206553 in spontaneously hypertensive and Lewis rats tested in the elevated plus-maze

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Takahashi R.N.

2001-01-01

Full Text Available The 5-HT2B/2C receptor antagonist SB 206553 exerts anxiolytic effects in rat models of anxiety. However, these effects have been reported for standard rat strains, thus raising the issue of SB 206553 effects in rat strains displaying different levels of anxiety. Herein, the effects of SB 206553 in a 5-min elevated plus-maze test of anxiety were compared to those of the reference anxiolytic, diazepam, in two rat strains respectively displaying high (Lewis rats and low (spontaneously hypertensive rats, SHR anxiety. Diazepam (0.37, 0.75, or 1.5 mg/kg; 30 min before testing increased in a dose-dependent manner the behavioral measures in SHR, but not in Lewis rats. On the other hand, SB 206553 (1.25, 2.5, or 5 mg/kg; 30 min before testing failed to alter the anxiety parameters in both strains, whereas it increased closed arm entries in Lewis rats, suggesting that it elicited hyperactivity in the latter strain. Accordingly, the hypolocomotor effect of the nonselective 5-HT2B/2C receptor agonist m-chlorophenylpiperazine (1.5 mg/kg ip 20 min before a 15-min exposure to an activity cage was prevented by the 1.25 and 2.5 mg/kg doses of SB 206553 in Lewis rats and SHR, respectively. Compared with SHR, Lewis rats may display a lower response to benzodiazepine-mediated effects and a more efficient control of locomotor activity by 5-HT2B/2C receptors.

Changes in the biogenic amine content of the prefrontal cortex, amygdala, dorsal hippocampus, and nucleus accumbens of rats submitted to single and repeated sessions of the elevated plus-maze test

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Carvalho M.C.

2005-01-01

Full Text Available It has been demonstrated that exposure to a variety of stressful experiences enhances fearful reactions when behavior is tested in current animal models of anxiety. Until now, no study has examined the neurochemical changes during the test and retest sessions of rats submitted to the elevated plus maze (EPM. The present study uses a new approach (HPLC by looking at the changes in dopamine and serotonin levels in the prefrontal cortex, amygdala, dorsal hippocampus, and nucleus accumbens in animals upon single or double exposure to the EPM (one-trial tolerance. The study involved two experiments: i saline or midazolam (0.5 mg/kg before the first trial, and ii saline or midazolam before the second trial. For the biochemical analysis a control group injected with saline and not tested in the EPM was included. Stressful stimuli in the EPM were able to elicit one-trial tolerance to midazolam on re-exposure (61.01%. Significant decreases in serotonin contents occurred in the prefrontal cortex (38.74%, amygdala (78.96%, dorsal hippocampus (70.33%, and nucleus accumbens (73.58% of the animals tested in the EPM (P < 0.05 in all cases in relation to controls not exposed to the EPM. A significant decrease in dopamine content was also observed in the amygdala (54.74%, P < 0.05. These changes were maintained across trials. There was no change in the turnover rates of these monoamines. We suggest that exposure to the EPM causes reduced monoaminergic neurotransmission activity in limbic structures, which appears to underlie the "one-trial tolerance" phenomenon.

Paradoxical increase of exploratory behavior in the elevated plus-maze by rats exposed to two kinds of aversive stimuli

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Morato S.

1997-01-01

Full Text Available Albino rats were submitted to a 24-h period of social isolation (individual housing combined with 0, 1, 2 or 3 twenty-four-hour periods of exposure to different vivaria (novelty and tested in the elevated plus-maze. Results, reported as mean ± SEM for N = 12, show that the time (in seconds spent in the open arms by rats exposed to novelty for 0, 1, 2 and 3 days was 28.3 ± 4.4, 31.6 ± 3.2, 29.1 ± 3.5 and 25.0 ± 3.3, respectively, when grouped in the same vivarium; 29.6 ± 2.7, 7.6 ± 2.1, 9.6 ± 4.4 and 28.5 ± 3.7 when grouped in different vivaria; 2.9 ± 1.1, 1.8 ± 1.0, 2.7 ± 1.1 and 0 ± 0 when isolated in the same vivarium, and 2.6 ± 1.1, 31.5 ± 8.2, 24.8 ± 4.2 and 0 ± 0 when isolated in different vivaria. The number of entries into the open and closed arms followed a similar trend. This indicates that, separately, both exposure to novelty and isolation are aversive manipulations. Paradoxically, when novelty was combined with a concomitant 24-h period of social isolation prior to testing, the decrease in exploratory behavior caused by either of the two aversive manipulations alone was reverted. These results are indicative that less intense anxiety triggers mechanisms mediating less energetic behavior such as freezing, while higher levels trigger mechanisms mediating more vigorous action, such as flight/fight behavior, since the combination of two aversive situations resulted in more exploratory behavior than with either alone. They are also suggestive of habituation to the effects of novelty, since exposure to it for 3 days produced exploratory behavior similar to that of controls

Behavioral effects of diazepam in the murine plus-maze: flumazenil antagonism of enhanced head dipping but not the disinhibition of open-arm avoidance.

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Dalvi, A; Rodgers, R J

1999-04-01

Although it is widely believed that benzodiazepines reduce anxiety through positive allosteric modulation of the GABA(A)-chloride channel complex, this is not the only mechanism through which agents of this class can modify CNS function. Furthermore, a significant number of reports of apparent flumazenil blockade of diazepam anxiolysis in animal models have paid limited attention to possible intrinsic behavioral actions of the antagonist per se. In the present study, ethological methods were employed to assess in detail the effects of diazepam, flumazenil, and their combination on the behavior of male DBA/2 mice in the elevated plus-maze paradigm. In two experiments, diazepam (1.5 mg/kg) alone reduced open-arm avoidance and increased head dipping, whereas flumazenil (10-40 mg/kg) alone was without significant behavioral effect. However, with the sole exception of head dipping, prior administration of flumazenil (10 and 40 mg/kg) failed to block the behavioral effects of diazepam under present test conditions. These findings imply that the anxiolytic effects of diazepam in the mouse plus-maze are not mediated through flumazenil-sensitive benzodiazepine receptors and that alternate mechanisms must be considered.

Anxiogenic drug administration and elevated plus-maze exposure in rats activate populations of relaxin-3 neurons in the nucleus incertus and serotonergic neurons in the dorsal raphe nucleus.

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Lawther, A J; Clissold, M L; Ma, S; Kent, S; Lowry, C A; Gundlach, A L; Hale, M W

2015-09-10

Anxiety is a complex and adaptive emotional state controlled by a distributed and interconnected network of brain regions, and disruption of these networks is thought to give rise to the behavioral symptoms associated with anxiety disorders in humans. The dorsal raphe nucleus (DR), which contains the majority of forebrain-projecting serotonergic neurons, is implicated in the control of anxiety states and anxiety-related behavior via neuromodulatory effects on these networks. Relaxin-3 is the native neuropeptide ligand for the Gi/o-protein-coupled receptor, RXFP3, and is primarily expressed in the nucleus incertus (NI), a tegmental region immediately caudal to the DR. RXFP3 activation has been shown to modulate anxiety-related behavior in rodents, and RXFP3 mRNA is expressed in the DR. In this study, we examined the response of relaxin-3-containing neurons in the NI and serotonergic neurons in the DR following pharmacologically induced anxiety and exposure to an aversive environment. We administered the anxiogenic drug FG-7142 or vehicle to adult male Wistar rats and, 30 min later, exposed them to either the elevated plus-maze or home cage control conditions. Immunohistochemical detection of c-Fos was used to determine activation of serotonergic neurons in the DR and relaxin-3 neurons in the NI, measured 2h following drug injection. Analysis revealed that FG-7142 administration and exposure to the elevated plus-maze are both associated with an increase in c-Fos expression in relaxin-3-containing neurons in the NI and in serotonergic neurons in dorsal and ventrolateral regions of the DR. These data are consistent with the hypothesis that relaxin-3 systems in the NI and serotonin systems in the DR interact to form part of a network involved in the control of anxiety-related behavior. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Rapid learning of magnetic compass direction by C57BL/6 mice in a 4-armed 'plus' water maze.

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Phillips, John B; Youmans, Paul W; Muheim, Rachel; Sloan, Kelly A; Landler, Lukas; Painter, Michael S; Anderson, Christopher R

2013-01-01

Magnetoreception has been demonstrated in all five vertebrate classes. In rodents, nest building experiments have shown the use of magnetic cues by two families of molerats, Siberian hamsters and C57BL/6 mice. However, assays widely used to study rodent spatial cognition (e.g. water maze, radial arm maze) have failed to provide evidence for the use of magnetic cues. Here we show that C57BL/6 mice can learn the magnetic direction of a submerged platform in a 4-armed (plus) water maze. Naïve mice were given two brief training trials. In each trial, a mouse was confined to one arm of the maze with the submerged platform at the outer end in a predetermined alignment relative to magnetic north. Between trials, the training arm and magnetic field were rotated by 180(°) so that the mouse had to swim in the same magnetic direction to reach the submerged platform. The directional preference of each mouse was tested once in one of four magnetic field alignments by releasing it at the center of the maze with access to all four arms. Equal numbers of responses were obtained from mice tested in the four symmetrical magnetic field alignments. Findings show that two training trials are sufficient for mice to learn the magnetic direction of the submerged platform in a plus water maze. The success of these experiments may be explained by: (1) absence of alternative directional cues (2), rotation of magnetic field alignment, and (3) electromagnetic shielding to minimize radio frequency interference that has been shown to interfere with magnetic compass orientation of birds. These findings confirm that mice have a well-developed magnetic compass, and give further impetus to the question of whether epigeic rodents (e.g., mice and rats) have a photoreceptor-based magnetic compass similar to that found in amphibians and migratory birds.

Papel da luminosidade do biotério no comportamento do rato no labirinto em cruz elevado Role of vivarium illumination in rat behavior in the elevated plus-maze

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Raquel Martinez

2005-08-01

Full Text Available Há pouca informação sobre o efeito dos ambientes onde os ratos são mantidos antes de testes. Para investigar o efeito da iluminação do biotério, ratos Wistar machos foram submetidos a um período de 96 h de iluminação contínua, escuridão contínua ou um ciclo claro escuro de 12:12 h e testados no labirinto em cruz elevado em uma sala iluminada (150 lux ou escura (0 lux. Os resultados mostram que nem a iluminação contínua nem a escuridão contínua do biotério afetam o comportamento dos ratos, quando comparados aos sujeitos mantidos no ciclo claro-escuro de 12 h. A condição de luminosidade durante o teste, no entanto, foi importante: independentemente da condição de iluminação do biotério, os animais testados no escuro exploraram mais os braços abertos do labirinto, um resultado já relatado na literatura e interpretado como diminuição da ansiedade nesse aparato.There is little information about the environments where rats are kept before being tested. In order to investigate the role of vivarium illumination, male Wistar rats were submitted to a 96-h period of continuous illumination, continuous dark or a 12:12 h light/dark cycle and tested in the elevated plus-maze in a lit (150 lux or a dark room (0 lux. Results showed that neither vivarium illumination nor darkness for 96 h altered the rats' behavior in comparison to that of rats kept under the 12-h light/dark cycle. Luminosity during the test, however, was important: no matter what the vivarium illumination was, rats tested in the dark room explored more the open arms of the maze, an already reported result which is interpreted as decreased anxiety in this apparatus.

Diazepam-stress interactions in the rat: effects on autoanalgesia and a plus-maze model of anxiety.

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Taukulis, H K; Goggin, C E

1990-03-01

On six occasions spaced at least a week apart, two groups of rats were subjected to a variety of stressful conditions consisting of a restraint/bright light complex, either alone or in combination with a tail pinch, whole-body inversion, or partial immersion in cold water. One of these groups was injected with diazepam (2.0 mg/kg) 30 min prior to the stressors, while the other group experienced the drug in their home cages the following day. A third group also received the diazepam but was not exposed to the stressors. In three test sessions all animals were injected with either diazepam or saline and were then exposed to a novel stressor: a plus-maze used as a screening device for anxiolytic drugs. This was immediately followed by a tail-flick measure of analgesia. The longest tail-flick latencies, indicating stress-induced analgesia ("autoanalgesia"), were observed in the group that had not been exposed to stress prior to testing. The other two groups exhibited substantially shorter latencies but did not differ from one another, thus showing a "stress inoculation" effect that was uninfluenced by diazepam. In the plus-maze, diazepam tends to increase the amount of time rats will spend in the two exposed arms of the maze relative to the two enclosed arms. This effect was significantly attenuated in the group that had previously experienced the variety of stressors after a diazepam injection, suggesting a learned association between drug and stress that resulted in a diminution of the drug's anxiolytic property.

Rapid learning of magnetic compass direction by C57BL/6 mice in a 4-armed 'plus' water maze.

Directory of Open Access Journals (Sweden)

John B Phillips

Full Text Available Magnetoreception has been demonstrated in all five vertebrate classes. In rodents, nest building experiments have shown the use of magnetic cues by two families of molerats, Siberian hamsters and C57BL/6 mice. However, assays widely used to study rodent spatial cognition (e.g. water maze, radial arm maze have failed to provide evidence for the use of magnetic cues. Here we show that C57BL/6 mice can learn the magnetic direction of a submerged platform in a 4-armed (plus water maze. Naïve mice were given two brief training trials. In each trial, a mouse was confined to one arm of the maze with the submerged platform at the outer end in a predetermined alignment relative to magnetic north. Between trials, the training arm and magnetic field were rotated by 180(° so that the mouse had to swim in the same magnetic direction to reach the submerged platform. The directional preference of each mouse was tested once in one of four magnetic field alignments by releasing it at the center of the maze with access to all four arms. Equal numbers of responses were obtained from mice tested in the four symmetrical magnetic field alignments. Findings show that two training trials are sufficient for mice to learn the magnetic direction of the submerged platform in a plus water maze. The success of these experiments may be explained by: (1 absence of alternative directional cues (2, rotation of magnetic field alignment, and (3 electromagnetic shielding to minimize radio frequency interference that has been shown to interfere with magnetic compass orientation of birds. These findings confirm that mice have a well-developed magnetic compass, and give further impetus to the question of whether epigeic rodents (e.g., mice and rats have a photoreceptor-based magnetic compass similar to that found in amphibians and migratory birds.

Cognitive and Neural Determinants of Response Strategy in the Dual-Solution Plus-Maze Task

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De Leonibus, Elvira; Costantini, Vivian J. A.; Massaro, Antonio; Mandolesi, Georgia; Vanni, Valentina; Luvisetto, Siro; Pavone, Flaminia; Oliverio, Alberto; Mele, Andrea

2011-01-01

Response strategy in the dual-solution plus maze is regarded as a form of stimulus-response learning. In this study, by using an outcome devaluation procedure, we show that it can be based on both action-outcome and stimulus-response habit learning, depending on the amount of training that the animals receive. Furthermore, we show that…

Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities.

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Katayama, K; Yamada, K; Ornthanalai, V G; Inoue, T; Ota, M; Murphy, N P; Aruga, J

2010-02-01

Mutations in SLITRK1 are found in patients with Tourette's syndrome and trichotillomania. SLITRK1 encodes a transmembrane protein containing leucine-rich repeats that is produced predominantly in the nervous system. However, the role of this protein is largely unknown, except that it can modulate neurite outgrowth in vitro. To clarify the role of Slitrk1 in vivo, we developed Slitrk1-knockout mice and analyzed their behavioral and neurochemical phenotypes. Slitrk1-deficient mice exhibited elevated anxiety-like behavior in the elevated plus-maze test as well as increased immobility time in forced swimming and tail suspension tests. Neurochemical analysis revealed that Slitrk1-knockout mice had increased levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol. Administration of clonidine, an alpha2-adrenergic agonist that is frequently used to treat patients with Tourette's syndrome, attenuated the anxiety-like behavior of Slitrk1-deficient mice in the elevated plus-maze test. These results lead us to conclude that noradrenergic mechanisms are involved in the behavioral abnormalities of Slitrk1-deficient mice. Elevated anxiety due to Slitrk1 dysfunction may contribute to the pathogenesis of neuropsychiatric diseases such as Tourette's syndrome and trichotillomania.

Sex differences in a human analogue of the Radial Arm Maze: the "17-Box Maze Test".

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Rahman, Qazi; Abrahams, Sharon; Jussab, Fardin

2005-08-01

This study investigated sex differences in spatial memory using a human analogue of the Radial Arm Maze: a revision on the Nine Box Maze originally developed by called the 17-Box Maze Test herein. The task encourages allocentric spatial processing, dissociates object from spatial memory, and incorporates a within-participants design to provide measures of location and object, working and reference memory. Healthy adult males and females (26 per group) were administered the 17-Box Maze Test, as well as mental rotation and a verbal IQ test. Females made significantly fewer errors on this task than males. However, post hoc analysis revealed that the significant sex difference was specific to object, rather than location, memory measures. These were medium to large effect sizes. The findings raise the issue of task- and component-specific sexual dimorphism in cognitive mapping.

Low-dose thioperamide injected into the cerebellar vermis of mice immediately after exposure to the elevated plus-maze impairs their avoidance behavior on re-exposure to the apparatus

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J. Costa Neto

2013-11-01

Full Text Available The present study investigated the effect of thioperamide (THIO, an H3 histaminergic receptor antagonist, microinjected into the cerebellar vermis on emotional memory consolidation in male Swiss albino mice re-exposed to the elevated plus-maze (EPM. We implanted a guide cannula into the cerebellar vermis using stereotactic surgery. On the third day after surgery, we performed behavioral tests for two consecutive days. On the first day (exposure, the mice (n=10/group were exposed to the EPM and received THIO (0.06, 0.3, or 1.5 ng/0.1 µL immediately after the end of the session. Twenty-four hours later, the mice were re-exposed to the EPM under the same experimental conditions, but without drug injection. A reduction in the exploration of the open arms upon re-exposure to the EPM (percentage of number of entries and time spent in open arms compared with the initial exposure was used as an indicator of learning and memory. One-way analysis of variance (ANOVA followed by the Duncan post hoc test was used to analyze the data. Upon re-exposure, exploratory activity in the open arms was reduced in the control group, and with the two highest THIO doses: 0.3 and 1.5 ng/0.1 µL. No reduction was seen with the lowest THIO dose (0.06 ng/0.1 µL, indicating inhibition of the consolidation of emotional memory. None of the doses interfered with the animals' locomotor activity. We conclude that THIO at the lowest dose (0.06 ng/0.1 µL microinjected into the cerebellum impaired emotional memory consolidation in mice.

FG7142, yohimbine, and βCCE produce anxiogenic-like effects in the elevated plus-maze but do not affect brainstem activated hippocampal theta.

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Yeung, Michelle; Lu, Lily; Hughes, Adam M; Treit, Dallas; Dickson, Clayton T

2013-12-01

The neurobiological underpinnings of anxiety are of paramount importance to selective and efficacious pharmaceutical intervention. Hippocampal theta frequency in urethane anaesthetized rats is suppressed by all known (and some previously unknown) anti-anxiety (anxiolytic) drugs. Although these findings support the predictive validity of this assay, its construct validity (i.e., whether theta frequency actually indexes anxiety per se) has not been a subject of systematic investigation. We reasoned that if anxiolytic drugs suppress hippocampal theta frequency, then drugs that increase anxiety (i.e., anxiogenic agents) should increase theta frequency, thus providing evidence of construct validity. We used three proven anxiogenic drugs--two benzodiazepine receptor inverse agonists, N-methyl-β-carboline-3-carboxamide (FG7142) and β-carboline-3-carboxylate ethyl ester (βCCE), and one α2 noradrenergic receptor antagonist, 17α-hydroxy-yohimban-16α-carboxylic acid methyl ester (yohimbine) as pharmacological probes to assess the construct validity of the theta model. Although all three anxiogenic drugs significantly increased behavioural measures of anxiety in the elevated plus-maze, none of the three increased the frequency of hippocampal theta oscillations in the neurophysiological model. As a positive control, we demonstrated that diazepam, a proven anxiolytic drug, decreased the frequency of hippocampal theta, as in all other studies using this model. Given this discrepancy between the significant effects of anxiogenic drugs in the behavioural model and the null effects of these drugs in the neurophysiological model, we conclude that the construct validity of the hippocampal theta model of anxiety is questionable. Copyright © 2013 Elsevier Ltd. All rights reserved.

Blockade of serotonin 5-HT2A receptors potentiates dopamine D2 activation-induced disruption of pup retrieval on an elevated plus maze, but has no effect on D2 blockade-induced one.

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Nie, Lina; Di, Tianqi; Li, Yu; Cheng, Peng; Li, Ming; Gao, Jun

2018-06-23

Appetitive aspect of rat maternal behavior, such as pup retrieval, is motivationally driven and sensitive to dopamine disturbances. Activation or blockade of dopamine D 2 receptors causes a similar disruption of pup retrieval, which may also reflect an increase in maternal anxiety and/or a disruption of executive function. Recent work indicates that serotonin 5-HT 2A receptors also play an important role in rat maternal behavior. Given the well-known modulation of 5-HT 2A on the mesolimbic and mesocortical dopamine functions, the present study examined the extent to which blockade of 5-HT 2A receptors on dopamine D 2 -mediated maternal effects using a pup retrieval on the elevated plus maze (EPM) test. Sprague-Dawley postpartum female rats were acutely injected with quinpirole (a D 2 agonist, 0.10 and 0.25 mg/kg, sc), or haloperidol (a D 2 antagonist, 0.1 or 0.2 mg/kg, sc), in combination of MDL100907 (a 5-HT 2A receptor antagonist, 1.0 mg/kg, sc, 30 min before quinpirole or haloperidol injection) or saline and tested at 30, 90 and 240 min after quinpirole or haloperidol injection on postpartum days 3 and 7. Quinpirole and haloperidol decreased the number of pup retrieved (an index of maternal motivation) and sequential retrieval score (an index of executive function), prolonged the pup retrieval latencies, reduced the percentage of time spent on the open arms (an index of maternal anxiety), and decreased the distance travelled on the maze in a dose-dependent and time-dependent fashion. MDL100907 treatment by itself had no effect on pup retrieval, but it exacerbated the quinpirole-induced disruption of pup retrieval, but had no effect on the haloperidol-induced one. These findings suggest a complex interactive effect between 5-HT 2A and D 2 receptors on one or several maternal processes (maternal motivation, anxiety and executive function), and support the idea that one molecular mechanism by which 5-HT 2A receptors mediate maternal behavior is through

What does the CBM-maze test measure?

NARCIS (Netherlands)

Muijselaar, M.M.L.; Kendeou, P.; de Jong, P.F.; van den Broek, P.W.

2017-01-01

In this study, we identified the code-related (decoding, fluency) and language comprehension (vocabulary, listening comprehension) demands of the CBM-Maze test, a formative assessment, and compared them to those of the Gates–MacGinitie test, a standardized summative assessment. The demands of these

Influence of magnetic field on zebrafish activity and orientation in a plus maze.

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Osipova, Elena A; Pavlova, Vera V; Nepomnyashchikh, Valentin A; Krylov, Viacheslav V

2016-01-01

We describe an impact of the geomagnetic field (GMF) and its modification on zebrafish's orientation and locomotor activity in a plus maze with four arms oriented to the north, east, south and west. Zebrafish's directional preferences were bimodal in GMF: they visited two arms oriented in opposed directions (east-west) most frequently. This bimodal preference remained stable for same individuals across experiments divided by several days. When the horizontal GMF component was turned 90° clockwise, the preference accordingly shifted by 90° to arms oriented to the north and south. Other modifications of GMF (reversal of both vertical and horizontal GMF components; reversal of vertical component only; and reversal of horizontal component only) did not exert any discernible effect on the orientation of zebrafish. The 90° turn of horizontal component also resulted in a significant increase of fish's locomotor activity in comparison with the natural GMF. This increase became even more pronounced when the horizontal component was repeatedly turned by 90° and back with 1min interval between turns. Our results show that GMF and its variations should be taken into account when interpreting zebrafish's directional preferences and locomotor activity in mazes and other experimental devices. Copyright © 2015. Published by Elsevier B.V.

Effect of fenbendazole on three behavioral tests in male C57BL/6N mice.

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Gadad, Bharathi S; Daher, João P L; Hutchinson, Eric K; Brayton, Cory F; Dawson, Ted M; Pletnikov, Mikhail V; Watson, Julie

2010-11-01

Pinworms are highly contagious parasites of laboratory rodents that often are treated with fenbendazole. To our knowledge, the effect of fenbendazole at therapeutic dosages on behavioral tests in mice has not been evaluated. Here we studied 6-wk-old male C57BL/6N mice. We compared the behavior of control mice (fed regular diet) with 3 groups of mice treated with dietary fenbendazole. Treatment groups were 4 wk of fenbendazole, 2 wk of fenbendazole followed by 2 wk of regular diet, and 2 wk of regular diet followed by 2 wk of fenbendazole. At the end of dietary treatment all groups were tested by open field for central, peripheral and vertical activity; elevated plus maze for anxiety; and rotarod for motor ability and then evaluated by clinical pathology and selected histopathology. Treated and control groups showed no differences in open field or elevated plus maze testing, histopathology, or clinical pathology. However mice treated for 4 wk with fenbendazole or 2 wk of fenbendazole followed by 2 wk regular diet stayed on the rotarod for shorter periods than did controls, and mice treated with 2 wk of regular diet followed by 2 wk fenbendazole showed a trend toward shorter rotarod times. In light of this study, we suggest that open field and elevated plus maze testing is unlikely to be affected by 4 wk fenbendazole treatment in male C57BL/6 mice; however, behavioral tests of motor ability such as rotarod tests may be affected during and for at least 2 wk after fenbendazole treatment.

Neuroanatomical pathways underlying the effects of hypothalamo-hypophysial-adrenal hormones on exploratory activity.

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Lalonde, Robert; Strazielle, Catherine

2017-07-26

When injected via the intracerebroventricular route, corticosterone-releasing hormone (CRH) reduced exploration in the elevated plus-maze, the center region of the open-field, and the large chamber in the defensive withdrawal test. The anxiogenic action of CRH in the elevated plus-maze also occurred when infused in the basolateral amygdala, ventral hippocampus, lateral septum, bed nucleus of the stria terminalis, nucleus accumbens, periaqueductal grey, and medial frontal cortex. The anxiogenic action of CRH in the defensive withdrawal test was reproduced when injected in the locus coeruleus, while the amygdala, hippocampus, lateral septum, nucleus accumbens, and lateral globus pallidus contribute to center zone exploration in the open-field. In addition to elevated plus-maze and open-field tests, the amygdala appears as a target region for CRH-mediated anxiety in the elevated T-maze. Thus, the amygdala is the principal brain region identified with these three tests, and further research must identify the neural circuits underlying this form of anxiety.

A computer vision-based automated Figure-8 maze for working memory test in rodents.

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Pedigo, Samuel F; Song, Eun Young; Jung, Min Whan; Kim, Jeansok J

2006-09-30

The benchmark test for prefrontal cortex (PFC)-mediated working memory in rodents is a delayed alternation task utilizing variations of T-maze or Figure-8 maze, which requires the animals to make specific arm entry responses for reward. In this task, however, manual procedures involved in shaping target behavior, imposing delays between trials and delivering rewards can potentially influence the animal's performance on the maze. Here, we report an automated Figure-8 maze which does not necessitate experimenter-subject interaction during shaping, training or testing. This system incorporates a computer vision system for tracking, motorized gates to impose delays, and automated reward delivery. The maze is controlled by custom software that records the animal's location and activates the gates according to the animal's behavior and a control algorithm. The program performs calculations of task accuracy, tracks movement sequence through the maze, and provides other dependent variables (such as running speed, time spent in different maze locations, activity level during delay). Testing in rats indicates that the performance accuracy is inversely proportional to the delay interval, decreases with PFC lesions, and that animals anticipate timing during long delays. Thus, our automated Figure-8 maze is effective at assessing working memory and provides novel behavioral measures in rodents.

Mice with Sort1 deficiency display normal cognition but elevated anxiety-like behavior.

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Ruan, Chun-Sheng; Yang, Chun-Rui; Li, Jia-Yi; Luo, Hai-Yun; Bobrovskaya, Larisa; Zhou, Xin-Fu

2016-07-01

Exposure to stressful life events plays a central role in the development of mood disorders in vulnerable individuals. However, the mechanisms that link mood disorders to stress are poorly understood. Brain-derived neurotrophic factor (BDNF) has long been implicated in positive regulation of depression and anxiety, while its precursor (proBDNF) recently showed an opposing effect on such mental illnesses. P75(NTR) and sortilin are co-receptors of proBDNF, however, the role of these receptors in mood regulation is not established. Here, we aimed to investigate the role of sortilin in regulating mood-related behaviors and its role in the proBDNF-mediated mood abnormality in mice. We found that sortilin was up-regulated in neocortex (by 78.3%) and hippocampus (by 111%) of chronically stressed mice as assessed by western blot analysis. These changes were associated with decreased mobility in the open field test and increased depression-like behavior in the forced swimming test. We also found that sortilin deficiency in mice resulted in hyperlocomotion in the open field test and increased anxiety-like behavior in both the open field and elevated plus maze tests. No depression-like behavior in the forced swimming test and no deficit in spatial cognition in the Morris water maze test were found in the Sort1-deficient mice. Moreover, the intracellular and extracellular levels of mature BDNF and proBDNF were not changed when sortilin was absent in vivo and in vitro. Finally, we found that both WT and Sort1-deficient mice injected with proBDNF in lateral ventricle displayed increased depression-like behavior in the forced swimming test but not anxiety-like behaviors in the open field and elevated plus maze tests. The present study suggests that sortilin functions as a negative regulator of mood performance and can be a therapeutic target for the treatment of mental illness. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Effects of zolpidem on sedation, anxiety, and memory in the plus-maze discriminative avoidance task.

Science.gov (United States)

Zanin, Karina A; Patti, Camilla L; Sanday, Leandro; Fernandes-Santos, Luciano; Oliveira, Larissa C; Poyares, Dalva; Tufik, Sergio; Frussa-Filho, Roberto

2013-04-01

Zolpidem (Zolp), a hypnotic drug prescribed to treat insomnia, may have negative effects on memory, but reports are inconsistent. We examined the effects of acute doses of Zolp (2, 5, or 10 mg/kg, i.p.) on memory formation (learning, consolidation, and retrieval) using the plus-maze discriminative avoidance task. Mice were acutely treated with Zolp 30 min before training or testing. In addition, the effects of Zolp and midazolam (Mid; a classic benzodiazepine) on consolidation at different time points were examined. The possible role of state dependency was investigated using combined pre-training and pre-test treatments. Zolp produced a dose-dependent sedative effect, without modifying anxiety-like behavior. The pre-training administration of 5 or 10 mg/kg resulted in retention deficits. When administered immediately after training or before testing, memory was preserved. Zolp post-training administration (2 or 3 h) impaired subsequent memory. There was no participation of state dependency phenomenon in the amnestic effects of Zolp. Similar to Zolp, Mid impaired memory consolidation when administered 1 h after training. Amnestic effects occurred when Zolp was administered either before or 2-3 h after training. These memory deficits are not related to state dependency. Moreover, Zolp did not impair memory retrieval. Notably, the memory-impairing effects of Zolp are similar to those of Mid, with the exception of the time point at which the drug can modify consolidation. Finally, the memory effects were unrelated to sedation or anxiolysis.

Anxiolytic-like effects after vector-mediated overexpression of neuropeptide Y in the amygdala and hippocampus of mice

DEFF Research Database (Denmark)

Christiansen, Søren Hofman Oliveira; Olesen, Mikkel Vestergaard; Gøtzsche, Casper René

2014-01-01

, injections of rAAV-NPY caused significant anxiolytic-like effect in the open field, elevated plus maze, and light-dark transition tests. In the hippocampus, rAAV-NPY treatment was associated with anxiolytic-like effect only in the elevated plus maze. No additive effect was observed after combined r....... Using a recombinant adeno-associated viral (rAAV) vector, we addressed this idea by testing effects on anxiolytic- and depression-like behaviours in adult mice after overexpression of NPY transgene in the amygdala and/or hippocampus, two brain regions implicated in emotional behaviours. In the amygdala......AAV-NPY injection into both the amygdala and hippocampus where anxiolytic-like effect was found in the elevated plus maze and light-dark transition tests. Antidepressant-like effects were not detected in any of the rAAV-NPY injected groups. Immobility was even increased in the tail suspension and forced swim tests...

Recurrent hypoglycemia increases anxiety and amygdala norepinephrine release during subsequent hypoglycemia

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Ewan eMcNay

2015-11-01

Full Text Available Recurrent hypoglycemia (RH is a common and debilitating side effect of therapy in patients with both type 1 and, increasingly, type 2 diabetes. Previous studies in rats have shown marked effects of RH on subsequent hippocampal behavioral, metabolic, and synaptic processes. In addition to impaired memory, patients experiencing RH report alterations in cognitive processes that include mood and anxiety, suggesting that RH may also affect amygdala function. We tested the impact of RH on amygdala function using an elevated plus-maze test of anxiety together with in vivo amygdala microdialysis for norepinephrine (NEp, a widely used marker of basolateral amygdala cognitive processes. In contrast to findings in the hippocampus and pre-frontal cortex, neither RH nor acute hypoglycemia alone significantly affected plus-maze performance or NEp release. However, animals tested when hypoglycemic who had previously experienced RH had elevated amygdala NEp during plus-maze testing, accompanied by increased anxiety (i.e. less time spent in the open arms of the plus-maze. The results show that RH has widespread effects on subsequent brain function, which vary by neural system.

Effects of rolipram and zaprinast on learning and memory in the Morris water maze and radial arm maze tests in naive mice.

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Akar, F; Mutlu, O; Celikyurt, I K; Ulak, G; Erden, F; Bektas, E; Tanyeri, P

2015-02-01

Inhibition of phosphodiesterase 5 (PDE) improved recognition memory and counteracted spatial learning impairment induced by nitric oxide synthase (NOS) inhibition in recent studies. Aim of this study was to investigate effects of rolipram, a PDE4 inhibitor and zaprinast, a PDE5 inhibitor, on learning and memory in Morris water maze (MWM) and radial arm maze (RAM) tests in naive mice. Male Balb-c mice were treated subchronically with zaprinast (3 and 10 mg/kg) and rolipram (0.05 and 0.1 mg/kg) for 6 days in the MWM test and acutely before the retention trial of radial arm maze test. Rolipram (0.05 and 0.1 mg/kg) significantly decreased escape latency between 2(nd) and 5(th) sessions, while zaprinast (10 mg/kg) significantly decreased escape latency only in 2(nd) session. Rolipram (0.05 and 0.1 mg/kg) and zaprinast (10 mg/kg) significantly increased time spent in escape platform's quadrant in probe trial of MWM test; only rolipram decreased mean distance to platform, while zaprinast had no effect on mean distance to platform. Zaprinast (3 and 10 mg/kg) significantly decreased number of errors compared to control group, while rolipram (0.05 and 0.1mg/kg) had no effect on number of errors in retention trial of RAM test. Rolipram (0.05 and 0.1 mg/kg) and zaprinast (10 mg/kg) significantly decreased time spent to complete retention trial (latency) compared to control group. Our study revealed that both zaprinast and rolipram enhanced spatial memory in MWM, while zaprinast seems to have more memory enhancing effects compared to rolipram in radial arm maze test. © Georg Thieme Verlag KG Stuttgart · New York.

Utility of finger maze test for learning and memory abilities in infants of cynomolgus monkeys exposed to thiamazole.

Science.gov (United States)

Inoue, Ayumi; Arima, Akihiro; Kato, Hirohito; Ebihara, Shizufumi

2014-11-01

A new type of learning and memory test using a finger maze was conducted in infant cynomolgus monkeys that were exposed to thiamazole (2 and 3.5 mg/kg per day to pregnant animals orally) during the fetal period (gestational days 120 to 150). We modified Tsuchida's original finger maze test method by reducing the number of trials per day and simplifying the criteria for achievement of training, and we added a long-term memory test. In the memory test, thiamazole-exposed infants required greater time to complete the finger maze test than the control infants although no effect was noted in the training or learning test. The results suggest that an impaired long-term memory could be detected by our modified finger maze test. © 2014 Japanese Teratology Society.

The effect of D2 agonist versus D2 antagonist on the fear behavior in the male rats using plus-maze method: the prospective study

Directory of Open Access Journals (Sweden)

Sabzehkhah S

2009-11-01

Full Text Available "nBackground: Dopaminergic is the most important neurotransmitter is fear. The dopaminergic mesolimbic pathway has essential role in excitable behavior, and it's role in Parkinson disease. The aim of this research in study, the effect of dopaminergic pathway in fear response. "n"nMethods: The elevated plus maze was used in combination with the percentage of time spent in the open arms of the maze (OAT% and the percentage of entries into the open arms (OAE% to measure fear. Increases in the OAT% and OAE% indicate an anxiolytic effect (reduction in anxiety, whereas decreases in the OAE% and OAT% indicate an anxiogenic effect. After five days, the rats were injected with saline and different doses of sulpiride and Bromocriptine."n"nResults: Results showed that intracerebroventricular administration of sulpiride, in the doses of 5, 20μg/rat and bromocriptine, D2 agonist in doses 65, 95μg/rat produced a significant effect comparing to sham groups (p<0.05. While intracerebroventricular administration of sulpiride 15, 10μg/rat, and bromocriptine 70, 80μg/rat, did not show any significant effect comparing with sham group (p<0.05. In the current research intracerebroventricular administration of sulpiride, D2 antagonist at the doses of 5, 10, 15, 20μg/rat and Bromocriptine, D2 agonist in the doses of 65, 70, 80, 95μg/rat were used and theire effect on the fear behavior were studied. "n"nConclusions: The possible effect of Dopaminergic system in the fear process, especially D2 receptor increase fear.

Effects of an electrolytic lesion of the prelimbic area on anxiety-related and cognitive tasks in the rat

NARCIS (Netherlands)

Gispen, W.H.; Maaswinkel, H.; Spruijt, B.M.

1996-01-01

The aim of this paper was to study the role of the prelimbic area of rats in response selection. A bilateral electrolytic lesion was made in the prelimbic area. The rats were tested in the Morris water-maze, the conditioned shock-prod burying test, the elevated plus-maze, a modified open field test,

The Effects of Inhaled Pimpinella peregrina Essential Oil on Scopolamine-Induced Memory Impairment, Anxiety, and Depression in Laboratory Rats.

Science.gov (United States)

Aydin, Emel; Hritcu, Lucian; Dogan, Gulden; Hayta, Sukru; Bagci, Eyup

2016-11-01

In the present study, we identified the effects of inhaled Pimpinella peregrina essential oil (1 and 3 %, for 21 continuous days) on scopolamine-induced memory impairment, anxiety, and depression in laboratory rats. Y-maze and radial arm-maze tests were used for assessing memory processes. Also, the anxiety and depressive responses were studied by means of the elevated plus-maze and forced swimming tests. The scopolamine alone-treated rats exhibited the following: decrease of the spontaneous alternation percentage in Y-maze test, increase of the number of working and reference memory errors in radial arm-maze test, along with decrease of the exploratory activity, the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming time and increase of immobility time within forced swimming test. Inhalation of the P. peregrina essential oil significantly improved memory formation and exhibited anxiolytic- and antidepressant-like effects in scopolamine-treated rats. Our results suggest that the P. peregrina essential oil inhalation ameliorates scopolamine-induced memory impairment, anxiety, and depression. Moreover, studies on the P. peregrina essential oil may open a new therapeutic window for the prevention of neurological abnormalities closely related to Alzheimer's disease.

Prenatal and lactational exposure to low-doses of bisphenol A alters adult mice behavior.

Science.gov (United States)

Nakamura, Keiko; Itoh, Kyoko; Dai, Hongmei; Han, Longzhe; Wang, Xiaohang; Kato, Shingo; Sugimoto, Tohru; Fushiki, Shinji

2012-01-01

Bisphenol A (BPA) is an endocrine-disrupting chemical, widely used in dentistry and various industries. We previously reported that BPA affected murine neocortical development by accelerating neuronal differentiation/migration, resulting in abnormal neocortical architecture as well as aberrant thalamocortical connections in the brains of adult mice. The aim of this study was to investigate whether prenatal and lactational BPA exposure affected behavior in adult mice. Pregnant mice were injected subcutaneously with 20μg/kg of BPA daily from embryonic day 0 (E0) until postnatal day 21 (P21). Control animals received a vehicle alone. Behavioral tests (n=15-20) were conducted at postnatal 3weeks (P3W) and P10-15W. After an open-field test, an elevated plus maze and Morris water maze tests were performed. The total distance in the elevated plus maze test at P3W and in the open-field test at P10W was significantly decreased in the BPA-exposed group, compared with the control group. Significant sex differences were observed in the time spent in the central area in the open-field test at P3W and in the total distance in the elevated plus maze test at P11W. These results indicated that prenatal and lactational BPA exposure disturbed the murine behavior in the postnatal development period and the adult mice. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Glow discharge based device for solving mazes

Energy Technology Data Exchange (ETDEWEB)

Dubinov, Alexander E., E-mail: dubinov-ae@yandex.ru; Mironenko, Maxim S.; Selemir, Victor D. [Russian Federal Nuclear Center − All-Russian Scientific and Research Institute of Experimental Physics (RFNC-VNIIEF), Sarov, Nizhni Novgorod region 607188 (Russian Federation); Sarov Institute of Physics and Technology (SarFTI) of National Research Nuclear University “MEPhI,” Sarov, Nizhni Novgorod region 607188 (Russian Federation); Maksimov, Artem N.; Pylayev, Nikolay A. [Russian Federal Nuclear Center − All-Russian Scientific and Research Institute of Experimental Physics (RFNC-VNIIEF), Sarov, Nizhni Novgorod region 607188 (Russian Federation)

2014-09-15

A glow discharge based device for solving mazes has been designed and tested. The device consists of a gas discharge chamber and maze-transformer of radial-azimuth type. It allows changing of the maze pattern in a short period of time (within several minutes). The device has been tested with low pressure air. Once switched on, a glow discharge has been shown to find the shortest way through the maze from the very first attempt, even if there is a section with potential barrier for electrons on the way. It has been found that ionization waves (striations) can be excited in the maze along the length of the plasma channel. The dependancy of discharge voltage on the length of the optimal path through the maze has been measured. A reduction in discharge voltage with one or two potential barriers present has been found and explained. The dependency of the magnitude of discharge ignition voltage on the length of the optimal path through the maze has been measured. The reduction of the ignition voltage with the presence of one or two potential barriers has been observed and explained.

The effects of the administration of two different doses of manganese on short-term spatial memory and anxiety-like behavior in rats

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Hogas M.

2011-01-01

Full Text Available Manganese is a very well known neurotoxic agent. It has been mainly linked to impaired motor skills and disturbed psychomotor development. However, very few aspects are known about the cognitive deficits and behavioral consequences of chronic manganese exposure. In this context, we report herein our findings regarding short-term spatial memory, motor and anxiety-like behavior assessments in male Wistar rats exposed for 45 days to two different doses (3 mg/kg b.w., i.p. and 10 mg/kg b.w., i.p. of manganese. Behavior testing (Y-maze task and elevated plus maze was performed after 45 days of manganese administration. Chronic manganese exposure in Wistar rats led to behavioral alterations consisting of cognitive deficiencies in the Y-maze task and anxiety/compulsive-like behaviors in the elevated plus maze, but no motor disturbances as tested by the number of arm entries in the Y-maze. Additional work is necessary to understand the longterm effects of different doses and dosing regimens of manganese on cognitive/affective and motor functioning.

Model testing of a 10-kg high explosive blast attenuation maze

International Nuclear Information System (INIS)

Bacigalupi, C.M.; Burton, W.A.

1981-01-01

The basement area of the proposed High Explosive Applications Facility (HEAF) at the Lawrence Livermore National Laboratory includes 10-kg HE assembly and process cells, and a 10-kg corridor for the transport of up to 10 kg of HE from the receiving dock to the cells and to the experimental firing tanks. Previous model experiments developed a process cell-maze configuration that attenuated the effects of an accidental 10-kg detonation to acceptable levels (maximum of 10 to 11 psi reflected). This document reports 1/8-scale model tests conducted to confirm the maze design and to determine the blast pressures in adjacent areas in the final HEAF building configuration. In addition, pressure/time information was obtained at selected points in the model expansion chamber to provide the architect-engineer with information for structural design

Individual differences in circadian locomotor parameters correlate with anxiety- and depression-like behavior.

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Jeffrey Anyan

Full Text Available Disrupted circadian rhythms are a core feature of mood and anxiety disorders. Circadian rhythms are coordinated by a light-entrainable master clock located in the suprachiasmatic nucleus. Animal models of mood and anxiety disorders often exhibit blunted rhythms in locomotor activity and clock gene expression. Interestingly, the changes in circadian rhythms correlate with mood-related behaviours. Although animal models of depression and anxiety exhibit aberrant circadian rhythms in physiology and behavior, it is possible that the methodology being used to induce the behavioral phenotype (e.g., brain lesions, chronic stress, global gene deletion affect behavior independently of circadian system. This study investigates the relationship between individual differences in circadian locomotor parameters and mood-related behaviors in healthy rats. The circadian phenotype of male Lewis rats was characterized by analyzing wheel running behavior under standard 12h:12h LD conditions, constant dark, constant light, and rate of re-entrainment to a phase advance. Rats were then tested on a battery of behavioral tests: activity box, restricted feeding, elevated plus maze, forced swim test, and fear conditioning. Under 12h:12h LD conditions, percent of daily activity in the light phase and variability in activity onset were associated with longer latency to immobility in the forced swim test. Variability in onset also correlated positively with anxiety-like behavior in the elevated plus maze. Rate of re-entrainment correlated positively with measures of anxiety in the activity box and elevated plus maze. Lastly, we found that free running period under constant dark was associated with anxiety-like behaviors in the activity box and elevated plus maze. Our results provide a previously uncharacterized relationship between circadian locomotor parameters and mood-related behaviors in healthy rats and provide a basis for future examination into circadian clock

[Change of hippocampal NMDA receptor and emotional behavior and spatial learning and memory in status epilepticus rat model].

Science.gov (United States)

Wang, Wei-Ping; Lou, Yan; Li, Zhen-Zhong; Li, Pan; Duan, Rui-Sheng

2007-02-01

SD rats were utilized for the purpose of the exploration of effects of status epilepticus (SE) on their emotional behavior, spatial learning and memory, and explorating its molecular mechanism. Forty maturity male SD rats, weighing (200 +/- 20) g were divided randomly and equally into SE group (SG) and normal control group (NG). The SG rats were induced by Pentylenetetrazole (PTZ) and the control animals received a saline (0.9%) solution. The change of emotional behavior in two groups were tested in elevated plus maze. Furthermore, Morris water maze was applied to evaluate the effects by SE on spatial learning and memory in rats. At the same time, N-methyl-D-aspartate (NMDA) receptor NR1 subunit mRNA in the hippocampus was determined by reverse transcription polymerase chain reaction (RT-PCR). In elevated plus test, SE rats increased the times of visits as well as the time spent on the open arms of the elevated plus maze (P emotional behavior and damage of spatial learning and memory in rats. NR1 might be involved in the patho- and physiological process in causing these behavioral changes.

Anxiolytic-like effect of Sonchus oleraceus L. in mice.

Science.gov (United States)

Cardoso Vilela, Fabiana; Soncini, Roseli; Giusti-Paiva, Alexandre

2009-07-15

Sonchus oleraceus L. has been used as a general tonic in Brazilian folk medicine. Nevertheless, available scientific information regarding this species is scarce; there are no reports related to its possible effect on the central nervous system. This study was conducted to establish the anxiolytic effect of extracts from the aerial parts of Sonchus oleraceus. This study evaluated the effect of hydroethanolic and dichloromethane extracts of Sonchus oleraceus in mice submitted to the elevated plus-maze and open-field tests. Clonazepam was used as the standard drug. In the elevated plus-maze test, the Sonchus oleraceus extracts increased the percentage of open arm entries (PSonchus oleraceus extract exerts an anxiolytic-like effect on mice.

Anxiogenic effects of chronic exposure to nandrolone decanoate (ND) at supraphysiological dose in rats: a brief report.

Science.gov (United States)

Rosic, Gvozden; Joksimovic, Jovana; Selakovic, Dragica; Milovanovic, Dragan; Jakovljevic, Vladimir

2014-01-01

Nandrolone decanoate (ND) is frequently used anabolic androgenic steroid (AAS) among the athletes. Despite the health risks, there is significant increase in prevalence of AAS abuse. The aim of this study was to investigate the effects of chronic exposure to ND at supraphysiological dose (to mimic the doses for human AAS abusers) on anxiety levels in adult rats. We performed several behavioral tests (open field test, elevated plus maze test, beam-walking test, evoked beam-walking test and tail suspension test) for estimation of anxiety in rats. Adult rats received 20 mg/kg intraperitoneal injection of ND weekly for four weeks. Behavioral test were performed on the seventh day after the last dose of ND. Anxiogenic-like pattern of behavior was clearly observed in several behavioral tests, such as open field test (decrease of total distance moved and cumulative duration of moving, decrease of an average velocity of the animals, decrease of frequency and total time in centre zone); elevated plus maze (decreased total time spent in open arms and the number of entries in open arms of the elevated plus maze); evoked beam-walking test (decreased time to cross the beam) and tail suspension test (increased latency to first immobility and decreased total duration of immobility). Results of this study show that four-week treatment with the supraphysiological dose of ND produced anxiogenic effects in sedentary male rats. Our results show that rats after chronic treatment with a supraphysiological dose of ND exhibited anxiety-like behavior.

Anthriscus nemorosa essential oil inhalation prevents memory impairment, anxiety and depression in scopolamine-treated rats.

Science.gov (United States)

Bagci, Eyup; Aydin, Emel; Ungureanu, Eugen; Hritcu, Lucian

2016-12-01

Anthriscus nemorosa (Bieb.) Sprengel is used for medicinal purposes in traditional medicine around the world, including Turkey. Ethnobotanical studies suggest that Anthriscus essential oil could improve memory in Alzheimer's disease. The current study was hypothesized to investigate the beneficial effects of inhaled Anthriscus nemorosa essential oil on memory, anxiety and depression in scopolamine-treated rats. Anthriscus nemorosa essential oil was administered by inhalation in the doses of 1% and 3% for 21 continuous days and scopolamine (0.7mg/kg) was injected intraperitoneally 30min before the behavioral testing. Y-maze and radial arm-maze tests were used for assessing memory processes. Also, the anxiety and depressive responses were studied by elevated plus-maze and forced swimming tests. As expected, the scopolamine alone-treated rats exhibited the following: decrease the percentage of the spontaneous alternation in Y-maze test, increase the number of working and reference memory errors in radial arm-maze test, decrease of the exploratory activity, the percentage of the time spent and the number of entries in the open arm within elevated plus-maze test and decrease of swimming time and increase of immobility time within forced swimming test. However, dual scopolamine and Anthriscus nemorosa essential oil-treated rats showed significant improvement of memory formation and exhibited anxiolytic- and antidepressant-like effects in scopolamine-treated rats. These results suggest that Anthriscus nemorosa essential oil inhalation can prevent scopolamine-induced memory impairment, anxiety and depression. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Perinatal exposure to genistein, a soy phytoestrogen, improves spatial learning and memory but impairs passive avoidance learning and memory in offspring.

Science.gov (United States)

Kohara, Yumi; Kuwahara, Rika; Kawaguchi, Shinichiro; Jojima, Takeshi; Yamashita, Kimihiro

2014-05-10

This study investigated the effects of perinatal genistein (GEN) exposure on the central nervous system of rat offspring. Pregnant dams orally received GEN (1 or 10 mg/kg/day) or vehicle (1 ml/kg/day) from gestation day 10 to postnatal day 14. In order to assess the effects of GEN on rat offspring, we used a battery of behavioral tests, including the open-field, elevated plus-maze, MAZE and step-through passive avoidance tests. MAZE test is an appetite-motivation test, and we used this mainly for assessing spatial learning and memory. In the MAZE test, GEN groups exhibited shorter latency from start to goal than the vehicle-treated group in both sexes. On the other hand, performances in the step-through passive avoidance test were non-monotonically inhibited by GEN in both sexes, and a significant difference was observed in low dose of the GEN-treated group compared to the vehicle-treated group in female rats. Furthermore, we found that perinatal exposure to GEN did not significantly alter locomotor activity or emotionality as assessed by the open-field and elevated-plus maze tests. These results suggest that perinatal exposure to GEN improved spatial learning and memory of rat offspring, but impaired their passive avoidance learning and memory. Copyright © 2014 Elsevier Inc. All rights reserved.

Nootropic activity of Celastrus paniculatus seed.

Science.gov (United States)

Bhanumathy, M; Harish, M S; Shivaprasad, H N; Sushma, G

2010-03-01

The effect of Celastrus paniculatus Willd. (Celastraceae) seed aqueous extract on learning and memory was studied using elevated plus maze and passive avoidance test (sodium nitrite induced amnesia rodent model). The aqueous seed extract was administered orally in two different doses to rats (350 and 1050 mg/kg) and to mice (500 and 1500 mg/kg). The results were compared to piracetam (100 mg/kg, p.o.) used as a standard drug. Chemical hypoxia was induced by subcutaneous administration of sodium nitrite (35 mg/kg), immediately after acquisition training. In elevated plus maze and sodium nitrite-induced amnesia model, Celastrus paniculatus extract has showed statistically significant improvement in memory process when compared to control. The estimation of acetylcholinesterase enzyme in rat brain supports the plus maze and passive avoidance test by reducing acetylcholinesterase activity which helps in memory performance. The study reveals that the aqueous extract of Celastrus paniculatus seed has dose-dependent cholinergic activity, thereby improving memory performance. The mechanism by which Celastrus paniculatus enhances cognition may be due to increased acetylcholine level in rat brain.

Possible antidepressant effects of vanillin against experimentally induced chronic mild stress in rats

Directory of Open Access Journals (Sweden)

Amira M. Abo-youssef

2016-06-01

Full Text Available Vanillin is a flavoring agent widely used in food and beverages such as chocolates and dairy products and it is also used to mask unpleasant tastes in medicine. It has been reported to have antioxidant, anti-inflammatory and antiapoptotic properties. The current study was designed to investigate the protective effects of vanillin against experimentally induced stress in rats. Briefly rats were subdivided into four groups. Three groups were subjected to chronic mild stress and the fourth group served as normal control group. One week before induction of stress drugs or saline was administered daily and continued for another nine weeks. At the end of the experimental period behavioral tests including sucrose preference test, forced swim test and elevated plus maze test were assessed. In addition, brain biochemical parameters including MDA, GSH, NO and serotonin were determined. Vanillin succeeded to restore the behavioral and biochemical changes associated with stress. It significantly increased sucrose consumption in sucrose preference test and time spent in open arm in elevated plus maze test as compared to stress control group. It also reduced immobility time in forced swim test and time spent in closed arm in elevated plus maze test. Additionally, it significantly decreased brain MDA and NO levels and significantly increased brain GSH and Serotonin levels compared to stress control group. It could be concluded that vanillin showed beneficial protective effects against experimentally induced stress in rats.

Anxiolytic-like effect of Carvacrol (5-isopropyl-2-methylphenol) in mice: involvement with GABAergic transmission.

Science.gov (United States)

Melo, Francisca Helvira Cavalcante; Venâncio, Edith Teles; de Sousa, Damião Pergentino; de França Fonteles, Marta Maria; de Vasconcelos, Silvânia Maria Mendes; Viana, Glauce Socorro Barros; de Sousa, Francisca Cléa Florenço

2010-08-01

Carvacrol (5-isopropyl-2-methylphenol) is a monoterpenic phenol present in the essencial oil of many plants. It is the major component of the essential oil fraction of oregano and thyme. This work presents the behavioral effects of carvacrol in animal models of elevated plus maze (EPM), open field, Rotarod and barbiturate-induced sleeping time tests in mice. Carvacrol (CVC) was administered orally, in male mice, at single doses of 12.5; 25 and 50 mg/kg while diazepam 1 or 2 mg/kg was used as standard drug and flumazenil (2.5 mg/kg) was used to elucidate the possible anxiolytic mechanism of CVC on the plus maze test. The results showed that CVC, at three doses, had no effect on the spontaneous motor activity in the Rotarod test nor in the number of squares crossed in the open-field test. However, CVC decreased the number of groomings in the open-field test. In the plus maze test, CVC, at three doses significantly increased all the observed parameters in the EPM test and flumazenil was able to reverse the effects of diazepam and CVC. Therefore, CVC did not alter the sleep latency and sleeping time in the barbiturate-induced sleeping time test. These results show that CVC presents anxiolytic effects in the plus maze test which are not influenced by the locomotor activity in the open-field test.

Anxiolytic-like effects of ursolic acid in mice.

Science.gov (United States)

Colla, André R S; Rosa, Julia M; Cunha, Mauricio P; Rodrigues, Ana Lúcia S

2015-07-05

Ursolic acid is a pentacyclic triterpenoid that possesses several biological and neuropharmacological effects including antidepressant-like activity. Anxiety disorders represent common and disability psychiatric conditions that are often associated with depressive symptoms. This work investigated the anxiolytic-like effects of ursolic acid administration in different behavioral paradigms that evaluate anxiety in mice: open field test, elevated plus maze test, light/dark box test and marble burying test. To this end, mice were administered with ursolic acid (0.1, 1 and 10mg/kg, p.o.) or diazepam (2mg/kg, p.o.), positive control, and submitted to the behavioral tests. The results show that ursolic acid (10mg/kg) elicited an anxiolytic-like effect observed by the increased total time in the center and decreased number of rearings responses in the open field test and an increased percentage of entries and total time spent in the open arms of elevated plus maze, similarly to diazepam. No significant effects of ursolic acid were shown in the light/dark box and marble burying test. These data indicate that ursolic acid exhibits anxiolytic-like effects in the open field and elevated plus maze test, but not in the light/dark box and marble burying test, showing the relevance of testing several behavioral paradigms in the evaluation of anxiolytic-like actions. Of note, the results extend the understanding on the effects of ursolic acid in the central nervous system and suggest that it may be a novel approach for the management of anxiety-related disorders. Copyright © 2015. Published by Elsevier B.V.

Navigating to new frontiers in behavioral neuroscience: Traditional neuropsychological tests predict human performance on a rodent-inspired radial-arm maze

Directory of Open Access Journals (Sweden)

Sarah E. Mennenga

2014-09-01

Full Text Available We constructed an 11-arm, walk-through, human radial-arm maze (HRAM as a translational instrument to compare existing methodology in the areas of rodent and human learning and memory research. The HRAM, utilized here, serves as an intermediary test between the classic rat radial-arm maze (RAM and standard human neuropsychological and cognitive tests. We show that the HRAM is a useful instrument to examine working memory ability, explore the relationships between rodent and human memory and cognition models, and evaluate factors that contribute to human navigational ability. One-hundred-and-fifty-seven participants were tested on the HRAM, and scores were compared to performance on a standard cognitive battery focused on episodic memory, working memory capacity, and visuospatial ability. We found that errors on the HRAM increased as working memory demand became elevated, similar to the pattern typically seen in rodents, and that for this task, performance appears similar to Miller’s classic description of human working memory capacity of 7±2 items. Regression analysis revealed that measures of working memory capacity and visuospatial ability accounted for a large proportion of variance in HRAM scores, while measures of episodic memory and general intelligence did not serve as significant predictors of HRAM performance. We present the HRAM as a novel instrument for measuring navigational behavior in humans, as is traditionally done in basic science studies evaluating rodent learning and memory, thus providing a useful tool to help connect and translate between human and rodent models of cognitive functioning.

A comparison of various methods of blood sampling in mice and rats: Effects on animal welfare

DEFF Research Database (Denmark)

Harikrishnan, Vs; Hansen, Axel K; Abelson, Klas Sp

2018-01-01

-puncture activity and anxiety levels of rats and mice were measured using an elevated plus maze test and an open field test. Stress levels 24 h post-puncture were assessed by analysing faecal corticosteroid metabolites. Sucrose intake and faecal corticosteroid levels were not affected by the blood sampling...... procedures. Rats showed reduced activity in the open field test and an increased level of anxiety in the elevated plus maze test following retrobulbar plexus puncture and isoflurane anaesthesia. In mice, nest building activity was affected in all the groups compared with the control group, except for animals...... subjected to facial vein puncture. Retrobulbar sinus puncture, tail vein puncture and sublingual puncture in mice resulted in reduced activity and increased anxiety. We conclude that, of the tested methods, puncture of the tail vein and the sublingual vein have the least adverse effects in rats, whereas...

Attenuation of ethanol abstinence-induced anxiety- and depressive-like behavior by the phosphodiesterase-4 inhibitor rolipram in rodents.

Science.gov (United States)

Gong, Mei-Fang; Wen, Rui-Ting; Xu, Ying; Pan, Jian-Chun; Fei, Ning; Zhou, Yan-Meng; Xu, Jiang-Ping; Liang, Jian-Hui; Zhang, Han-Ting

2017-10-01

Withdrawal symptoms stand as a core feature of alcohol dependence. Our previous results have shown that inhibition of phosphodiesterase-4 (PDE4) decreased ethanol seeking and drinking in alcohol-preferring rodents. However, little is known about whether PDE4 is involved in ethanol abstinence-related behavior. The objective of this study was to characterize the role of PDE4 in the development of anxiety- and depressive-like behavior induced by abstinence from ethanol exposure in different animal models. Using three rodent models of ethanol abstinence, we examined the effects of rolipram, a prototypical, selective PDE4 inhibitor, on (1) anxiety-like behavior induced by repeated ethanol abstinence in the elevated plus maze test in fawn-hooded (FH/Wjd) rats, (2) anxiety-like behavior in the open-field test and light-dark transition test following acute ethanol abstinence in C57BL/6J mice, and (3) anxiety- and depressive-like behavior induced by protracted ethanol abstinence in the elevated plus maze, forced-swim, and tail-suspension tests in C57BL/6J mice. Pretreatment with rolipram (0.1 or 0.2 mg/kg) significantly increased entries and time spent in the open arms of the elevated plus maze test in rats with repeated ethanol abstinence. Similarly, in mice with acute ethanol abstinence, administration of rolipram (0.25 or 0.5 mg/kg) dose-dependently increased the crossings in the central zone of the open-field test and duration and transitions on the light side of the light-dark transition test, suggesting anxiolytic-like effects of rolipram. Consistent with these, chronic treatment with rolipram (0.1, 0.3, or 1.0 mg/kg) increased entries in the open arms of the elevated plus maze test; it also reduced the increased duration of immobility in both the forced-swim and tail-suspension tests in mice after protracted ethanol abstinence, suggesting antidepressant-like effects of rolipram. These results provide the first demonstration for that PDE4 plays a role in modulating

Anti-Anxiety Effect of (-)-Syringaresnol-4-O-β-d-apiofuranosyl-(1→2)-β-d-glucopyranoside from Albizzia julibrissin Durazz (Leguminosae).

Science.gov (United States)

Liu, Jie; Lv, Yue-Wei; Shi, Jin-Li; Ma, Xiao-Jie; Chen, Yi; Zheng, Zhi-Quan; Wang, Sheng-Nan; Guo, Jian-You

2017-08-11

Albizzia julibrissin Durazz, a Chinese Medicine, is commonly used for its anti-anxiety effects. (-)-syringaresnol-4- O -β-d-apiofuranosyl-(1→2)-β-d-glucopyranoside (SAG) is the main ingredient of Albizzia julibrissin Durazz. The present study investigated the anxiolytic effect and potential mechanisms on the HPA axis and monoaminergic systems of SAG on acute restraint-stressed rats. The anxiolytic effect of SAG was examined through an open field test and an elevated plus maze test. The concentration of CRF, ACTH, and CORT in plasma was examined by an enzyme-linked immune sorbent assay (ELISA) kit while neurotransmitters in the cerebral cortex and hippocampus of the brain were examined by High Performance Liquid Chromatography (HPLC). We show that repeated treatment with SAG (3.6 mg/kg, p.o.) significantly increased the number and time spent on the central entries in the open-field test when compared to the vehicle/stressed group. In the elevated plus maze test, 3.6 mg/kg SAG could increase the percentage of entries into and time spent on the open arms of the elevated plus maze. In addition, the concentration of CRF, ACTH, and CORT in plasma and neurotransmitters (NE, 5-HT, DA and their metabolites 5-HIAA, DOPAC, and HVA) in the cerebral cortex and hippocampus of the brain were decreased after SAG treatment, as compared to the repeated acute restraint-stressed rats. These results suggest that SAG is a potential anti-anxiety drug candidate.

Anti-HIV drugs nevirapine and efavirenz affect anxiety-related behavior and cognitive performance in mice.

Science.gov (United States)

Romão, Pedro R T; Lemos, Joelson C; Moreira, Jeverson; de Chaves, Gisele; Moretti, Morgana; Castro, Adalberto A; Andrade, Vanessa M; Boeck, Carina R; Quevedo, João; Gavioli, Elaine C

2011-01-01

Nevirapine (NVP) and efavirenz (EFV) belong to the class of anti-HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), commonly used as part of highly active antiretroviral therapy (HAART). Although the HAART is able to bring down viral load to undetectable levels and restore immune function, their prolonged use causes several adverse effects. It has been demonstrated that both NVP and EFV are able to cross the blood-brain barrier, causing important central nervous system-related side effects. Thus, this study investigated the effects of chronic administration of EFV (10 mg/kg) and NVP (3.3 mg/kg) in mice submitted to two distinct series of experiments, which aimed to evaluate: (1) the emotional behavior (elevated plus-maze, forced swimming, and open-field test) and (2) the cognitive performance (object recognition and inhibitory avoidance test) of mice. Our results demonstrated that EFV, but not NVP, reduced the exploration to open arms in the elevated plus-maze test. Neither NVP nor EFV altered mouse behavior in the forced swimming and open-field tests. Both drugs reduced the recognition index in the object recognition test, but only EFV significantly impaired the aversive memory assessed in the inhibitory avoidance test 24 h after training. In conclusion, our findings point to a genuine anxiogenic-like effect to EFV, since it reduced exploration to open arms of elevated plus-maze test without affecting spontaneous locomotion. Additionally, both drugs impaired recognition memory, while only the treatment with EFV impaired significantly aversive memory.

Anti-anxiety effect of methanol extract of Pericarpium zanthoxyli ...

African Journals Online (AJOL)

Purpose: To determine if the methanol extract of Pericarpium zanthoxyli exerts anti-anxiety effects and also to explore any probable anti-anxiety mechanism in vivo. Methods: The staircase test, elevated plus maze test, rota-rod treadmill test and convulsions induced by strychnine and picrotoxin on mice were tested to identify ...

The selective serotonin reuptake inhibitor, escitalopram, enhances inhibition of prepotent responding and spatial reversal learning

Science.gov (United States)

Brown, Holden D.; Amodeo, Dionisio A.; Sweeney, John A.; Ragozzino, Michael E.

2011-01-01

Previous findings indicate treatment with a selective serotonin reuptake inhibitor (SSRI) facilitates behavioral flexibility when conditions require inhibition of a learned response pattern. The present experiment investigated whether acute treatment with the SSRI, escitalopram, affects behavioral flexibility when conditions require inhibition of a naturally-biased response pattern (elevated conflict test) and/or reversal of a learned response pattern (spatial reversal learning). An additional experiment was carried out to determine whether escitalopram, at doses that affected behavioral flexibility, also reduced anxiety as tested in the elevated plus-maze. In each experiment, Long-Evans rats received an intraperitoneal injection of either saline or escitalopram (0.03, 0.3 or 1.0 mg/kg) 30 minutes prior to behavioral testing. Escitalopram, at all doses tested, enhanced acquisition in the elevated conflict test, but did not affect performance in the elevated plus-maze. Escitalopram (0.3 and 1.0 mg/kg) did not alter acquisition of the spatial discrimination, but facilitated reversal learning. In the elevated conflict and spatial reversal learning test, escitalopram enhanced the ability to maintain the relevant strategy after being initially selected. The present findings suggest that enhancing serotonin transmission with a SSRI facilitates inhibitory processes when conditions require a shift away from either a naturally-biased response pattern or a learned choice pattern. PMID:22219222

Behavioral interactions of simvastatin and fluoxetine in tests of anxiety and depression

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Santos T

2012-10-01

Full Text Available Tainaê Santos,1 Monaliza Marizete Baungratz,1 Suellen Priscila Haskel,2 Daniela Delwing de Lima,3 Júlia Niehues da Cruz,4 Débora Delwing Dal Magro,5 José Geraldo Pereira da Cruz51Department of Medicine, 2Department of Physiotherapy, Regional University of Blumenau, Santa Catarina, Brazil; 3Department of Pharmacy, University of Joinville Region, Santa Catarina, Brazil; 4Department of Medicine, University of the Extreme South of Santa Catarina, Santa Catarina, Brazil; 5Department of Natural Sciences, Regional University of Blumenau, Santa Catarina, BrazilAbstract: Simvastatin inhibits 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway, and is widely used to control plasma cholesterol levels and prevent cardiovascular disease. However, emerging evidence indicates that the beneficial effects of simvastatin extend to the central nervous system. The effects of simvastatin combined with fluoxetine provide an exciting and potential paradigm to decreased anxiety and depression. Thus, the present paper investigates the possibility of synergistic interactions between simvastatin and fluoxetine in models of anxiety and depression. We investigated the effects of subchronically administered simvastatin (1 or 10 mg/kg/day combined with fluoxetine (2 or 10 mg/kg at 24, 5, and 1 hour on adult rats before conducting behavioral tests. The results indicate that simvastatin and/or fluoxetine treatment reduces anxiety-like behaviors in the elevated plus-maze and open-field tests. Our results showed that simvastatin and/or fluoxetine induced a significant increase in the swimming activity during the forced swimming test (antidepressant effect, with a concomitant increase in climbing time in simvastatin-treated animals only (noradrenergic activation. We hypothesize that anxiolytic and antidepressant effects of simvastatin and/or fluoxetine produce their behavioral effects through similar mechanisms and provide

Role of APOE Isoforms in the Pathogenesis of TBI induced Alzheimer’s Disease

Science.gov (United States)

2016-10-01

gene networks correlated to the traits (age / injury / genotype) in response to TBI. The results clearly demonstrate segregation by injury status...7 7. Participants & Other Collaborating Organizations….……………...…8 8. Figures ……………………………………………………………………10 1 1...entire maze is raised 40 cm off the ground . The elevated plus maze tests anxiety-related behavior by utilizing rodent’s fear of open and elevated

Ameliorative effect of the hydroethanolic whole plant extract of ...

African Journals Online (AJOL)

At the end of the study, biochemical markers of nitrosative and oxidative stress status were determined. Results: DH (12.5, 50 and 100 mg/kg) significantly ameliorated haloperidol-induced catalepsy (bar test), spontaneous motor and working memory deficits (open field and elevated plus maze tests, respectively), ...

Anti-anxiety effect of methanol extract of Pericarpium zanthoxyli ...

African Journals Online (AJOL)

the elevated plus maze test, suggesting that it has significant anti-anxiety activity. Furthermore, the ... Kyung-Dong Oriental Market, Seoul, Republic of. Korea. They were ... on which the mouse placed all four paws; rearing was defined as each ...

Administering ketoconazole (25mg/Kg) For 14 Days in male wistar ...

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studies conducted on the effects of stress on immune responses) ... effect) and anxiety at elevated plus-maze test. [15]. ... with 0.4 megapixel digital camera built into the microscope .... thymus at any age can be reversed, and the thymus can ...

Barnes Maze Procedure for Spatial Learning and Memory in Mice.

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Pitts, Matthew W

2018-03-05

The Barnes maze is a dry-land based rodent behavioral paradigm for assessing spatial learning and memory that was originally developed by its namesake, Carol Barnes. It represents a well-established alternative to the more popular Morris Water maze and offers the advantage of being free from the potentially confounding influence of swimming behavior. Herein, the Barnes maze experimental setup and corresponding procedures for testing and analysis in mice are described in detail.

Neuroprotective and Antiamnesic Effects of Mitragyna inermis Willd (Rubiaceae on Scopolamine-Induced Memory Impairment in Mice

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David Bougolla Pahaye

2017-01-01

Full Text Available Aim. To assess memory improvement and neuroprotective and antioxidant effects of Mitragyna inermis (M. inermis leaf decoction on the central nervous system. Methodology. Leaf decoction of M. inermis was tested on learning and memory in normal and scopolamine-induced cognitive impairment in mice using memory behavioral tests such as the Morris water maze, object recognition task, and elevated plus maze. Oxidative stress enzymes—catalase, superoxide dismutase, and the thiobarbituric acid reactive substance, a product of lipid peroxidation—were quantified. In each test, mice 18 to 25 g were divided into groups of 5. Results. The extract reversed the effects of scopolamine in mice. The extract significantly increased discrimination index in the object recognition task test and inflexion ratio in the elevated plus maze test. The times spent in target quadrant in MWM increased while the transfer latency decreased in mice treated by M. inermis at the dose of 196.5 mg/kg. The activity levels of superoxide dismutase and catalase were significantly increased, whereas the thiobarbituric acid reactive substance was significantly decreased after 8 consecutive days of treatment with M. inermis at the dose of 393 mg/kg. Conclusion. These results suggest that M. inermis leaf extract possess potential antiamnesic effects.

Hippocampal-dependent spatial memory in the water maze is preserved in an experimental model of temporal lobe epilepsy in rats.

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Marion Inostroza

Full Text Available Cognitive impairment is a major concern in temporal lobe epilepsy (TLE. While different experimental models have been used to characterize TLE-related cognitive deficits, little is known on whether a particular deficit is more associated with the underlying brain injuries than with the epileptic condition per se. Here, we look at the relationship between the pattern of brain damage and spatial memory deficits in two chronic models of TLE (lithium-pilocarpine, LIP and kainic acid, KA from two different rat strains (Wistar and Sprague-Dawley using the Morris water maze and the elevated plus maze in combination with MRI imaging and post-morten neuronal immunostaining. We found fundamental differences between LIP- and KA-treated epileptic rats regarding spatial memory deficits and anxiety. LIP-treated animals from both strains showed significant impairment in the acquisition and retention of spatial memory, and were unable to learn a cued version of the task. In contrast, KA-treated rats were differently affected. Sprague-Dawley KA-treated rats learned less efficiently than Wistar KA-treated animals, which performed similar to control rats in the acquisition and in a probe trial testing for spatial memory. Different anxiety levels and the extension of brain lesions affecting the hippocampus and the amydgala concur with spatial memory deficits observed in epileptic rats. Hence, our results suggest that hippocampal-dependent spatial memory is not necessarily affected in TLE and that comorbidity between spatial deficits and anxiety is more related with the underlying brain lesions than with the epileptic condition per se.

Behavioural profiles of two Wistar rat lines selectively bred for high or low anxiety-related behaviour.

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Liebsch, G; Montkowski, A; Holsboer, F; Landgraf, R

1998-08-01

Over the past years, two breeding lines, derived originally from outbred Wistar rats, have been established that differ markedly and consistently in their anxiety-related behaviour in the elevated plus-maze. At the age of ten weeks, rats were tested once on the elevated plus-maze and the males and females displaying the most anxious and the least anxious behaviour were sib-mated to start a new generation of the high anxiety-related behaviour (HAB) and the low anxiety-related behaviour (LAB) lines, respectively. The resulting difference in emotionality between these two lines was also evident in an open field test and correlated with differences in the forced swim test. In the open field, the HAB rats tended to be less active and explored the central zone of the open field much less than the LAB animals. In the forced swim test, HAB rats started floating earlier, spent significantly more time in this immobile posture and struggled less than LAB rats. However, in an olfactory-cued social discrimination task there was no difference between male and female animals from either line. The overall performance in these various behavioural tests suggests that selective breeding has resulted in rat lines not only differing markedly in their innate anxiety-related behaviour in the plus-maze, but also in other stress-related behavioural performances, suggesting a close link between the emotional evaluation of a novel and stressful situation and an individual's coping strategy.

Evaluating spatial memory function in mice: a within-subjects comparison between the water maze test and its adaptation to dry land.

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Llano Lopez, L; Hauser, J; Feldon, J; Gargiulo, P A; Yee, B K

2010-05-01

The Morris water maze (WM) is a common spatial memory test in rats. It has been adapted for evaluating genetic manipulations in mice. One major acknowledged problem of this cross-species translation is floating. We investigated here in mice the feasibility and practicality of an alternative paradigm-the cheeseboard (CB), which is a dry version of the WM, in a within-subject design allowing direct comparison with the conventional WM. Under identical task demands (reference or working memory), mice learned in the CB as efficiently as in the WM. Furthermore, individual differences in learning rate correlated between the two reference memory tests conducted separately in the two mazes. However, no such correlation was found with respect to reference memory retention or working memory performance. This study demonstrated that the CB is an effective alternative to the WM as spatial cognition test. Additional tests in the CB confirmed that the mice relied on extra maze cues in their spatial search. We would recommend the CB as a valuable addition to, rather than a replacement of the WM in phenotyping transgenic mice, because the two apparatus might diverge in the ability to detect individual differences in various domains of mnemonic functions.

Hydraulic laboratory testing of Sontek-IQ Plus

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Fulford, Janice M.; Kimball, Scott

2015-11-10

The SonTek-IQ Plus (IQ Plus) is a bottom-mounted Doppler instrument used for the measurement of water depth and velocity. Evaluation testing of the IQ Plus was performed to assess the accuracy of water depth, discharge, and velocity measurements. The IQ Plus met the manufacturer’s specifications and the U.S. Geological Survey (USGS) standard for depth accuracy measurement when the unit was installed, according to the manufacturer’s instructions, at 0 degrees pitch and roll. However, because of the limited depth testing conducted, the depth measurement is not recommended as a primary stage measurement. The IQ Plus was tested in a large indoor tilting flume in a 5-foot (ft) wide, approximately 2.3-ft deep section with mean velocities of 0.5, 1, 2, and 3 ft per second. Four IQ Plus instruments using firmware 1.52 tested for water-discharge accuracy using SonTek’s “theoretical” discharge method had a negative bias of -2.4 to -11.6 percent when compared with discharge measured with a SonTek FlowTracker and the midsection discharge method. The IQ Pluses with firmware 1.52 did not meet the manufacturer’s specification of +/-1 percent for measuring velocity. Three IQ Pluses using firmware 1.60 and SonTek’s “theoretical” method had a difference of -1.6 to -7.9 percent when compared with discharge measured with a SonTek FlowTracker and the midsection method. Mean-velocity measurements with firmware 1.60 met the manufacturer’s specification and Price Type AA meter accuracy requirements when compared with FlowTracker measurements. Because of the instrument’s velocity accuracy, the SonTek-IQ Plus with firmware 1.60 is considered acceptable for use as an index velocity instrument for the USGS. The discharge computed by the SonTek-IQ Plus during the tests had a substantial negative bias and will not be as accurate as a discharge computed with the index velocity method. The USGS does not recommend the use of undocumented computation methods, such as Son

Anxiety-like behavior as an early endophenotype in the TgF344-AD rat model of Alzheimer's disease.

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Pentkowski, Nathan S; Berkowitz, Laura E; Thompson, Shannon M; Drake, Emma N; Olguin, Carlos R; Clark, Benjamin J

2018-01-01

Alzheimer's disease (AD) is characterized by progressive cognitive decline and the presence of aggregates of amyloid beta (plaques) and hyperphosphorylated tau (tangles). Early diagnosis through neuropsychological testing is difficult due to comorbidity of symptoms between AD and other types of dementia. As a result, there is a need to identify the range of behavioral phenotypes expressed in AD. In the present study, we utilized a transgenic rat (TgF344-AD) model that bears the mutated amyloid precursor protein as well as presenilin-1 genes, resulting in progressive plaque and tangle pathogenesis throughout the cortex. We tested young adult male and female TgF344-AD rats in a spatial memory task in the Morris water maze and for anxiety-like behavior in the elevated plus-maze. Results indicated that regardless of sex, TgF344-AD rats exhibited increased anxiety-like behavior in the elevated plus-maze, which occurred without significant deficits in the spatial memory. Together, these results indicate that enhanced anxiety-like behavior represents an early-stage behavioral marker in the TgF344-AD rat model. Copyright © 2017 Elsevier Inc. All rights reserved.

Central and peripheral administration of antisense oligonucleotide targeting amyloid-β protein precursor improves learning and memory and reduces neuroinflammatory cytokines in Tg2576 (AβPPswe) mice.

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Farr, Susan A; Erickson, Michelle A; Niehoff, Michael L; Banks, William A; Morley, John E

2014-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease. Currently, there are no therapies to stop or reverse the symptoms of AD. We have developed an antisense oligonucleotide (OL-1) against the amyloid-β protein precursor (AβPP) that can decrease AβPP expression and amyloid-β protein (Aβ) production. This antisense rapidly crosses the blood-brain barrier, reverses learning and memory impairments, reduces oxidative stress, and restores brain-to-blood efflux of Aβ in SAMP8 mice. Here, we examined the effects of this AβPP antisense in the Tg2576 mouse model of AD. We administered the OL-1 antisense into the lateral ventricle 3 times at 2week intervals. Seventy-two hours after the third injection, we tested learning and memory in T-maze foot shock avoidance. In the second study, we injected the mice with OL-1 antisense 3 times at 2-week intervals via the tail vein. Seventy-two hours later, we tested learning and memory T-maze, novel object recognition, and elevated plus maze. At the end of behavioral testing, brain tissue was collected. OL-1 antisense administered centrally improved acquisition and retention of T-maze foot shock avoidance. OL-1 antisense administered via tail vein improved learning and memory in both T-maze foot shock avoidance and novel object-place recognition. In the elevated plus maze, the mice which received OL-1 antisense spent less time in the open arms and had fewer entries into the open arms indicating reduced disinhibitation. Biochemical analyses reveal significant reduction of AβPP signal and a reduction of measures of neuroinflammation. The current findings support the therapeutic potential of OL-1 AβPP antisense.

Anxiolytic property of hydro-alcohol extract of Lactuca sativa and its effect on behavioral activities of mice.

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Harsha, Singapura Nagesh; Anilakumar, Kandangath Raghavan

2013-01-01

Lactuca sativa, belonging to the Asteraceae family, is a leafy vegetable known for its medicinal properties. This study aimed to understand the mechanism of Lactuca sativa extract with respect to pharmacological action.We investigated the anxiolytic effects of hydro-alcoholic extract of leaves of Lactuca sativa on mice. The behavioral tests performed on mice models to assess anti-anxiety properties were: open field test (OFT), elevated plus maze test (EPM), elevated T maze test, and marble burying test. Increased locomotor activity and time spent in the "open-arm" were observed in extract fed group. Malondialdehyde (MDA) and nitrite levels were decreased, catalase and glutathione levels were increased in Lactuca sativa treated mice. The data obtained in the present study suggests that the extract of Lactuca sativa can afford significant protection against anxiolytic activity.

Teste de labirinto: instrumento de análise na aquisição de uma habilidade motora Maze test: instrument for analyzing the acquisition of motor skills

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DE Souza

2006-09-01

Full Text Available CONTEXTO: A análise da aquisição de uma habilidade motora através de instrumento simples e fácil pode auxiliar no diagnóstico e no tratamento fisioterapêutico. OBJETIVO: O estudo se propôs a verificar se o teste de labirinto pode ser utilizado como um instrumento de análise na aquisição de uma habilidade motora, através de medidas, tais como, tempo de execução e número de tentativas para estabilizar o desempenho, sob a influência de pistas visuais. MÉTODO: A amostra consistiu de 70 estudantes universitários saudáveis do sexo masculino, de 20 ± 2 anos, divididos em dois grupos que fizeram testes de labirinto com e sem pistas visuais. Foram realizadas 30 tentativas e dois testes de retenção. Os dados foram analisados pela ANOVA two-way de medidas repetidas (Newman-Keuls post hoc. RESULTADOS: Verificou-se diferença significativa no tempo de execução entre as tentativas com estabilização do desempenho a partir da 8ª tentativa no labirinto sem pistas e da 6ª tentativa no labirinto com pistas, se mantendo após os testes de retenção. No teste de labirinto com pistas a estabilização ocorreu mais cedo e o tempo de execução do movimento foi maior. CONCLUSÕES: As evidências encontradas mostraram que o teste de labirinto permite identificar a quantidade adequada de prática para treinar uma habilidade motora e verificar a influência da pista visual na estabilização do desempenho, sugerindo um instrumento a ser utilizado na FisioterapiaBACKGROUND: Analysis of the acquisition of motor skills by means of a simple and easily used instrument may assist in physiotherapeutic diagnosis and treatment. OBJECTIVE: To verify whether the maze test can be used as an instrument for analyzing the acquisition of motor skills, by means of measurements such as the time taken and number of attempts required for performance stabilization, under the influence of visual clues. METHOD: The sample consisted of 70 healthy male university

Unbiased classification of spatial strategies in the Barnes maze.

Science.gov (United States)

Illouz, Tomer; Madar, Ravit; Clague, Charlotte; Griffioen, Kathleen J; Louzoun, Yoram; Okun, Eitan

2016-11-01

Spatial learning is one of the most widely studied cognitive domains in neuroscience. The Morris water maze and the Barnes maze are the most commonly used techniques to assess spatial learning and memory in rodents. Despite the fact that these tasks are well-validated paradigms for testing spatial learning abilities, manual categorization of performance into behavioral strategies is subject to individual interpretation, and thus to bias. We have previously described an unbiased machine-learning algorithm to classify spatial strategies in the Morris water maze. Here, we offer a support vector machine-based, automated, Barnes-maze unbiased strategy (BUNS) classification algorithm, as well as a cognitive score scale that can be used for memory acquisition, reversal training and probe trials. The BUNS algorithm can greatly benefit Barnes maze users as it provides a standardized method of strategy classification and cognitive scoring scale, which cannot be derived from typical Barnes maze data analysis. Freely available on the web at http://okunlab.wix.com/okunlab as a MATLAB application. eitan.okun@biu.ac.ilSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A Preclinical Study of Casein Glycomacropeptide as a Dietary Intervention for Acute Mania

DEFF Research Database (Denmark)

Liebenberg, Nico; Jensen, Erik; Larsen, Erik Roj

2018-01-01

orally at 2, 4, or 8 h or for 1 week chronically. Amino acid and monoamine levels were measured in plasma and brain and behavior was assessed in the amphetamine-hyperlocomotion, forced swim, prepulse inhibition, and elevated plus maze tests. Results: Casein glycomacropeptide induced a time...

Behavioral characterization of CD36 knockout mice with SHIRPA primary screen.

Science.gov (United States)

Zhang, Shuxiao; Wang, Wei; Li, Juan; Cheng, Ke; Zhou, Jingjing; Zhu, Dan; Yang, Deyu; Liang, Zihong; Fang, Liang; Liao, Li; Xie, Peng

2016-02-15

CD36 is a member of the class B scavenger receptor family of cell surface proteins, which plays a major role in fatty acid, glucose and lipid metabolism. Besides, CD36 functions as a microglial surface receptor for amyloid beta peptide. Regarding this, we suggest CD36 might also contribute to neuropsychiatric disease. The aim of this study was to achieve a behavioral phenotype of CD36 knockout (CD36(-/-)) mice. We characterized the behavior of CD36(-/-) mice and C57BL/6J mice by subjecting them to a series of tests, which include SHIRPA primary behavioral screen test, 1% sucrose preference test, elevated plus-maze test, open-field test and forced swimming test. The results showed that CD36(-/-) mice traversed more squares, emitted more defecation, exhibited higher tail elevation and had more aggressive behaviors than C57BL/6J mice. The CD36(-/-) mice spent more time and traveled longer distance in periphery zone in the open-field test. Meanwhile, the numbers that CD36(-/-) mice entered in the open arms of elevated plus-maze were reduced. These findings suggest that CD36(-/-) mice present an anxious phenotype and might be involved in neuropsychiatric disorders. Copyright © 2015. Published by Elsevier B.V.

Hippocampal-dependent memory in the plus-maze discriminative avoidance task: The role of spatial cues and CA1 activity.

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Leão, Anderson H F F; Medeiros, André M; Apolinário, Gênedy K S; Cabral, Alícia; Ribeiro, Alessandra M; Barbosa, Flávio F; Silva, Regina H

2016-05-01

The plus-maze discriminative avoidance task (PMDAT) has been used to investigate interactions between aversive memory and an anxiety-like response in rodents. Suitable performance in this task depends on the activity of the basolateral amygdala, similar to other aversive-based memory tasks. However, the role of spatial cues and hippocampal-dependent learning in the performance of PMDAT remains unknown. Here, we investigated the role of proximal and distal cues in the retrieval of this task. Animals tested under misplaced proximal cues had diminished performance, and animals tested under both misplaced proximal cues and absent distal cues could not discriminate the aversive arm. We also assessed the role of the dorsal hippocampus (CA1) in this aversive memory task. Temporary bilateral inactivation of dorsal CA1 was conducted with muscimol (0.05 μg, 0.1 μg, and 0.2 μg) prior to the training session. While the acquisition of the task was not altered, muscimol impaired the performance in the test session and reduced the anxiety-like response in the training session. We also performed a spreading analysis of a fluorophore-conjugated muscimol to confirm selective inhibition of CA1. In conclusion, both distal and proximal cues are required to retrieve the task, with the latter being more relevant to spatial orientation. Dorsal CA1 activity is also required for aversive memory formation in this task, and interfered with the anxiety-like response as well. Importantly, both effects were detected by different parameters in the same paradigm, endorsing the previous findings of independent assessment of aversive memory and anxiety-like behavior in the PMDAT. Taken together, these findings suggest that the PMDAT probably requires an integration of multiple systems for memory formation, resembling an episodic-like memory rather than a pure conditioning behavior. Furthermore, the concomitant and independent assessment of emotionality and memory in rodents is relevant to

An old test for new neurons: refining the Morris water maze to study the functional relevance of adult hippocampal neurogenesis

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Alexander eGarthe

2013-05-01

Full Text Available The Morris water maze represents the de-facto standard for testing hippocampal function in laboratory rodents. In the field of adult hippocampal neurogenesis, however, using this paradigm to assess the functional relevance of the new neurons yielded surprisingly inconsistent results. While some authors found aspects of water maze performance to be linked to adult neurogenesis, others obtained different results or could not demonstrate any effect of manipulating adult neurogenesis.In this review we discuss evidence that the large diversity of protocols and setups used is an important aspect in interpreting the differences in the results that have been obtained. Even simple parameters such as pool size, number and configuration of visual landmarks, or number of trials can become highly relevant for getting the new neurons involved at all. Sets of parameters are often chosen with implicit or explicit concepts in mind and these might lead to different views on the function of adult-generated neurons.We propose that the classical parameters usually used to measure spatial learning performance in the water maze might not be particularly well suited to sensitively and specifically detect the supposedly highly specific functional changes elicited by the experimental modulation of adult hippocampal neurogenesis. As adult neurogenesis is supposed to affect specific aspects of information processing only in the hippocampus, any claim for a functional relevance of the new neurons has to be based on hippocampus-specific parameters. We also placed a special emphasis on the fact that the DG facilitates the differentiation between contexts as opposed to just differentiating places.In conclusion, while the Morris water maze has proven to be one of the most effective testing paradigms to assess hippocampus-dependent spatial learning, new and more specific questions ask for new parameters. Therefore, the full potential of the water maze task remains to be tapped.

Disentangling the cognitive components supporting Austin Maze performance in left versus right temporal lobe epilepsy.

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Hocking, Julia; Thomas, Hannah J; Dzafic, Ilvana; Williams, Rebecca J; Reutens, David C; Spooner, Donna M

2013-12-01

Neuropsychological tests requiring patients to find a path through a maze can be used to assess visuospatial memory performance in temporal lobe pathology, particularly in the hippocampus. Alternatively, they have been used as a task sensitive to executive function in patients with frontal lobe damage. We measured performance on the Austin Maze in patients with unilateral left and right temporal lobe epilepsy (TLE), with and without hippocampal sclerosis, compared to healthy controls. Performance was correlated with a number of other neuropsychological tests to identify the cognitive components that may be associated with poor Austin Maze performance. Patients with right TLE were significantly impaired on the Austin Maze task relative to patients with left TLE and controls, and error scores correlated with their performance on the Block Design task. The performance of patients with left TLE was also impaired relative to controls; however, errors correlated with performance on tests of executive function and delayed recall. The presence of hippocampal sclerosis did not have an impact on maze performance. A discriminant function analysis indicated that the Austin Maze alone correctly classified 73.5% of patients as having right TLE. In summary, impaired performance on the Austin Maze task is more suggestive of right than left TLE; however, impaired performance on this visuospatial task does not necessarily involve the hippocampus. The relationship of the Austin Maze task with other neuropsychological tests suggests that differential cognitive components may underlie performance decrements in right versus left TLE. © 2013.

Lacosamide reduces HDAC levels in the brain and improves memory: Potential for treatment of Alzheimer's disease.

Science.gov (United States)

Bang, Shraddha R; Ambavade, Shirishkumar D; Jagdale, Priti G; Adkar, Prafulla P; Waghmare, Arun B; Ambavade, Prashant D

2015-07-01

Lacosamide, a histone deacetylase (HDAC) inhibitor, has been approved for the treatment of epilepsy. Some HDAC inhibitors have been proven effective for the treatment of memory disorders. The present investigation was designed to evaluate the effect of lacosamide on memory and brain HDAC levels. The effect on memory was evaluated in animals with scopolamine-induced amnesia using the elevated plus maze, object recognition test, and radial arm maze. The levels of acetylcholinesterase and HDAC in the cerebral cortex were evaluated. Lacosamide at doses of 10 and 30mg/kg significantly reduced the transfer latency in the elevated plus maze. Lacosamide at a dose of 30mg/kg significantly increased the time spent with a familiar object in the object recognition test at the 24h interval and decreased the time spent in the baited arm. Moreover, at this dose, the number of errors in the radial arm maze at 3 and 24h intervals was minimized and a reduction in the level of HDAC1, but not acetylcholinesterase, was observed in the cerebral cortex. These effects of lacosamide are equivalent to those of piracetam at a dose of 300mg/kg. These results suggest that lacosamide at a 30mg/kg dose improves disrupted memory, possibly by inhibiting HDAC, and could be used to treat amnesic symptoms of Alzheimer's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

A novel heterocyclic compound improves working memory in the radial arm maze and modulates the dopamine receptor D1R in frontal cortex of the Sprague-Dawley rat.

Science.gov (United States)

Hussein, Ahmed M; Aher, Yogesh D; Kalaba, Predrag; Aher, Nilima Y; Dragačević, Vladimir; Radoman, Bojana; Ilić, Marija; Leban, Johann; Beryozkina, Tetyana; Ahmed, Abdel Baset M A; Urban, Ernst; Langer, Thierry; Lubec, Gert

2017-08-14

A series of compounds have been shown to enhance cognitive function via the dopaminergic system and indeed the search for more active and less toxic compounds is continuing. It was therefore the aim of the study to synthetise and test a novel heterocyclic compound for cognitive enhancement in a paradigm for working memory. Specific and effective dopamine re-uptake inhibition DAT (IC50=4,1±0,8μM) made us test this compound in a radial arm maze (RAM) in the rat. CE-125 (4-((benzhydrylsulfinyl)methyl)-2-cyclopropylthiazole), was tested for dopamine (DAT), serotonin and norepinephrine re-uptake inhibition by a well-established system. The working memory index (WMI) was evaluated in male Sprague Dawley rats that were intraperitoneally injected with CE-125 (1 or 10mg/kg body weight). In order to evaluate basic neurotoxicity, the open field, elevated plus maze, rota rod studies and the forced swim test were carried out. Frontal cortex was taken at the last day of the RAM test and dopamine receptors D1R and D2R, DAT and phosphorylated DAT protein levels were determined. On the 10th day both doses were increasing the WMI as compared to the vehicle-treated group. In both, trained and treated groups, D1R levels were significantly reduced while D2R levels were unchanged. DAT levels were comparable between all groups while phosphorylated DAT levels were increased in the trained group treated with 1mg/kg body weight. CE-125 as a probably non-neurotoxic compound and specific reuptake inhibitor was shown to increase performance (WMI) and modulation of the dopaminergic system is proposed as a possible mechanism of action. Copyright © 2017. Published by Elsevier B.V.

Genetic Testing: MedlinePlus Health Topic

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... Your Family's Health (National Institutes of Health) - PDF Topic Image MedlinePlus Email Updates Get Genetic Testing updates ... testing and your cancer risk Karyotyping Related Health Topics Birth Defects Genetic Counseling Genetic Disorders Newborn Screening ...

Influências do ciclo estral sobre o desempenho de ratos no labirinto em cruz elevado

OpenAIRE

Amauri Gouveia Júnior; Silvio Morato

2002-01-01

The Elevated plus maze is one of the most popular models to study animal anxiety. Anxiety can be influenced by physiological factors, such as the hormonal state. The aim of the present work is to investigate the relationship between estrus cycle and rat exploratory behavior in the elevated plus maze. The study made use of male (n = 13) and female rats (n = 61). The females had their estral phase identified and were divided into 3 groups according to their hormonal state: Proestrus (N = 23), E...

Stimulus-dependent changes of extracellular glucose in the rat hippocampus determined by in vivo microdialysis.

Science.gov (United States)

Rex, A; Bert, B; Fink, H; Voigt, J-P

2009-10-19

Neuronal activity is tightly coupled with brain energy metabolism; and glucose is an important energy substrate for neurons. The present in vivo microdialysis study was aimed at investigating changes in extracellular glucose concentrations in the rat ventral hippocampus due to exposure to the elevated plus maze. Determination of basal hippocampal glucose and lactate/pyruvate ratio in male Wistar rats was conducted in the home cage using in vivo microdialysis. Rats were exposed to the elevated plus maze, a rodent model of anxiety-related behaviour, or to unspecific stress induced by white noise (95dB) as a control condition. Basal hippocampal levels of glucose, as determined by zero-net-flux, and the basal lactate/pyruvate ratio were 1.49+/-0.05mmol/l and 13.8+/-1.1, respectively. In rats without manipulation, glucose levels remained constant throughout the experiment (120min). By contrast, exposure to the elevated plus maze led to a temporary decline in hippocampal glucose (-33.2+/-4.4%) which returned to baseline level in the home cage. White noise caused only a non-significant decrease in extracellular glucose level (-9.3+/-3.5%). In all groups, the lactate/pyruvate ratio remained unchanged by the experimental procedures. Our microdialysis study demonstrates that exposure to the elevated plus maze induces a transient decrease in extracellular hippocampal glucose concentration. In contrast, an unspecific stimulus did not change hippocampal glucose. The latter suggests that only specific behavioural stimuli increase hippocampal glucose utilization in the ventral hippocampus.

Effect of clozapine on locomotor activity and anxiety-related behavior in the neonatal mice administered MK-801.

Science.gov (United States)

Pınar, Neslihan; Akillioglu, Kubra; Sefil, Fatih; Alp, Harun; Sagir, Mustafa; Acet, Ahmet

2015-08-11

Atypical antipsychotics have been used to treat fear and anxiety disturbance that are highly common in schizophrenic patients. It is suggested that disruptions of N-methyl-d-aspartate (NMDA)-mediated transmission of glutamate may underlie the pathophysiology of schizophrenia. The present study was conducted to analyze the effectiveness of clozapine on the anxiety-related behavior and locomotor function of the adult brain, which had previously undergone NMDA receptor blockade during a developmental period. In order to block the NMDA receptor, male mice were administered 0.25 mg/kg of MK-801 on days 7 to 10 postnatal. In adulthood, they were administered intraperitoneally 0.5 mg/kg of clozapine and tested with open-field and elevated plus maze test, to assess their emotional behavior and locomotor activity. In the group receiving MK-801 in the early developmental period the elevated plus maze test revealed a reduction in the anxiety-related behavior (ptest indicated a decrease in locomotor activity (plocomotor activity and anxiety-related behavior, induced by administration of the MK-801 in neonatal period.

Electric Current Solves Mazes

Science.gov (United States)

Ayrinhac, Simon

2014-01-01

We present in this work a demonstration of the maze-solving problem with electricity. Electric current flowing in a maze as a printed circuit produces Joule heating and the right way is instantaneously revealed with infrared thermal imaging. The basic properties of electric current can be discussed in this context, with this challenging question:…

Development of locomotor activity of rat pups in figure-eight mazes.

Science.gov (United States)

Ruppert, P H; Dean, K F; Reiter, L W

1985-05-01

In a series of four experiments, social and experiential factors that influence the development of motor activity in rat pups were examined. Motor activity was monitored from postnatal Days 13 to 21 as photocell interruptions in figure-eight mazes and comparisons were made between pups maintained in a nest box containing a dam and siblings and allowed access to the maze for 23 hr/day, pups tested daily for 1 hr/day vs pups tested only on postnatal Days 15, 18, or 21, pups tested daily for either 5 min, 30 min, or 1 hr/day, and pups tested daily for 30 min/day either singly in a maze, paired with a littermate, or paired with an anesthetized pup of the same age. A monotonic increase in activity was seen for nest-box testing, minimal developmental change was seen for pups tested on only a single day or for pups tested with an anesthetized pup, whereas all other groups showed an inverted U-shaped profile of activity which was influenced by the duration of testing and/or the presence of a littermate. These data emphasize the relevance of environmental factors as determinants of preweaning behavior.

Water Associated Zero Maze: A novel rat test for long term traumatic re-experiencing

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Gilad eRitov

2014-01-01

Full Text Available Often, freezing and startle behaviors in the context of a previously experienced stress are taken as an indication of posttraumatic stress disorder (PTSD-like symptoms in rats. However, PTSD is characterized by large individual variations of symptoms. In order to take into consideration the complex and long term distinctive variations in effects of trauma exposure additional behavioral measures are required.The current study used a novel behavioral test, the Water Associated Zero Maze (WAZM. This test was planned to enable a formation of an association between the context of the maze and an underwater trauma or swim stress in order to examine the impact of exposure to the context which immediately precedes a stressful or a traumatic experience on rat's complex behavior. Rats were exposed to the WAZM and immediately after to an underwater trauma or short swim. One month later rats were re-exposed to the context of the WAZM while their behavior was video recorded. Furthermore, c-Fos expression in the amygdala was measured 90 min after this exposure.The results of the current study indicate that the WAZM can be used to discern behavioral changes measured a long time after the actual traumatic or stressful events. Furthermore, the behavioral changes detected were accompanied by changes of c-Fos expression in the amygdala of exposed rats. We suggest that the WAZM can be used to model traumatic memories re-experiencing in rodent models of human stress-related pathologies such as PTSD.

Transgenic mice expressing constitutive active MAPKAPK5 display gender-dependent differences in exploration and activity

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Moens Ugo

2007-11-01

Full Text Available Abstract Background The mitogen-activated protein kinases, MAPKs for short, constitute cascades of signalling pathways involved in the regulation of several cellular processes that include cell proliferation, differentiation and motility. They also intervene in neurological processes like fear conditioning and memory. Since little remains known about the MAPK-Activated Protein Kinase, MAPKAPK5, we constructed the first MAPKAPK knockin mouse model, using a constitutive active variant of MAPKAPK5 and analyzed the resulting mice for changes in anxiety-related behaviour. Methods We performed primary SHIRPA observations during background breeding into the C57BL/6 background and assessed the behaviour of the background-bred animals on the elevated plus maze and in the light-dark test. Our results were analyzed using Chi-square tests and homo- and heteroscedatic T-tests. Results Female transgenic mice displayed increased amounts of head dips and open arm time on the maze, compared to littermate controls. In addition, they also explored further into the open arm on the elevated plus maze and were less active in the closed arm compared to littermate controls. Male transgenic mice displayed no differences in anxiety, but their locomotor activity increased compared to non-transgenic littermates. Conclusion Our results revealed anxiety-related traits and locomotor differences between transgenic mice expressing constitutive active MAPKAPK5 and control littermates.

Rolling block mazes are PSPACE-complete

NARCIS (Netherlands)

Buchin, K.; Buchin, M.

2012-01-01

In a rolling block maze, one or more blocks lie on a rectangular board with square cells. In most mazes, the blocks have size k × m × n where k, m, n are integers that determine the size of the block in terms of units of the size of the board cells. The task of a rolling block maze is to roll a

Protective effect of curcumin (Curcuma longa), against aluminium toxicity: Possible behavioral and biochemical alterations in rats.

Science.gov (United States)

Kumar, Anil; Dogra, Samrita; Prakash, Atish

2009-12-28

Aluminium is a potent neurotoxin and has been associated with Alzheimer's disease (AD) causality for decades. Prolonged aluminium exposure induces oxidative stress and increases amyloid beta levels in vivo. Current treatment modalities for AD provide only symptomatic relief thus necessitating the development of new drugs with fewer side effects. The aim of the study was to demonstrate the protective effect of chronic curcumin administration against aluminium-induced cognitive dysfunction and oxidative damage in rats. Aluminium chloride (100 mg/kg, p.o.) was administered to rats daily for 6 weeks. Rats were concomitantly treated with curcumin (per se; 30 and 60 mg/kg, p.o.) daily for a period of 6 weeks. On the 21st and 42nd day of the study behavioral studies to evaluate memory (Morris water maze and elevated plus maze task paradigms) and locomotion (photoactometer) were done. The rats were sacrificed on 43rd day following the last behavioral test and various biochemical tests were performed to assess the extent of oxidative damage. Chronic aluminium chloride administration resulted in poor retention of memory in Morris water maze, elevated plus maze task paradigms and caused marked oxidative damage. It also caused a significant increase in the acetylcholinesterase activity and aluminium concentration in aluminium treated rats. Chronic administration of curcumin significantly improved memory retention in both tasks, attenuated oxidative damage, acetylcholinesterase activity and aluminium concentration in aluminium treated rats (Paluminium-induced cognitive dysfunction and oxidative damage.

Cholinergic Modulation of Restraint Stress Induced Neurobehavioral ...

African Journals Online (AJOL)

The involvement of the cholinergic system in restraint stress induced neurobehavioral alterations was investigated in rodents using the hole board, elevated plus maze, the open field and the light and dark box tests. Restraint stress (3h) reduced significantly (p<0.05) the number of entries and time spent in the open arm, ...

Blood Count Tests: MedlinePlus Health Topic

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... Spanish WBC count (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Blood Count Tests ... WBC count Show More Show Less Related Health Topics Bleeding Disorders Blood Laboratory Tests National Institutes of ...

Effects of Amphetamine and β-Endorphin Fragments on Maze Performance in Rats

NARCIS (Netherlands)

Boer, S. de; Bohus, B.

1990-01-01

Fragments of β-endorphin and amphetamine cause similar effects in some tests of maze behavior in rats. The present study served to compare the influence of amphetamine and two β-endorphin fragments [β-endorphin (βE)-(2-9) and βE-(2-16)] on maze behavior in more detail. In Experiment I no significant

Anxiolytic-like effects of erythrinian alkaloids from Erythrina suberosa

Energy Technology Data Exchange (ETDEWEB)

Serrano, Maria Amelia R.; Batista, Andrea N. de L.; Bolzani, Vanderlan da S.; Santos, Luciana de A. [UNESP, Araraquara, SP (Brazil). Inst. de Quimica; Nogueira, Paulo J. de C.; Nunes-de-Souza, Ricardo L. [UNESP, Araraquara, SP (Brazil). Faculdade de Ciencias Farmaceuticas; Latif, Abdul; Arfan, Mohammad [University of Peshawar, Peshawar (Pakistan). Inst. of Chemical Sciences

2011-07-01

Two alkaloids, erysodine (1) and erysothrine (2) were isolated from the flowers of a Pakistani medicinal plant, Erythrina suberosa. These compounds were investigated for anxiolytic properties, and the results showed significant effect, in an acute oral treatment with 1-2, which were suspended in saline (NaCl 0.9%) plus DMSO 1%, and evaluated in 122 Swiss male mice exposed to two tests of anxiety - the elevated plus-maze (EPM) and the light/dark transition model (LDTM). (author)

Anxiolytic-like effects of erythrinian alkaloids from Erythrina suberosa

International Nuclear Information System (INIS)

Serrano, Maria Amelia R.; Batista, Andrea N. de L.; Bolzani, Vanderlan da S.; Santos, Luciana de A.; Nogueira, Paulo J. de C.; Nunes-de-Souza, Ricardo L.; Latif, Abdul; Arfan, Mohammad

2011-01-01

Two alkaloids, erysodine (1) and erysothrine (2) were isolated from the flowers of a Pakistani medicinal plant, Erythrina suberosa. These compounds were investigated for anxiolytic properties, and the results showed significant effect, in an acute oral treatment with 1-2, which were suspended in saline (NaCl 0.9%) plus DMSO 1%, and evaluated in 122 Swiss male mice exposed to two tests of anxiety - the elevated plus-maze (EPM) and the light/dark transition model (LDTM). (author)

Antinociceptive and Anxiolytic and Sedative Effects of Methanol Extract of Anisomeles indica: An Experimental Assessment in Mice and Computer Aided Models

OpenAIRE

Md. Josim Uddin; A. S. M. Ali Reza; Md. Abdullah-Al-Mamun; Mohammad S. H. Kabir; Mst. Samima Nasrin; Sharmin Akhter; Md. Saiful Islam Arman; Md. Atiar Rahman

2018-01-01

Anisomeles indica (L.) kuntze is widely used in folk medicine against various disorders including allergy, sores, inflammation, and fever. This research investigated the antinociceptive, anxiolytic and sedative effects of A. indica methanol extract. The antinociceptive activity was assessed with the acetic acid-induced writhing test and formalin-induced flicking test while sedative effects with open field and hole cross tests and anxiolytic effects with elevated plus maze (EPM) and thiopental...

Kidney Tests: MedlinePlus Health Topic

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... Spanish Total protein (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Kidney Tests updates ... hour volume Show More Show Less Related Health Topics Kidney Cancer Kidney Diseases National Institutes of Health ...

Effects of chronic administration of fenproporex on cognitive and non-cognitive behaviors.

Science.gov (United States)

Gonçalves, Cinara L; Furlanetto, Camila B; Valvassori, Samira S; Bavaresco, Daniela V; Varela, Roger B; Budni, Josiane; Quevedo, João; Streck, Emilio L

2015-04-01

Fenproporex (Fen) is an amphetamine-based anorectic; amphetamine use causes a broad range of severe cognitive deficits and anxiogenic-like effects. In this study we evaluated pharmacological effects of the chronic administration of Fen on cognitive and non-cognitive behaviors. Male adult Wistar rats received intraperitoneal administration of vehicle (control group) or Fen (6.25, 12.5 or 25 mg/kg) for 14 days; the animals were then subjected to habituation and object recognition tasks in open-field apparatus, and elevated plus-maze task. The administration of Fen (12.5 and 25 mg/kg) impaired habituation during the second exposure to the habituation task. In addition, the same doses of Fen also impaired the performance in object recognition task. In elevated plus-maze task, the administration of Fen (in all doses tested) induced anxiogenic-like effects in rats. Our results suggest that chronic Fen administration alters memory and induces anxiogenic-like effects in rats.

Anti-anxiety activity of hydro alcoholic extract of Scoparia dulcis Linn. assessed using different experimental anxiety models In rodents

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Arasan Elayaraja

2015-03-01

Full Text Available Scoparia dulcis belonging to the family Scrophulariaceae is an valuable medicinal herb, had showed antiviral, antimalarial, anticancer and antidiabetic activities. The present study was aimed to investigate the anti-anxiety activity of crude ethanolic extract of S.dulcis L by various behavioural models. Preliminary phytochemical investigation revealed the presence of  phenols and flavonoids. The extract at 100mg/kg and 200mg/kg was evaluated for anti anxiety activity by  Open-field test [OFT], Elevated plus-maze test [EPM], Elevated Zero-maze test [EZM],, Social interaction test [SI] And  Novelty induced suppressed feeling latency test [FL]   and the results of behavioral tests indicated the dose dependent anti-anxiety activity of  Scoparia dulcis which is comparable to standard. It was concluded that crude ethanolic extract showed anti anxiety activity.Further studies are needed to identify the anxiolytic mechanism(s and the phytochemicals responsible for the observed anxiolytic effect  of the hydroalcoholic extract of Scoparia dulcis. 

Hippocampal activation during the recall of remote spatial memories in radial maze tasks.

Science.gov (United States)

Schlesiger, Magdalene I; Cressey, John C; Boublil, Brittney; Koenig, Julie; Melvin, Neal R; Leutgeb, Jill K; Leutgeb, Stefan

2013-11-01

Temporally graded retrograde amnesia is observed in human patients with medial temporal lobe lesions as well as in animal models of medial temporal lobe lesions. A time-limited role for these structures in memory recall has also been suggested by the observation that the rodent hippocampus and entorhinal cortex are activated during the retrieval of recent but not of remote memories. One notable exception is the recall of remote memories for platform locations in the water maze, which requires an intact hippocampus and results in hippocampal activation irrespective of the age of the memory. These findings raise the question whether the hippocampus is always involved in the recall of spatial memories or, alternatively, whether it might be required for procedural computations in the water maze task, such as for calculating a path to a hidden platform. We performed spatial memory testing in radial maze tasks to distinguish between these possibilities. Radial maze tasks require a choice between spatial locations on a center platform and thus have a lesser requirement for navigation than the water maze. However, we used a behavioral design in the radial maze that retained other aspects of the standard water maze task, such as the use of multiple start locations and retention testing in a single trial. Using the immediate early gene c-fos as a marker for neuronal activation, we found that all hippocampal subregions were more activated during the recall of remote compared to recent spatial memories. In areas CA3 and CA1, activation during remote memory testing was higher than in rats that were merely reexposed to the testing environment after the same time interval. Conversely, Fos levels in the dentate gyrus were increased after retention testing to the extent that was also observed in the corresponding exposure control group. This pattern of hippocampal activation was also obtained in a second version of the task that only used a single start arm instead of multiple

Avoidance behaviour and anxiety in rats irradiated with a sublethal dose of gamma-rays.

Science.gov (United States)

Tomášová, Lenka; Smajda, B; Bona, M

2011-12-01

The aim of this study was to assess, whether a sublethal dose of gamma-rays will influence the avoidance behaviour and anxiety in rats and whether the response to radiation depends on time of day of its application. Adult male Wistar rats were tested in elevated plus-maze, in hot plate test and in the light/dark box in 4 regular intervals during a day. After two weeks the animals were irradiated with a whole-body dose 6 Gy of gamma-rays. One day after irradiation the animals were repeatedly tested in the same way, as before irradiation. In the plus-maze test an increased level of anxiety was established. The irradiation significantly decreased the locomotor activity of rats, but the extent of exploratory and comfortable behaviour were not altered. After irradiation, an elevated aversion to the thermal stimulus was observed in the hot plate test. The effects of radiation were more pronounced in the light period of the day, than in the dark one. No significant differences in aversion to light were detected after irradiation. The obtained results indicate, that sublethal doses of ionizing radiation can markedly influence the reactivity of animals to adverse stimuli, their motoric activity and emotional status, as well.

MK-801 and memantine act differently on short-term memory tested with different time-intervals in the Morris water maze test.

Science.gov (United States)

Duda, Weronika; Wesierska, Malgorzata; Ostaszewski, Pawel; Vales, Karel; Nekovarova, Tereza; Stuchlik, Ales

2016-09-15

N-methyl-d-aspartate receptors (NMDARs) play a crucial role in spatial memory formation. In neuropharmacological studies their functioning strongly depends on testing conditions and the dosage of NMDAR antagonists. The aim of this study was to assess the immediate effects of NMDAR block by (+)MK-801 or memantine on short-term allothetic memory. Memory was tested in a working memory version of the Morris water maze test. In our version of the test, rats underwent one day of training with 8 trials, and then three experimental days when rats were injected intraperitoneally with low- 5 (MeL), high - 20 (MeH) mg/kg memantine, 0.1mg/kg MK-801 or 1ml/kg saline (SAL) 30min before testing, for three consecutive days. On each experimental day there was just one acquisition and one test trial, with an inter-trial interval of 5 or 15min. During training the hidden platform was relocated after each trial and during the experiment after each day. The follow-up effect was assessed on day 9. Intact rats improved their spatial memory across the one training day. With a 5min interval MeH rats had longer latency then all rats during retrieval. With a 15min interval the MeH rats presented worse working memory measured as retrieval minus acquisition trial for path than SAL and MeL and for latency than MeL rats. MK-801 rats had longer latency than SAL during retrieval. Thus, the high dose of memantine, contrary to low dose of MK-801 disrupts short-term memory independent on the time interval between acquisition and retrieval. This shows that short-term memory tested in a working memory version of water maze is sensitive to several parameters: i.e., NMDA receptor antagonist type, dosage and the time interval between learning and testing. Copyright © 2016. Published by Elsevier B.V.

Effects of Topical Anesthetics on Behavior, Plasma Corticosterone, and Blood Glucose Levels after Tail Biopsy of C57BL/6NHSD Mice (Mus musculus).

Science.gov (United States)

Dudley, Emily S; Johnson, Robert A; French, DeAnne C; Boivin, Gregory P

2016-01-01

Tail biopsy is a common procedure that is performed to obtain genetic material for determining genotype of transgenic mice. The use of anesthetics or analgesics is recommended, although identifying safe and effective drugs for this purpose has been challenging. We evaluated the effects of topical 2.5% lidocaine-2.5% prilocaine cream applied to the distal tail tip at 5 or 60 min before biopsy, immersion of the tail tip for 10 seconds in ice-cold 70% ethanol just prior to biopsy, and immersion of the tail tip in 0.5% bupivacaine for 30 s after biopsy. Mice were 7, 11, or 15 d old at the time of tail biopsy. Acute behavioral responses, plasma corticosterone, and blood glucose were measured after biopsy, and body weight and performance in elevated plus maze and open-field tests after weaning. Ice-cold ethanol prior to biopsy prevented acute behavioral responses to biopsy, and both ice-cold ethanol and bupivacaine prevented elevations in corticosterone and blood glucose after biopsy. Tail biopsy with or without anesthesia did not affect body weight or performance on elevated plus maze or open-field tests. We recommend the use of ice-cold ethanol for topical anesthesia prior to tail biopsy in mice 7 to 15 d old.

1-Oleoyl lysophosphatidic acid: a new mediator of emotional behavior in rats.

Directory of Open Access Journals (Sweden)

Estela Castilla-Ortega

Full Text Available The role of lysophosphatidic acid (LPA in the control of emotional behavior remains to be determined. We analyzed the effects of the central administration of 1-oleoyl-LPA (LPA 18∶1 in rats tested for food consumption and anxiety-like and depression-like behaviors. For this purpose, the elevated plus-maze, open field, Y maze, forced swimming and food intake tests were performed. In addition, c-Fos expression in the dorsal periaqueductal gray matter (DPAG was also determined. The results revealed that the administration of LPA 18∶1 reduced the time in the open arms of the elevated plus-maze and induced hypolocomotion in the open field, suggesting an anxiogenic-like phenotype. Interestingly, these effects were present following LPA 18∶1 infusion under conditions of novelty but not under habituation conditions. In the forced swimming test, the administration of LPA 18∶1 dose-dependently increased depression-like behavior, as evaluated according to immobility time. LPA treatment induced no effects on feeding. However, the immunohistochemical analysis revealed that LPA 18∶1 increased c-Fos expression in the DPAG. The abundant expression of the LPA1 receptor, one of the main targets for LPA 18∶1, was detected in this brain area, which participates in the control of emotional behavior, using immunocytochemistry. These findings indicate that LPA is a relevant transmitter potentially involved in normal and pathological emotional responses, including anxiety and depression.

"Asparagus Racemosus" Enhances Memory and Protects against Amnesia in Rodent Models

Science.gov (United States)

Ojha, Rakesh; Sahu, Alakh N.; Muruganandam, A. V.; Singh, Gireesh Kumar; Krishnamurthy, Sairam

2010-01-01

"Asparagus Racemosus" (AR) is an Ayurvedic rasayana possessing multiple neuropharmacological activities. The adpatogenic and antidepressant activity of AR is well documented. The present study was undertaken to assess nootropic and anti-amnesic activities of MAR in rats. The Morris water maze (MWM) and elevated plus maze (EPM) models were employed…

Problem-solving in English through business mazes

CERN Document Server

Farthing, Joni

1981-01-01

We choose our job carefully. What we cannot choose are our colleagues - so it's not surprising that conflict and friction can arise in our working relationships. Business Mazes presents such problems for you to solve. Follow a route through the maze ans see the outcome of each decision you make. You may find that the quickest rout isn't always the best, or the easiest, in the long run. Business Mazes is designed for intermediate and advanced level students of English, working alone or in groups. It includes full teaching plans and exercises. The mazes may also be used effectively as an interesting approach to discussion for young people preparing their first job.

[Effects of nootropic drugs on behavior of BALB/c and C57BL/6 mice in the exploratory cross-maze test].

Science.gov (United States)

Vasil'eva, E V; Salimov, R M; Kovalev, G I

2012-01-01

Exploratory behavior, locomotor activity, and anxiety in inbred mice of C57BL/6 and BALB/c strains subchronically treated with placebo or various types of nootropic (cognition enhancing) drugs (piracetam, phenotropil, noopept, semax, pantogam, nooglutil) have been evaluated using the exploratory cross-maze test. It was found that BALB/c mice in comparison to C57BL/6 mice are characterized by greater anxiety and lower efficiency of exploratory behavior in the previously unfamiliar environment. All tested drugs clearly improved the exploratory behavior in BALB/c mice only. In BALB/c mice, piracetam, phenotropil, noopept, and semax also reduced anxiety, while phenotropil additionally increased locomotor activity. Thus, the nootropic drugs displayed clear positive modulation of spontaneous orientation in the mice strain with initially low exploratory efficiency (BALB/c) in the cross-maze test. Some drugs (pantogam, nooglutil) exhibited only nootropic properties, while the other drugs exhibited both nootropic effects on the exploratory activity and produced modulation of the anxiety level (piracetam, fenotropil, noopept, semax) and locomotor activity (fenotropil).

Status epilepticus in immature rats leads to behavioural and cognitive impairment and epileptogenesis

Czech Academy of Sciences Publication Activity Database

Kubová, Hana; Mareš, Pavel; Suchomelová, Lucie; Brožek, Gustav; Druga, Rastislav; Pitkanen, A.

2004-01-01

Roč. 19, č. 12 (2004), s. 3255-3265 ISSN 0953-816X R&D Projects: GA MZd NF6474; GA ČR GA309/01/0285 Institutional research plan: CEZ:AV0Z5011922 Keywords : epilepsy * elevated plus-maze * Morris water-maze Subject RIV: FH - Neurology Impact factor: 3.820, year: 2004

A Maze Game on Android Using Growing Tree Method

Science.gov (United States)

Hendrawan, Y. F.

2018-01-01

A maze is a type of puzzle games where a player moves in complex and branched passages to find a particular target or location. One method to create a maze is the Growing Tree method. The method creates a tree that has branches which are the paths of a maze. This research explored three types of Growing Tree method implementations for maze generation on Android mobile devices. The layouts produced could be played in first and third-person perspectives. The experiment results showed that it took 17.3 seconds on average to generate 20 cells x 20 cells dynamic maze layouts.

CBM Maze-Scores as Indicators of Reading Level and Growth for Seventh-Grade Students

Science.gov (United States)

Chung, Siuman; Espin, Christine A.; Stevenson, Claire E.

2018-01-01

The technical adequacy of CBM maze-scores as indicators of reading level and growth for seventh-grade secondary-school students was examined. Participants were 452 Dutch students who completed weekly maze measures over a period of 23 weeks. Criterion measures were school level, dyslexia status, scores and growth on a standardized reading test.…

Chronic prenatal caffeine exposure impairs novel object recognition and radial arm maze behaviors in adult rats.

Science.gov (United States)

Soellner, Deborah E; Grandys, Theresa; Nuñez, Joseph L

2009-12-14

In this report, we demonstrate that chronic prenatal exposure to a moderate dose of caffeine disrupts novel object recognition and radial arm maze behaviors in adult male and female rats. Pregnant dams were administered either tap water or 75 mg/L caffeinated tap water throughout gestation. Oral self-administration in the drinking water led to an approximate maternal intake of 10mg/kg/day, equivalent to 2-3 cups of coffee/day in humans based on a metabolic body weight conversion. In adulthood, the offspring underwent testing on novel object recognition, radial arm maze, and Morris water maze tasks. Prenatal caffeine exposure was found to impair 24-h memory retention in the novel object recognition task and impair both working and reference memory in the radial arm maze. However, prenatal caffeine exposure did not alter Morris water maze performance in either a simple water maze procedure or in an advanced water maze procedure that included reversal and working memory paradigms. These findings demonstrate that chronic oral intake of caffeine throughout gestation can alter adult cognitive behaviors in rats.

Harmine treatment enhances short-term memory in old rats: Dissociation of cognition and the ability to perform the procedural requirements of maze testing.

Science.gov (United States)

Mennenga, Sarah E; Gerson, Julia E; Dunckley, Travis; Bimonte-Nelson, Heather A

2015-01-01

Harmine is a naturally occurring monoamine oxidase inhibitor that has recently been shown to selectively inhibit the dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A (DYRK1A). We investigated the cognitive effects of 1mg (low) Harmine and 5mg (high) Harmine using the delayed-match-to-sample (DMS) asymmetrical 3-choice water maze task to evaluate spatial working and recent memory, and the Morris water maze task (MM) to test spatial reference memory. Animals were also tested on the visible platform task, a water-escape task with the same motor, motivational, and reinforcement components as the other tasks used to evaluate cognition, but differing in its greater simplicity and that the platform was visible above the surface of the water. A subset of the Harmine-high treated animals showed clear motor impairments on all behavioral tasks, and the visible platform task confirmed a lack of competence to perform the procedural components of water maze testing. After excluding animals from the high dose group that could not perform the procedural components of a swim task, it was revealed that both high- and low-dose treatment with Harmine enhanced performance on the latter portion of DMS testing, but had no effect on MM performance. Thus, this study demonstrates the importance of confirming motor and visual competence when studying animal cognition, and verifies the one-day visible platform task as a reliable measure of ability to perform the procedural components necessary for completion of a swim task. Copyright © 2014. Published by Elsevier Inc.

GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior

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Fuka Aizawa

2016-12-01

Full Text Available The free fatty acid receptor 1 (GPR40/FFAR1 is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO mice. The emotional behavior in wild and KO male mice was evaluated at 9–10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC–MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain.

Progesterone protects normative anxiety-like responding among ovariectomized female mice that conditionally express the HIV-1 regulatory protein, Tat, in the CNS.

Science.gov (United States)

Paris, Jason J; Fenwick, Jason; McLaughlin, Jay P

2014-05-01

Increased anxiety is co-morbid with human immunodeficiency virus (HIV) infection. Actions of the neurotoxic HIV-1 regulatory protein, Tat, may contribute to affective dysfunction. We hypothesized that Tat expression would increase anxiety-like behavior of female GT-tg bigenic mice that express HIV-1 Tat protein in the brain in a doxycycline-dependent manner. Furthermore, given reports that HIV-induced anxiety may occur at lower rates among women, and that the neurotoxic effects of Tat are ameliorated by sex steroids in vitro, we hypothesized that 17β-estradiol and/or progesterone would ameliorate Tat-induced anxiety-like effects. Among naturally-cycling proestrous and diestrous mice, Tat-induction via 7days of doxycycline treatment significantly increased anxiety-like responding in an open field, elevated plus maze and a marble-burying task, compared to treatment with saline. Proestrous mice demonstrated less anxiety-like behavior than diestrous mice in the open field and elevated plus maze, but these effects did not significantly interact with Tat-induction. Among ovariectomized mice, doxycycline-induced Tat protein significantly increased anxiety-like behavior in an elevated plus maze and a marble burying task compared to saline-treated mice, but not an open field (where anxiety-like responding was already maximal). Co-administration of progesterone (4mg/kg), but not 17β-estradiol (0.09mg/kg), with doxycycline significantly ameliorated anxiety-like responding in the elevated plus maze and marble burying tasks. When administered together, 17β-estradiol partially antagonized the protective effects of progesterone on Tat-induced anxiety-like behavior. These findings support evidence of steroid-protection over HIV-1 proteins, and extend them by demonstrating the protective capacity of progesterone on Tat-induced anxiety-like behavior of ovariectomized female mice. Copyright © 2014 Elsevier Inc. All rights reserved.

Water spray-induced grooming is negatively correlated with depressive behavior in the forced swimming test in rats.

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Shiota, Noboru; Narikiyo, Kimiya; Masuda, Akira; Aou, Shuji

2016-05-01

Rodents show grooming, a typical self-care behavior, under stress and non-stress conditions. Previous studies revealed that grooming under stress conditions such as the open-field test (OFT) or the elevated plus-maze test (EPM) is associated with anxiety, but the roles of grooming under non-stress conditions are not well understood. Here, we examined spray-induced grooming as a model of grooming under a non-stress condition to investigate the relationship between this grooming and depression-like behavior in the forced swim test (FST) and tail suspension test, and we compared spray-induced grooming with OFT- and EPM-induced grooming. The main finding was that the duration of spray-induced grooming, but not that of OFT/EPM-induced grooming, was negatively correlated with the duration of immobility in the FST, an index of depression-like behavior. The results suggest that spray-induced grooming is functionally different from the grooming in the OFT and EPM and is related to reduction of depressive behavior.

Elevated CO2 plus chronic warming reduce nitrogen uptake and levels or activities of nitrogen-uptake and -assimilatory proteins in tomato roots.

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Jayawardena, Dileepa M; Heckathorn, Scott A; Bista, Deepesh R; Mishra, Sasmita; Boldt, Jennifer K; Krause, Charles R

2017-03-01

Atmospheric CO 2 enrichment is expected to often benefit plant growth, despite causing global warming and nitrogen (N) dilution in plants. Most plants primarily procure N as inorganic nitrate (NO 3 - ) or ammonium (NH 4 + ), using membrane-localized transport proteins in roots, which are key targets for improving N use. Although interactive effects of elevated CO 2 , chronic warming and N form on N relations are expected, these have not been studied. In this study, tomato (Solanum lycopersicum) plants were grown at two levels of CO 2 (400 or 700 ppm) and two temperature regimes (30 or 37°C), with NO 3 - or NH 4 + as the N source. Elevated CO 2 plus chronic warming severely inhibited plant growth, regardless of N form, while individually they had smaller effects on growth. Although %N in roots was similar among all treatments, elevated CO 2 plus warming decreased (1) N-uptake rate by roots, (2) total protein concentration in roots, indicating an inhibition of N assimilation and (3) shoot %N, indicating a potential inhibition of N translocation from roots to shoots. Under elevated CO 2 plus warming, reduced NO 3 - -uptake rate per g root was correlated with a decrease in the concentration of NO 3 - -uptake proteins per g root, reduced NH 4 + uptake was correlated with decreased activity of NH 4 + -uptake proteins and reduced N assimilation was correlated with decreased concentration of N-assimilatory proteins. These results indicate that elevated CO 2 and chronic warming can act synergistically to decrease plant N uptake and assimilation; hence, future global warming may decrease both plant growth and food quality (%N). © 2016 Scandinavian Plant Physiology Society.

Ablation of fast-spiking interneurons in the dorsal striatum, recapitulating abnormalities seen post-mortem in Tourette syndrome, produces anxiety and elevated grooming.

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Xu, M; Li, L; Pittenger, C

2016-06-02

Tic disorders, including Tourette syndrome (TS), are thought to involve pathology of cortico-basal ganglia loops, but their pathology is not well understood. Post-mortem studies have shown a reduced number of several populations of striatal interneurons, including the parvalbumin-expressing fast-spiking interneurons (FSIs), in individuals with severe, refractory TS. We tested the causal role of this interneuronal deficit by recapitulating it in an otherwise normal adult mouse using a combination transgenic-viral cell ablation approach. FSIs were reduced bilaterally by ∼40%, paralleling the deficit found post-mortem. This did not produce spontaneous stereotypies or tic-like movements, but there was increased stereotypic grooming after acute stress in two validated paradigms. Stereotypy after amphetamine, in contrast, was not elevated. FSI ablation also led to increased anxiety-like behavior in the elevated plus maze, but not to alterations in motor learning on the rotorod or to alterations in prepulse inhibition, a measure of sensorimotor gating. These findings indicate that a striatal FSI deficit can produce stress-triggered repetitive movements and anxiety. These repetitive movements may recapitulate aspects of the pathophysiology of tic disorders. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Validating the Electric Maze Task as a Measure of Planning

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Sheppard, Kelly W.; Cheatham, Carol L.

2017-01-01

The Electric Maze Task (EMT) is a novel planning task designed to allow flexible testing of planning abilities across a broad age range and to incorporate manipulations to test underlying planning abilities, such as working-memory and inhibitory control skills. The EMT was tested in a group of 63 typically developing 7- to 12-year-olds.…

Intelligence-Augmented Rat Cyborgs in Maze Solving.

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Yipeng Yu

Full Text Available Cyborg intelligence is an emerging kind of intelligence paradigm. It aims to deeply integrate machine intelligence with biological intelligence by connecting machines and living beings via neural interfaces, enhancing strength by combining the biological cognition capability with the machine computational capability. Cyborg intelligence is considered to be a new way to augment living beings with machine intelligence. In this paper, we build rat cyborgs to demonstrate how they can expedite the maze escape task with integration of machine intelligence. We compare the performance of maze solving by computer, by individual rats, and by computer-aided rats (i.e. rat cyborgs. They were asked to find their way from a constant entrance to a constant exit in fourteen diverse mazes. Performance of maze solving was measured by steps, coverage rates, and time spent. The experimental results with six rats and their intelligence-augmented rat cyborgs show that rat cyborgs have the best performance in escaping from mazes. These results provide a proof-of-principle demonstration for cyborg intelligence. In addition, our novel cyborg intelligent system (rat cyborg has great potential in various applications, such as search and rescue in complex terrains.

Intelligence-Augmented Rat Cyborgs in Maze Solving.

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Yu, Yipeng; Pan, Gang; Gong, Yongyue; Xu, Kedi; Zheng, Nenggan; Hua, Weidong; Zheng, Xiaoxiang; Wu, Zhaohui

2016-01-01

Cyborg intelligence is an emerging kind of intelligence paradigm. It aims to deeply integrate machine intelligence with biological intelligence by connecting machines and living beings via neural interfaces, enhancing strength by combining the biological cognition capability with the machine computational capability. Cyborg intelligence is considered to be a new way to augment living beings with machine intelligence. In this paper, we build rat cyborgs to demonstrate how they can expedite the maze escape task with integration of machine intelligence. We compare the performance of maze solving by computer, by individual rats, and by computer-aided rats (i.e. rat cyborgs). They were asked to find their way from a constant entrance to a constant exit in fourteen diverse mazes. Performance of maze solving was measured by steps, coverage rates, and time spent. The experimental results with six rats and their intelligence-augmented rat cyborgs show that rat cyborgs have the best performance in escaping from mazes. These results provide a proof-of-principle demonstration for cyborg intelligence. In addition, our novel cyborg intelligent system (rat cyborg) has great potential in various applications, such as search and rescue in complex terrains.

Curcuma comosa improves learning and memory function on ovariectomized rats in a long-term Morris water maze test

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Su, Jian; Sripanidkulchai, Kittisak; Wyss, J. Michael; Sripanidkulchai, Bungorn

2010-01-01

Aim of the study Curcuma comosa extract and some purified compounds from this plant have been reported to have estrogenic-like effects, and estrogen improves learning in some animals and potentially in postmenopausal women; therefore, this study tested the hypothesis that Curcuma comosa and estrogen have similar beneficial effects on spatial learning and memory. Materials and methods Curcuma comosa hexane extract, containing 0.165 mg of (4E,6E)-1,7-diphenylhepta-4,6-dien-3-one per mg of the crude extract, was orally administered to ovariectomized Wistar rats at the doses of 250 or 500 mg/kg body weight. 17β-estradiol (10 μg/kg body weight, subcutaneously) was used as a positive control. Thirty days after the initiation of treatment, animals were tested in a Morris water maze for spatial learning and memory. They were re-tested every 30 days and a final probe trial was run on day 119. Results Compared to control rats, OVX rats displayed significant memory impairment for locating the platform in the water maze from day 67 after the surgery, onward. In contrast, OVX rats treated with either Curcuma comosa or estrogen were significantly protected from this decline in cognitive function. Further, the protection of cognitive effects by Curcuma comosa was larger at higher dose. Conclusions These results suggest that long-term treatment with Curcuma comosa has beneficial effects on learning and memory function in rats. PMID:20420894

Sex differences in vicarious trial-and-error behavior during radial arm maze learning.

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Bimonte, H A; Denenberg, V H

2000-02-01

We investigated sex differences in VTE behavior in rats during radial arm maze learning. Females made more VTEs than males, although there were no sex differences in learning. Further, VTEs and errors were positively correlated during the latter testing sessions in females, but not in males. This sex difference may be a reflection of differences between the sexes in conflict behavior or cognitive strategy while solving the maze.

Evaluation of Anticonvulsant, Sedative, Anxiolytic, and Phytochemical Profile of the Methanol Extract from the Aerial Parts of Swertia corymbosa (Griseb. Wight ex C.B. Clarke

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G. Mahendran

2014-01-01

Full Text Available The objective of the present study was to evaluate the anxiolytic, antidepressant, and anticonvulsant activity of the methanolic extract of Swertia corymbosa (SCMeOH. After acute toxicity test, oral treatment with SCMeOH at doses of 125, 250, and 500 mg/kg behavioral models of open field, elevated-plus-maze, actophotometer, rotarod, pentylenetetrazole, isoniazid, and maximal electroshock induced seizure models were utilized. In open field test, SCMeOH (125, 250, and 500 mg/kg (P<0.01, P<0.001 increased the number of rearings. However, the number of central motor and ambulation (P<0.01, P<0.001 were reduced. Likewise, the number of entries and the time spent in open arm were increased while the number of locomotion was decreased (P<0.001 in elevated-plus-maze and actophotometer test, respectively. SCMeOH (125–500 mg/kg protected the mice against the pentylenetetrazole and isoniazid induced convulsions; it causes significant (P<0.01 and P<0.001 dose dependent increase in latency of convulsion. Treatment with SCMeOH reduced the duration of the tonic hind limb extension induced by electroshock. Two major compounds such as gentiopicroside and swertianin were analyzed by HPLC system.

Neurobehavioral and Antioxidant Effects of Ethanolic Extract of Yellow Propolis

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Cinthia Cristina Sousa de Menezes da Silveira

2016-01-01

Full Text Available Propolis is a resin produced by bees from raw material collected from plants, salivary secretions, and beeswax. New therapeutic properties for the Central Nervous System have emerged. We explored the neurobehavioral and antioxidant effects of an ethanolic extract of yellow propolis (EEYP rich in triterpenoids, primarily lupeol and β-amyrin. Male Wistar rats, 3 months old, were intraperitoneally treated with Tween 5% (control, EEYP (1, 3, 10, and 30 mg/kg, or diazepam, fluoxetine, and caffeine (positive controls 30 min before the assays. Animals were submitted to open field, elevated plus maze, forced swimming, and inhibitory avoidance tests. After behavioral tasks, blood samples were collected through intracardiac pathway, to evaluate the oxidative balance. The results obtained in the open field and in the elevated plus maze assay showed spontaneous locomotion preserved and anxiolytic-like activity. In the forced swimming test, EEYP demonstrated antidepressant-like activity. In the inhibitory avoidance test, EEYP showed mnemonic activity at 30 mg/kg. In the evaluation of oxidative biochemistry, the extract reduced the production of nitric oxide and malondialdehyde without changing level of total antioxidant, catalase, and superoxide dismutase, induced by behavioral stress. Our results highlight that EEYP emerges as a promising anxiolytic, antidepressant, mnemonic, and antioxidant natural product.

Memory-enhancing activity of Anacyclus pyrethrum in albino Wistar rats

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K Sujith

2012-08-01

Full Text Available Objective: To explore the potential effect of ethanolic extract of Anacyclus pyrethrum (A. pyrethrum in memory dysfunction. Methods: Memory impairment was produced by administration of scopolamine (1mg/kg i. p in rats. Passive avoidance paradigms, elevated plus maze and social learning task was used to assess learning and memory. Results: A. pyrethrum extract treated group decreased transfer latency in elevated plus maze model paradigm which is an indicative of cognition improvement. In case of passive avoidance paradigm extract treated group exhibited prounced effect in reversal of scopolamine induced amnesia which was revealed by increase in step down latency. Social learning task also revealed the memory enhancing activity of A. pyrethrum extract. Conclusions: Ethanolic extract of A. pyrethrum has been demonstrated to improve cognitive processes by enhancing memory in different experimental paradigms such as passive avoidance paradigms, elevated plus maze and social learning task when administered orallyBrain cholinesterase level was measured to assess central cholinergic activity. The treatment with drugs, which increase cholinergic neurotransmission, causes an improvement in cognitive deficits. The present study suggest that ethanolic extract of A. pyrethrum increased brain cholinesterase level and hence it possess memory enhancing activity in scopolamine induced amnesia model by enhancing central cholinergic neurotransmission.

Unilateral robotic hybrid mini-maze: a novel experimental approach.

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Moslemi, Mohammad; Rawashdeh, Badi; Meyer, Mark; Nguyen, Duy; Poston, Robert; Gharagozloo, Farid

2016-03-01

A complete Cox maze IV procedure is difficult to accomplish using current endoscopic and minimally invasive techniques. These techniques are hampered by inability to adequately dissect the posterior structures of the heart and place all necessary lesions. We present a novel approach, using robotic technology, that achieves placement of all the lesions of the complete maze procedure. In three cadaveric human models, the technical feasibility of using robotic instruments through the right chest to dissect the posterior structures of the heart and place all Cox maze lesions was performed. The entire posterior aspect of the heart was dissected in the cadaveric model facilitating successful placement of all Cox maze IV lesions with robotic assistance through minimally invasive incisions. The robotic Cox maze IV procedure through the novel right thoracic approach is feasible. This obviates the need for sternotomy and avoids the associated morbidity of the conventional Cox-maze procedure. Copyright © 2015 John Wiley & Sons, Ltd.

Long-term voluntary exercise prevents post-weaning social isolation-induced cognitive impairment in rats.

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Okudan, Nilsel; Belviranlı, Muaz

2017-09-30

This study aimed to determine the effect of exercise on locomotion, anxiety-related behavior, learning, and memory in socially isolated post-weaning rats, as well as the correlation between exercise and the concentration of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus. Rats were randomly assigned to three groups: the control group; the social isolation group; the social isolation plus exercise (SIE) group. Social isolation conditions, with or without exercise were maintained for 90d, and then multiple behavioral tests, including the open-field test, elevated plus maze test, and Morris water maze (MWM) test were administered. Following behavioral assessment, hippocampal tissue samples were obtained for measurement of BDNF and NGF. There wasn't a significant difference in locomotor activity between the groups (P>0.05). Anxiety scores were higher in the socially isolated group (Psocially isolated rats (Psocial isolation-induced reduction in hippocampal BDNF and NGF content (Psocially isolated post-weaning rats. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Use of an eight-arm radial water maze to assess working and reference memory following neonatal brain injury.

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Penley, Stephanie C; Gaudet, Cynthia M; Threlkeld, Steven W

2013-12-04

Working and reference memory are commonly assessed using the land based radial arm maze. However, this paradigm requires pretraining, food deprivation, and may introduce scent cue confounds. The eight-arm radial water maze is designed to evaluate reference and working memory performance simultaneously by requiring subjects to use extra-maze cues to locate escape platforms and remedies the limitations observed in land based radial arm maze designs. Specifically, subjects are required to avoid the arms previously used for escape during each testing day (working memory) as well as avoid the fixed arms, which never contain escape platforms (reference memory). Re-entries into arms that have already been used for escape during a testing session (and thus the escape platform has been removed) and re-entries into reference memory arms are indicative of working memory deficits. Alternatively, first entries into reference memory arms are indicative of reference memory deficits. We used this maze to compare performance of rats with neonatal brain injury and sham controls following induction of hypoxia-ischemia and show significant deficits in both working and reference memory after eleven days of testing. This protocol could be easily modified to examine many other models of learning impairment.

Distinction between epigenic and hypogenic maze caves

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Palmer, Arthur N.

2011-11-01

Certain caves formed by dissolution of bedrock have maze patterns composed of closed loops in which many intersecting fractures or pores have enlarged simultaneously. Their origin can be epigenic (by shallow circulation of meteoric groundwater) or hypogenic (by rising groundwater or production of deep-seated solutional aggressiveness). Epigenic mazes form by diffuse infiltration through a permeable insoluble caprock or by floodwater supplied by sinking streams. Most hypogenic caves involve deep sources of aggressiveness. Transverse hypogenic cave origin is a recently proposed concept in which groundwater of mainly meteoric origin rises across strata in the distal portions of large flow systems, to form mazes in soluble rock sandwiched between permeable but insoluble strata. The distinction between maze types is debated and is usually based on examination of diagnostic cave features and relation of caves to their regional setting. In this paper, the principles of mass transfer are applied to clarify the limits of each model, to show how cave origin is related to groundwater discharge, dissolution rate, and time. The results show that diffuse infiltration and floodwater can each form maze caves at geologically feasible rates (typically within 500 ka). Transverse hypogenic mazes in limestone, to enlarge significantly within 1 Ma, require an unusually high permeability of the non-carbonate beds (generally ≥ 10-4 cm/s), large discharge, and calcite saturation no greater than 90%, which is rare in deep diffuse flow in sedimentary rocks. Deep sources of aggressiveness are usually required. The origin of caves by transverse hypogenic flow is much more favorable in evaporite rocks than in carbonate rocks.

Evaluation of the analgesic, sedative-anxiolytic, cytotoxic and thrombolytic potentials of the different extracts of Kalanchoe pinnata leaves

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Md. Razibul Habib

2015-12-01

Full Text Available Objective: To evaluate the analgesic, neuropharmacological, cytotoxic and thrombolytic potentials of the aqueous, ethanol and ethyl acetate extracts of Kalanchoe pinnata leaves. Methods: At the dose of 400 mg/kg body weight, the analgesic activity of the extracts were evaluated by the acetic acid-induced writhing and formalin-induced persistent pain tests while neuropharmacological activity was evaluated by the open field, hole cross and elevated plus maze tests. The cytotoxic potential was observed by brine shrimp lethality bioassay and the thrombolytic potential was investigated by clot lysis test. Results: The aqueous extract significantly suppressed the number of writhing (96.78% as well as the formalin-induced persistent pain on the early phase (46.92% and on the late phase (40.98%. Again in case of hole cross and open field tests, the locomotor activity was decreased significantly (P < 0.001 mostly by the ethyl acetate extract. Furthermore, the sedative-anxiolytic activity was supported by the increased percent (P < 0.01 of frequency into the open arm on elevated plus maze test. Besides, the extracts showed moderate lethality and thrombolytic activity. Conclusions: The findings showed that activities are comparable to the standards and in some cases are stronger than the standards. Therefore, based on the results, it is evident that it has great analgesic and sedative-anxiolytic activity with moderate cytotoxic and thrombolytic potential.

Guiding brine shrimp through mazes by solving reaction diffusion equations

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Singal, Krishma; Fenton, Flavio

Excitable systems driven by reaction diffusion equations have been shown to not only find solutions to mazes but to also to find the shortest path between the beginning and the end of the maze. In this talk we describe how we can use the Fitzhugh-Nagumo model, a generic model for excitable media, to solve a maze by varying the basin of attraction of its two fixed points. We demonstrate how two dimensional mazes are solved numerically using a Java Applet and then accelerated to run in real time by using graphic processors (GPUs). An application of this work is shown by guiding phototactic brine shrimp through a maze solved by the algorithm. Once the path is obtained, an Arduino directs the shrimp through the maze using lights from LEDs placed at the floor of the Maze. This method running in real time could be eventually used for guiding robots and cars through traffic.

GPR30 activation decreases anxiety in the open field test but not in the elevated plus maze test in female mice

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Anchan, Divya; Clark, Sara; Pollard, Kevin; Vasudevan, Nandini

2014-01-01

The GPR30 is a novel estrogen receptor (ER) that is a candidate membrane ER based on its binding to 17beta estradiol and its rapid signaling properties such as activation of the extracellular-regulated kinase (ERK) pathway. Its distribution in the mouse limbic system predicts a role for this receptor in the estrogenic modulation of anxiety behaviors in the mouse. A previous study showed that chronic administration of a selective agonist to the GPR30 receptor, G-1, in the female rat can improv...

Pharmacologic Treatment Assigned for Niemann Pick Type C1 Disease Partly Changes Behavioral Traits in Wild-Type Mice.

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Schlegel, Victoria; Thieme, Markus; Holzmann, Carsten; Witt, Martin; Grittner, Ulrike; Rolfs, Arndt; Wree, Andreas

2016-11-09

Niemann-Pick Type C1 (NPC1) is an autosomal recessive inherited disorder characterized by accumulation of cholesterol and glycosphingolipids. Previously, we demonstrated that BALB/c-npc1 nih Npc1 -/- mice treated with miglustat, cyclodextrin and allopregnanolone generally performed better than untreated Npc1 -/- animals. Unexpectedly, they also seemed to accomplish motor tests better than their sham-treated wild-type littermates. However, combination-treated mutant mice displayed worse cognition performance compared to sham-treated ones. To evaluate effects of these drugs in healthy BALB/c mice, we here analyzed pharmacologic effects on motor and cognitive behavior of wild-type mice. For combination treatment mice were injected with allopregnanolone/cyclodextrin weekly, starting at P7. Miglustat injections were performed daily from P10 till P23. Starting at P23, miglustat was embedded in the chow. Other mice were treated with miglustat only, or sham-treated. The battery of behavioral tests consisted of accelerod, Morris water maze, elevated plus maze, open field and hot-plate tests. Motor capabilities and spontaneous motor behavior were unaltered in both drug-treated groups. Miglustat-treated wild-type mice displayed impaired spatial learning compared to sham- and combination-treated mice. Both combination- and miglustat-treated mice showed enhanced anxiety in the elevated plus maze compared to sham-treated mice. Additionally, combination treatment as well as miglustat alone significantly reduced brain weight, whereas only combination treatment reduced body weight significantly. Our results suggest that allopregnanolone/cyclodextrin ameliorate most side effects of miglustat in wild-type mice.

Pharmacologic Treatment Assigned for Niemann Pick Type C1 Disease Partly Changes Behavioral Traits in Wild-Type Mice

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Victoria Schlegel

2016-11-01

Full Text Available Niemann-Pick Type C1 (NPC1 is an autosomal recessive inherited disorder characterized by accumulation of cholesterol and glycosphingolipids. Previously, we demonstrated that BALB/c-npc1nihNpc1−/− mice treated with miglustat, cyclodextrin and allopregnanolone generally performed better than untreated Npc1−/− animals. Unexpectedly, they also seemed to accomplish motor tests better than their sham-treated wild-type littermates. However, combination-treated mutant mice displayed worse cognition performance compared to sham-treated ones. To evaluate effects of these drugs in healthy BALB/c mice, we here analyzed pharmacologic effects on motor and cognitive behavior of wild-type mice. For combination treatment mice were injected with allopregnanolone/cyclodextrin weekly, starting at P7. Miglustat injections were performed daily from P10 till P23. Starting at P23, miglustat was embedded in the chow. Other mice were treated with miglustat only, or sham-treated. The battery of behavioral tests consisted of accelerod, Morris water maze, elevated plus maze, open field and hot-plate tests. Motor capabilities and spontaneous motor behavior were unaltered in both drug-treated groups. Miglustat-treated wild-type mice displayed impaired spatial learning compared to sham- and combination-treated mice. Both combination- and miglustat-treated mice showed enhanced anxiety in the elevated plus maze compared to sham-treated mice. Additionally, combination treatment as well as miglustat alone significantly reduced brain weight, whereas only combination treatment reduced body weight significantly. Our results suggest that allopregnanolone/cyclodextrin ameliorate most side effects of miglustat in wild-type mice.

Psychometric Properties of Maze Tasks in Middle School Students

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Tolar, Tammy D.; Barth, Amy E.; Francis, David J.; Fletcher, Jack M.; Stuebing, Karla K.; Vaughn, Sharon

2012-01-01

Maze tasks have appealing properties as progress-monitoring tools, but there is a need for a thorough examination of the psychometric properties of Maze tasks among middle school students. We evaluated form effects, reliability, validity, and practice effects of Maze among students in Grades 6 through 8. We administered the same (familiar) and…

Ondansetron attenuates depression co-morbid with obesity in obese mice subjected to chronic unpredictable mild stress; an approach using behavioral battery tests.

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Kurhe, Yeshwant; Radhakrishnan, Mahesh; Gupta, Deepali

2014-09-01

The aim of the present work was to investigate the role of ondansetron on the high fat diet (HFD) induced obese mice for behavioral and biochemical alterations using chronic unpredictable mild stress (CUMS) model of depression. Animals were fed with high fat diet for 14 weeks and subjected to different stress procedures for 4 weeks. Treatment with ondansetron was started on day 15. After day 28 behavioral assays and biochemical estimations were performed. Behavioral paradigms viz. sucrose preference test, locomotor score, forced swim test (FST) and elevated plus maze (EPM), whereas biochemical parameters like plasma glucose, total cholesterol, triglycerides and total proteins were estimated. Results examines that in behavioral assays, ondansetron significantly (P glucose, total cholesterol, triglycerides and total proteins were significantly (P glucose level indicates that, it could be "altered glucose level" playing an important role in depression co-morbid with obesity. Ondansetron through allosteric modulation of serotonergic system elevates the serotonin level and thereby regulates the insulin secretion and hence, reversing the "altered glucose level", could be the possible antidepressive-like mechanism against depression co-morbid with obesity.

Place and Response Learning in the Open-field Tower Maze.

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Lipatova, Olga; Campolattaro, Matthew M; Toufexis, Donna J; Mabry, Erin A

2015-10-28

This protocol describes how the Open-field Tower Maze (OFTM) paradigm is used to study spatial learning in rodents. This maze is especially useful for examining how rats learn to use a place- or response-learning to successfully navigate in an open-field arena. Additionally, this protocol describes how the OFTM differs from other behavioral maze paradigms that are commonly used to study spatial learning in rodents. The OFTM described in this article was adapted from the one previously described by Cole, Clipperton, and Walt (2007). Specifically, the OFTM was created to test spatial learning in rodents without the experimenter having to consider how "stress" might play a role as a confounding variable. Experiments have shown that stress-alone can significantly affect cognitive function(1). The representative results section contains data from an experiment that used the OFTM to examine the effects of estradiol treatment on place- and response-learning in adult female Sprague Dawley rats(2). Future studies will be designed to examine the role of the hippocampus and striatum in place- and response-learning in the OFTM.

Neonatal tactile stimulation reverses the effect of neonatal isolation on open-field and anxiety-like behavior, and pain sensitivity in male and female adult Sprague-Dawley rats.

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Imanaka, A; Morinobu, S; Toki, S; Yamamoto, S; Matsuki, A; Kozuru, T; Yamawaki, S

2008-01-10

It is well known that early life events induce long-lasting psychophysiological and psychobiological influences in later life. In rodent studies, environmental enrichment after weaning prevents the adulthood behavioral and emotional disturbances in response to early adversities. We compared the behavioral effect of neonatal isolation (NI) with the effect of NI accompanied by tactile stimulation (NTS) to determine whether NTS could reverse or prevent the effects of NI on the adulthood behavioral and emotional responses to environmental stimuli. In addition, we also examined the sex difference of the NTS effect. Measurements of body weights, an open-field locomotor test, an elevated plus maze test, a hot-plate test, and a contextual fear-conditioning test were performed on postnatal day 60. As compared with rats subjected to NI, rats subjected to NTS showed significantly higher activity and exploration in the open-field locomotor test, lower anxiety-like behavior in the elevated plus maze test, and significantly prolonged latencies in the hot-plate test, and this effect was equal among males and females. In the contextual fear-conditioning test, whereas NTS significantly reduced the enhanced freezing time due to NI in females, no significant difference in the freezing time between NI and NTS was found in males. These findings indicate that adequate tactile stimulation in early life plays an important role in the prevention of disturbances in the behavioral and emotional responses to environmental stimuli in adulthood induced by early adverse experiences.

Effects of caffeine on learning and memory in rats tested in the Morris water maze

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Angelucci M.E.M.

2002-01-01

Full Text Available We studied some of the characteristics of the improving effect of the non-specific adenosine receptor antagonist, caffeine, using an animal model of learning and memory. Groups of 12 adult male Wistar rats receiving caffeine (0.3-30 mg/kg, ip, in 0.1 ml/100 g body weight administered 30 min before training, immediately after training, or 30 min before the test session were tested in the spatial version of the Morris water maze task. Post-training administration of caffeine improved memory retention at the doses of 0.3-10 mg/kg (the rats swam up to 600 cm less to find the platform in the test session, P<=0.05 but not at the dose of 30 mg/kg. Pre-test caffeine administration also caused a small increase in memory retrieval (the escape path of the rats was up to 500 cm shorter, P<=0.05. In contrast, pre-training caffeine administration did not alter the performance of the animals either in the training or in the test session. These data provide evidence that caffeine improves memory retention but not memory acquisition, explaining some discrepancies among reports in the literature.

Envolvimento de receptores 5-HT2C do hipocampo ventral em comportamentos de defesa de ratos no labirinto em cruz elevado Involvement of ventral hippocampus 5-HT2C receptors on defensive behaviors of rats in the elevated plus-maze

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Marília Greidinger Carvalho

2012-04-01

Full Text Available A ativação farmacológica dos receptores 5-HT2C induz comportamentos de defesa em modelos animais. O estudo busca investigar se o bloqueio seletivo de receptores 5-HT2C no hipocampo ventral (HV previne comportamentos defensivos induzidos por um agonista de receptor 5-HT2C administrado perifericamente em ratos expostos ao labirinto em cruz elevado (LCE. Quinze minutos após injeções intraperitoniais (IP, 1ml/kg do agonista 5-HT2C WAY-161503, ratos foram microinjetados bilateralmente no HV com o antagonista seletivo de receptores 5-HT2C SB-242084 (0, 0,1, 0,5 ou 1.5μg. Dez minutos após, cada animal foi exposto ao LCE para o registro de categorias de ansiedade. Injeções sistêmicas do WAY-161503 reduziram seletivamente as explorações nos braços abertos e aumentaram padrões de avaliação de risco. Esse efeito foi atenuado de maneira dose-dependente pela microinjeção de SB-242084 no HV, confirmando a ação ansiogênica de agonistas 5-HT2C e sugerindo que esse perfil comportamental seja mediado, pelo menos em parte, por receptores 5-HT2C do HV.Pharmacological 5-HT2C receptor activation induces defensive behaviors in several animal models of anxiety. The present study investigated whether the selective blockade of 5-HT2C receptors in the ventral hippocampus (VH prevents defensive behaviors induced by a 5-HT2C agonist administered systemically in rats exposed to the elevated plus-maze (EPM. Fifteen minutes after intraperitonial (IP, 1ml/kg injections of the selective 5-HT2C receptor agonist WAY-161503 (3 mg/kg, rats were bilaterally microinjected with the selective 5-HT2C antagonist SB-242084 (0, 0.1, 0.5 or 1.5μg into the VH. Ten minutes after, each animal was exposed to the EPM for measuring classical and ethological anxiety measures. IP WAY-161503 injections selectively decreased open-arm exploration while increasing risk-assessment. This anxiogenic-like action was dose-dependently attenuated by intra-VH SB-242084 microinjections

GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior.

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Aizawa, Fuka; Nishinaka, Takashi; Yamashita, Takuya; Nakamoto, Kazuo; Kurihara, Takashi; Hirasawa, Akira; Kasuya, Fumiyo; Miyata, Atsuro; Tokuyama, Shogo

2016-12-01

The free fatty acid receptor 1 (GPR40/FFAR1) is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO) mice. The emotional behavior in wild and KO male mice was evaluated at 9-10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC-MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Effects of the mGluR5 antagonist MPEP on ethanol withdrawal induced anxiety-like syndrome in rats.

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Kumar, Jaya; Hapidin, Hermizi; Bee, Yvonne-Tee Get; Ismail, Zalina

2013-11-26

Abstinence from chronic ethanol consumption leads to the manifestation of a variety of symptoms attributed to central nervous system hyperexcitability, such as increased irritability, anxiety, and restlessness. Recent studies have demonstrated the importance of metabotropic glutamate receptor 5 (mGluR5) in addictive behaviours. This study investigates the effects of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on ethanol withdrawal induced anxiety using two behavioural paradigms. Male Wistar rats were fed a Modified Liquid Diet (MLD) containing low fat cow milk, sucrose, and maltodextrin with a gradual introduction of 2.4%, 4.8% and 7.2% ethanol for 20 days. Six hours into ethanol withdrawal, the rats were intraperitoneally injected with normal saline and MPEP (2.5, 5.0, 10, 20, 30 mg/kg) and were assessed for ethanol withdrawal induced anxiety-like syndrome using an automated elevated plus maze and an open field. MPEP at 10 mg/kg significantly attenuated ethanol withdrawal induced anxiety without any compromising effects on locomotor activities. Despite reversing several indices of ethanol withdrawal induced anxiety in both the elevated plus maze and the open field, low doses of MPEP (2.5, 5 mg/kg) significantly compromised the locomotor activities of ethanol withdrawn rats. High doses of MPEP (20 and 30 mg/kg) significantly attenuated withdrawal anxiety when tested in the elevated plus maze but not in the open field. Administration of MPEP (2.5, 5, 10, 20, 30 mg/kg) has no significant compromising effect on the locomotor activities of ethanol naïve rats. Despite significantly reducing withdrawal anxiety in both behavioural paradigms at 10 mg/kg, the compromising effects of low and high doses of MPEP must be further explored along with the therapeutic efficiency of this drug for relieving withdrawal induced anxiety.

Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP.

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Muhia, Mary; Yee, Benjamin K; Feldon, Joram; Markopoulos, Foivos; Knuesel, Irene

2010-02-01

The brain-specific Ras/Rap-GTPase activating protein (SynGAP) is a prime candidate linking N-methyl-d-aspartate receptors to the regulation of the ERK/MAP kinase signalling cascade, suggested to be essential for experience-dependent synaptic plasticity. Here, we evaluated the behavioural phenotype of SynGAP heterozygous knockout mice (SG(+/-)), expressing roughly half the normal levels of SynGAP. In the cognitive domain, SG(+/-) mice demonstrated severe working and reference memory deficits in the radial arm maze task, a mild impairment early in the transfer test of the water maze task, and a deficiency in spontaneous alternation in an elevated T-maze. In the non-cognitive domain, SG(+/-) mice were hyperactive in the open field and appeared less anxious in the elevated plus maze test. In contrast, object recognition memory performance was not impaired in SG(+/-) mice. The reduction in SynGAP thus resulted in multiple behavioural traits suggestive of aberrant cognitive and non-cognitive processes normally mediated by the hippocampus. Immunohistochemical evaluation further revealed a significant reduction in calbindin-positive interneurons in the hippocampus and doublecortin-positive neurons in the dentate gyrus of adult SG(+/-) mice. Heterozygous constitutive deletion of SynGAP is therefore associated with notable behavioural as well as morphological phenotypes indicative of hippocampal dysfunction. Any suggestion of a possible causal link between them however remains a matter for further investigation.

Effects of exercise and enrichment on behaviour in CD-1 mice.

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Aujnarain, Amiirah B; Luo, Owen D; Taylor, Natalie; Lai, Jonathan K Y; Foster, Jane A

2018-04-16

A host of scholarly work has characterized the positive effects of exercise and environmental enrichment on behaviour and cognition in animal studies. The purpose of this study was to investigate the uptake and longitudinal impact of exercise and enrichment on the behavioural phenotype of male and female CD-1 mice. CD-1 mice housed in standard (STD) or exercise and enrichment (EE) conditions post-weaning were tested in the 3-chamber sociability test, open field, and elevated plus maze and exercise activity was monitored throughout the enrichment protocol. Male and female EE mice both showed reduced anxiety and activity in the open field and elevated plus maze relative to sex-matched STD mice. EE altered social behaviours in a sex-specific fashion, with only female EE mice showing increased social preference relative to female STD mice and a preference for social novelty only present in male EE mice. This sexual dimorphism was not observed to be a product of exercise uptake, as CD-1 mice of both sexes demonstrated a consistent trend of wheel rotation frequencies. These findings suggest the importance of considering variables such as sex and strain on experimental design variables in future work on environmental enrichment. Copyright © 2018 Elsevier B.V. All rights reserved.

Acute and chronic dosing of Lepidium meyenii (Maca) on male rat sexual behavior.

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Lentz, Aaron; Gravitt, Karla; Carson, Culley C; Marson, Lesley

2007-03-01

The use of natural remedies for the treatment of sexual disorders is under current investigation. For generations people of the rural community in Peru have used Lepidium meyenii Walpers (Maca), because of their belief that it improves fertility and sexual desire. To determine the acute and chronic effects of Maca on male sexual behavior and to examine chronic administration of Maca on anxiety. Ejaculatory and mounting behavior and postejaculatory interval. Anxiety tests using an elevated plus maze, locomotion, and social interaction with another male. Maca (25 and 100 mg/kg) was orally administered to male rats for 30 days. Male sexual behavior was monitored after acute, 7 and 21 days of treatment. Anxiety behavior and locomotion were measured at 28-29 days using the elevated plus maze and social interaction tests. Maca treatment did not produce large changes in male sexual behavior. However, an increase in ejaculation latency and postejaculatory interval was observed after both acute and 7 days of treatment. After 21 days of treatment Maca had no effect on sexual behavior. Chronic administration of Maca did not increase locomotion or anxiety. Acute and short-term administration of Maca produced a small effect of rat male sexual behavior and long-term administration did not increase anxiety.

Effect of environmental enrichment on physical and psychological dependence signs and voluntary morphine consumption in morphine-dependent and morphine-withdrawn rats.

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Hammami-Abrand Abadi, Arezoo; Miladi-Gorji, Hossein; Bigdeli, Imanollah

2016-04-01

This study was designed to examine the effect of environmental enrichment during morphine dependency and withdrawal on the severity of naloxone-precipitated withdrawal signs, anxiety, and depressive-like behaviors and voluntary morphine consumption in morphine-dependent rats. The rats were injected with bi-daily doses (10 mg/kg, 12 h intervals) of morphine for 14 days following rearing in a standard environment (SE) or enriched environment (EE) during the development of morphine dependence and withdrawal. Then, rats were tested for withdrawal signs after naloxone injection, anxiety (the elevated plus maze) and depression-related behavior (sucrose preference test), and voluntary consumption of morphine using a two-bottle choice paradigm, in morphine-dependent and morphine-withdrawn rats. The results showed that EE decreased naloxone-precipitated withdrawal signs, but not anxiety or sucrose preference during dependence on morphine. The EE-withdrawn rats showed an increase in the elevated plus maze open arm time and entries and higher levels of sucrose preference than SE rats. Voluntary consumption of morphine was lower in the EE-withdrawn rats than in the SE groups in the second period of drug intake. Thus, exposure to EE reduced the severity of morphine dependence and voluntary consumption of morphine, alongside reductions in anxiety and depression-related behavior in morphine-withdrawn rats.

Recovery of behavioral changes and compromised white matter in C57BL/6 mice exposed to cuprizone: Effects of antipsychotic drugs

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Haiyun eXu

2011-07-01

Full Text Available Recent animal and human studies have suggested that the cuprizone (CPZ, a copper chelator-feeding C57BL/6 mouse may be used as an animal model of schizophrenia. The goals of this study were to see the recovery processes of CPZ-induced behavioral changes and damaged white matter and to examine possible effects of antipsychotic drugs on the recovery processes. Mice were fed a CPZ-containing diet for five weeks then returned to normal food for three weeks, during which period mice were treated with different antipsychotic drugs. Various behaviors were measured at the end of CPZ-feeding phase as well as on the 14th and 21st days after CPZ-withdrawal. The damage to and recovery status of white matter in the brains of mice were examined. Dietary CPZ resulted in white matter damage and behavioral abnormalities in the elevated plus-maze, social interaction and Y-maze test. Elevated plus-maze performance recovered to normal range within two weeks after CPZ withdrawal. But, alterations in social interaction showed no recovery. Antipsychotics did not alter animals’ behavior in either of these tests during the recovery period. Altered performance in the Y-maze showed some recovery in the vehicle group; atypical antipsychotics, but not haloperidol, significantly promoted this recovery process. The recovery of damaged white matter was incomplete during the recovery period. None of the drugs significantly promoted the recovery of damaged white matter. These results suggest that CPZ-induced white matter damage and social interaction deficit may be resistant to the antipsychotic treatment employed in this study. They are in good accordance with the clinical observations that positive symptoms in schizophrenic patients respond well to antipsychotic drugs while social dysfunction is usually intractable.

Delayed-matching-to-place Task in a Dry Maze to Measure Spatial Working Memory in Mice.

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Feng, Xi; Krukowski, Karen; Jopson, Timothy; Rosi, Susanna

2017-07-05

The delayed-matching-to-place (DMP) dry maze test is a variant of DMP water maze (Steele and Morris, 1999; Faizi et al. , 2012) which measures spatial working/episodic-like learning and memory that depends on both hippocampal and cortical functions (Wang and Morris, 2010; Euston et al. , 2012). Using this test we can detect normal aging related spatial working memory decline, as well as trauma induced working memory deficits. Furthermore, we recently reported that fractionated whole brain irradiation does not affect working memory in mice (Feng et al. , 2016). Here we describe the experimental setup and procedures of this behavioral test.

Reduction in the anxiolytic effects of ethanol by centrally formed acetaldehyde: the role of catalase inhibitors and acetaldehyde-sequestering agents.

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Correa, M; Manrique, H M; Font, L; Escrig, M A; Aragon, C M G

2008-11-01

Considerable evidence indicates that brain ethanol metabolism mediated by catalase is involved in modulating some of the behavioral and physiological effects of this drug, which suggests that the first metabolite of ethanol, acetaldehyde, may have central actions. Previous results have shown that acetaldehyde administered into the lateral ventricles produced anxiolysis in a novel open arena in rats. The present studies investigate the effects of centrally formed acetaldehyde on ethanol-induced anxiolysis. The effects of the catalase inhibitor sodium azide (SA; 0 or 10 mg/kg, IP) on ethanol-induced anxiolysis (0.0, 0.5, or 1.0 g/kg, IP) were evaluated in CD1 mice in two anxiety paradigms, the elevated plus maze and the dark/light box. Additional studies assessed the effect of the noncompetitive catalase inhibitor 3-amino-1,2,4-triazole (AT; 0.5 g/kg, IP) and the acetaldehyde inactivation agent D: -penicillamine (50 mg/kg, IP) on the plus maze. SA reduced the anxiolytic effects of ethanol on several parameters evaluated in the elevated plus maze and in the dark/light box. In the plus maze, AT completely blocked and D-penicillamine significantly reduced the anxiolytic properties of ethanol. Thus, when cerebral metabolism of ethanol into acetaldehyde is blocked by catalase inhibitors, or acetaldehyde is inactivated, there is a suppressive effect on the anxiolytic actions of ethanol. These data provide further support for the idea that centrally formed or administered acetaldehyde can contribute to some of the psychopharmacological actions of ethanol, including its anxiolytic properties.

Studies into the anxiolytic actions of agomelatine in social isolation reared rats: Role of corticosterone and sex.

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Regenass, Wilmie; Möller, Marisa; Harvey, Brian H

2018-02-01

Anxiety disorders are severely disabling, while current pharmacological treatments are complicated by delayed onset, low remission rates and side-effects. Sex is also noted to contribute towards illness severity and treatment response. Agomelatine is a melatonin (MT 1 /MT 2 ) agonist and serotonin (5-HT 2C ) antagonist purported to be anxiolytic in clinical and some pre-clinical studies. We undertook a detailed analysis of agomelatine's anxiolytic activity in a neurodevelopmental model of anxiety, the social isolation reared rat. Rats received sub-chronic treatment with vehicle or agomelatine (40 mg/kg per day intraperitoneally at 16:00 h for 16 days), with behaviour analysed in the open field test, social interaction test and elevated plus maze. The contribution of corticosterone and sex was also studied. Social isolation rearing increased locomotor activity and reduced social interaction in the social interaction test, and was anxiogenic in the elevated plus maze in males and females. Agomelatine reversed these behaviours. Male and female social isolation reared rats developed anxiety-like behaviours to a similar degree, although response to agomelatine was superior in male rats. Social isolation rearing decreased plasma corticosterone in both sexes and tended to higher levels in females, although agomelatine did not affect corticosterone in either sex. Concluding, agomelatine is anxiolytic in SIR rats, although correcting altered corticosterone could not be implicated. Sex-related differences in the response to agomelatine are evident.

Performance of four different rat strains in the autoshaping, two-object discrimination, and swim maze tests of learning and memory.

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Andrews, J S; Jansen, J H; Linders, S; Princen, A; Broekkamp, C L

1995-04-01

The performance of four strains of rats commonly used in behavioural research was assessed in three different tests of learning and memory. The four strains included three outbred lines (Long-Evans, Sprague-Dawley, Wistar) and one inbred strain (S3). Learning and memory were tested using three different paradigms: autoshaping of a lever press, a two-object discrimination test, and performance in a two-island swim maze task. The pigmented strains showed better performance in the autoshaping procedure: the majority of the Long-Evans and the S3 rats acquired the response, and the majority of the Wistar and Sprague-Dawley failed to acquire the response in the set time. The albino strains were slightly better in the swim maze than the pigmented strains. There appeared to be a speed/accuracy trade-off in the strategy used to solve the task. This was also evident following treatment with the cholinergic-depleting agent hemicholinium-3. The performance of the Long-Evans rats was most affected by the treatment in terms of accuracy and the Wistar and Sprague-Dawleys in terms of speed. In the two-object discrimination test only the Long-Evans showed satisfactory performance and were able to discriminate a novel from a known object a short interval after initial exposure. These results show large task- and strain-dependent differences in performance in tests of learning and memory. Some of the performance variation may be due to emotional differences between the strains and may be alleviated by extra training. However, the response to pharmacological manipulation may require more careful evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

Behavioral deficits in sepsis-surviving rats induced by cecal ligation and perforation

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T. Barichello

2007-06-01

Full Text Available Sepsis and its complications are the leading causes of mortality in intensive care units, accounting for 10-50% of deaths. Intensive care unit survivors present long-term cognitive impairment, including alterations in memory, attention, concentration, and/or global loss of cognitive function. In the present study, we investigated behavioral alterations in sepsis-surviving rats. One hundred and ten male Wistar rats (3-4 months, 250-300 g were submitted to cecal ligation and puncture (CLP, and 44 were submitted to sham operation. Forty-four rats (40% survived after CLP, and all sham-operated animals survived and were used as control. Twenty animals of each group were used in the object recognition task (10 in short-term memory and 10 in long-term memory, 12 in the plus-maze test and 12 in the forced swimming test. Ten days after surgery, the animals were submitted individually to an object recognition task, plus-maze and forced swimming tests. A significant impairment of short- and long-term recognition memory was observed in the sepsis group (recognition index 0.75 vs 0.55 and 0.74 vs 0.51 for short- and long-term memory, respectively (P < 0.05. In the elevated plus-maze test no difference was observed between groups in any of the parameters assessed. In addition, sepsis survivors presented an increase in immobility time in the forced swimming test (180 vs 233 s, P < 0.05, suggesting the presence of depressive-like symptoms in these animals after recovery from sepsis. The present results demonstrated that rats surviving exposure to CLP, a classical sepsis model, presented recognition memory impairment and depressive-like symptoms but not anxiety-like behavior.

Can an aversive, extinction-resistant memory trigger impairments in walking adaptability? An experimental study using adult rats.

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Medeiros, Filipe Mello; de Carvalho Myskiw, Jociane; Baptista, Pedro Porto Alegre; Neves, Laura Tartari; Martins, Lucas Athaydes; Furini, Cristiane Regina Guerino; Izquierdo, Iván; Xavier, Léder Leal; Hollands, Kristen; Mestriner, Régis Gemerasca

2018-02-05

Cognitive demands can influence the adaptation of walking, a crucial skill to maintain body stability and prevent falls. Whilst previous research has shown emotional load tunes goal-directed movements, little attention has been given to this finding. This study sought to assess the effects of suffering an extinction-resistant memory on skilled walking performance in adult rats, as an indicator of walking adaptability. Thus, 36 Wistar rats were divided in a two-part experiment. In the first part (n=16), the aversive, extinction-resistance memory paradigm was established using a fear-conditioning chamber. In the second, rats (n=20) were assessed in a neutral room using the ladder rung walking test before and tree days after inducing an extinction-resistance memory. In addition, the elevated plus-maze test was used to control the influence of the anxiety-like status on gait adaptability. Our results revealed the shock group exhibited worse walking adaptability (lower skilled walking score), when compared to the sham group. Moreover, the immobility time in the ladder rung walking test was similar to the controls, suggesting that gait adaptability performance was not a consequence of the fear generalization. No anxiety-like behavior was observed in the plus maze test. Finally, correlation coefficients also showed the skilled walking performance score was positively correlated with the number of gait cycles and trial time in the ladder rung walking test and the total crossings in the plus maze. Overall, these preliminary findings provide evidence to hypothesize an aversive, extinction-resistant experience might change the emotional load, affecting the ability to adapt walking. Copyright © 2017. Published by Elsevier B.V.

Sensitivity and specificity of the AdenoPlus test for diagnosing adenoviral conjunctivitis.

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Sambursky, Robert; Trattler, William; Tauber, Shachar; Starr, Christopher; Friedberg, Murray; Boland, Thomas; McDonald, Marguerite; DellaVecchia, Michael; Luchs, Jodi

2013-01-01

To compare the clinical sensitivity and specificity of the AdenoPlus test with those of both viral cell culture (CC) with confirmatory immunofluorescence assay (IFA) and polymerase chain reaction (PCR) at detecting the presence of adenovirus in tear fluid. A prospective, sequential, masked, multicenter clinical trial enrolled 128 patients presenting with a clinical diagnosis of acute viral conjunctivitis from a combination of 8 private ophthalmology practices and academic centers. Patients were tested with AdenoPlus, CC-IFA, and PCR to detect the presence of adenovirus. The sensitivity and specificity of AdenoPlus were assessed for identifying cases of adenoviral conjunctivitis. Of the 128 patients enrolled, 36 patients' results were found to be positive by either CC-IFA or PCR and 29 patients' results were found to be positive by both CC-IFA and PCR. When compared only with CC-IFA, AdenoPlus showed a sensitivity of 90% (28/31) and specificity of 96% (93/97). When compared only with PCR, AdenoPlus showed a sensitivity of 85% (29/34) and specificity of 98% (89/91). When compared with both CC-IFA and PCR, AdenoPlus showed a sensitivity of 93% (27/29) and specificity of 98% (88/90). When compared with PCR, CC-IFA showed a sensitivity of 85% (29/34) and specificity of 99% (90/91). AdenoPlus is sensitive and specific at detecting adenoviral conjunctivitis. An accurate and rapid in-office test can prevent the misdiagnosis of adenoviral conjunctivitis that leads to the spread of disease, unnecessary antibiotic use, and increased health care costs. Additionally, AdenoPlus may help a clinician make a more informed treatment decision regarding the use of novel therapeutics. clinicaltrials.gov Identifier: NCT00921895.

Effects of acute caffeine on anxiety-related behavior in rats chronically exposed to the drug, with some evidence of possible withdrawal-reversal.

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Hughes, Robert N; Hancock, Nicola J

2017-03-15

For 20days male and female PVG/c hooded rats were provided with caffeinated (approximately 50mg/kg/day) or unadulterated drinking water, and then their anxiety-related behavior was observed in an open field and elevated plus maze. Their choices of a brightness change were also observed in a Y maze to assess any caffeine effects on spatial memory. 24h later, all rats were tested again following an intraperitoneal injection of 50mg/kg acute caffeine, or vehicle. Earlier chronic caffeine decreased ambulation, walking, rearing, center occupancy and increased immobility in the open field thereby suggesting increased anxiety. However, occupancy of the plus-maze open arms and the Y-maze novel arm were increased by caffeine for male rats, but decreased for females probably because of sex differences in control levels of the response rather than to drug effects on anxiety and memory respectively. Following caffeine withdrawal, acute caffeine had the opposite effect to chronic treatment namely, increased open-field ambulation, walking, center occupancy and decreased immobility and defecation for caffeine-naïve rats that were suggestive of decreased anxiety. Similar but more consistent effects (plus decreased emergence latencies from a darkened start box into the open field) also typified the caffeine-experienced rats which in this case may have been accentuated by caffeine withdrawal-reversal. There was no evidence of either chronic or acute caffeine affecting spatial memory measured in the Y maze. There were also examples of lower overall activity and higher anxiety in male rats, than in females, and some sex-dependent caffeine effects. Copyright © 2016 Elsevier B.V. All rights reserved.

DBI/ACBP loss-of-function does not affect anxiety-like behaviour but reduces anxiolytic responses to diazepam in mice

DEFF Research Database (Denmark)

Budry, Lionel; Bouyakdan, Khalil; Tobin, Stephanie

2016-01-01

. Male and female ACBP(GFAP) KO and ACBP KO mice do not show significant changes in anxiety-like behaviour compared to control littermates during elevated plus maze (EPM) and open field (OF) tests. Surprisingly, ACBP(GFAP) KO and ACBP KO mice were unresponsive to the anxiolytic effect of a low dose...... of diazepam during EPM tests. In conclusion, our experiments using genetic ACBP loss-of-function models suggest that endozepines deficiency does not affect anxiety-like behaviour in mice and impairs the anxiolytic action of diazepam....

Effect of single and fractionated x-irradiation on maze learning ability of mice

International Nuclear Information System (INIS)

Aoyama, Takashi; Norimura, Toshiyuki; Nakamura, Takeshi; Yoshikawa, Isao

1976-01-01

Fifty-six-day-old male ddk mice at the starting of the investigation were used as subjects through the experiment for 64 weeks. After 15 days' preliminary training, and 16 times of weekly trial training using complete maze, 15 mice received a single 224 rads of x-rays (S group), another 15 mice received two 112 rads spaced two weeks apart (F group) and another 15 mice were sham-irradiated (Control group). Then those mice were tested on the multiple T-maze with nine-choice points and change of performance was observed in terms of errorchoices by giving one test trial a week. We introduced the concept of ''confusional trials'' as an index for surmising to what extent mice failed to exhibit good maze learning habits. In the results, the F group showed significantly worse performance than the two other groups at early stages, opposite to it the S group exhibited the same, but at late stages after irradiation. The worse performance of F group should be considered to be due to the psychological after-effect to fractionated irradiation and that for S group could be assumed to be due to the acceleration of aging by the irradiation. (auth.)

Strain-dependent effects of acute caffeine on anxiety-related behavior in PVG/c, Long-Evans and Wistar rats.

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Hughes, Robert N; Hancock, Nicola J

2016-01-01

To assess the possibility that acute caffeine's behavioral action might depend on rats' strain, effects of 50mg/kg of the drug were observed on activity, anxiety-related behavior and habituation learning in male and female rats from three different strains, namely PVG/c, Long-Evans and Wistar. All subjects were tested in an open field, an elevated plus maze and a light-dark box. For the three strains combined, increased occupancy of the center of the open field and entries of the open plus-maze arms with caffeine suggested caffeine-induced anxiolysis, whereas increased grooming in the open field, decreased rearing in the plus maze and increased risk assessment in the light-dark box were consistent with anxiogenesis. Caffeine also reduced open-field rearing only for PVG/c rats, and entries into and occupation of the light side of the light-dark box only for Long-Evans rats, and increased total defecation in the three types of apparatus for all three strains combined. Overall, caffeine appeared to be mainly anxiogenic. The drug also increased open-field ambulation for PVG/c rats and walking for all rats, but decreased open-field ambulation and entries into the plus maze closed arms for Wistar rats alone. In general, Wistar rats appeared to be the least and Long-Evans the most anxious of the three strains investigated. Caffeine also decreased within-session habituation of open-field ambulation for PVG/c rats alone, thereby suggesting strain-dependent interference with non-associative learning and short-term memory. Several overall sex differences were also observed that supported female rats being more active and less anxious than males. Copyright © 2015 Elsevier Inc. All rights reserved.

Neuro-pharmacological potentials of Buchholzia coriacea (Engl.) seeds in laboratory rodents.

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Onasanwo, S A; Obembe, O O; Faborode, S O; Elufioye, T O; Adisa, R A

2013-06-01

Buchholzia coriacea, taken by elderly, has phytochemicals that have neuro-active metabolites, and the folklore documented its use in neuro-behavioural despairs. This study was conducted to investigate the neuro-pharmacological potentials of Buchholzia coriacea (MEBC) seed extract in the laboratory rodents. Methanol extract of the seeds on B. coriacea (MEBC) was evaluated for its antidepressant (Forced Swimming Test and Tail Suspension Test), anxiolytic (Light-Dark Test, Hole Board Test and Elevated Plus Maze), antinociceptive (Hot-Plate and Tail Flick test) and motor coordination (Rota Rod) functions in mice. Our findings showed antidepressant activity (P neuro-physiological disorders like depression, anxiety and pain.

Elevated Fixed Platform Test Facility

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Federal Laboratory Consortium — The Elevated Fixed Platform (EFP) is a helicopter recovery test facility located at Lakehurst, NJ. It consists of a 60 by 85 foot steel and concrete deck built atop...

Induction of habits in rats by a forced-choice procedure in T-maze and the effect of pre-test free exploration

DEFF Research Database (Denmark)

Moustgaard, Anette; Hau, Jann

2009-01-01

the opportunity to explore the entire maze immediately before the free-choice challenge after 200 forced-choice trials, this resulted in a large variation in the choice pattern of the individual rats, and a subgroup of rats choose the newly opened maze arm in 95-100% of the 20 free-choice trials....

Anxiolytic effects of orcinol glucoside and orcinol monohydrate in mice.

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Wang, Xiaohong; Li, Guiyun; Li, Peng; Huang, Linyuan; Huang, Jianmei; Zhai, Haifeng

2015-06-01

Anxiety is a common psychological disorder, often occurring in combination with depression, but therapeutic drugs with high efficacy and safety are lacking. Orcinol glucoside (OG) was recently found to have an antidepressive action. To study the therapeutic potential of OG and orcinol monohydrate (OM) as anxiolytic agents. Anxiolytic effects in mice were measured using the elevated plus-maze, hole-board, and open-field tests. Eight groups of mice were included in each test. Thirty minutes before each test, mice in each group received one oral administration of OG (5, 10, or 20 mg/kg), OM (2.5, 5, or 10 mg/kg), the positive control diazepam (1 or 5 mg/kg), or control vehicle. Each mouse underwent only one test. Uptake of orcinol (5 mg/kg) in the brain was qualitatively detected using the HPLC-MS method. OG (5, 10, and 20 mg/kg) and OM (2.5 and 5 mg/kg) increased the time spent in open arms and the number of entries into open arms in the elevated plus-maze test. OG (5 and 10 mg/kg) and OM (2.5 and 5 mg/kg) increased the number of head-dips in the hole-board test. At all tested doses, OG and OM did not significantly affect the locomotion of mice in the open-field test. Orcinol could be detected in the mouse brain homogenates 30 min after oral OM administration, having confirmed that OM is centrally active. The results demonstrated that OG and OM are anxiolytic agents without sedative effects, indicating their therapeutic potential for anxiety.

Adolescent mice show anxiety- and aggressive-like behavior and the reduction of long-term potentiation in mossy fiber-CA3 synapses after neonatal maternal separation.

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Shin, S Y; Han, S H; Woo, R-S; Jang, S H; Min, S S

2016-03-01

Exposure to maternal separation (MS) during early life is an identified risk factor for emotional disorders such as anxiety and depression later in life. This study investigated the effects of neonatal MS on the behavior and long-term potentiation (LTP) as well as basic synaptic transmission at hippocampal CA3-CA1 and mossy fiber (MF)-CA3 synapses in adolescent mice for 19days. When mice were adolescents, we measured depression, learning, memory, anxious and aggressive behavior using the forced swimming test (FST), Y-maze, Morris water maze (MWM), elevated plus maze (EPM), three consecutive days of the open field test, the social interaction test, the tube-dominance test and the resident-intruder test. The results showed that there was no difference in FST, Y-maze, and MWM performance. However, MS mice showed more anxiety-like behavior in the EPM test and aggressive-like behavior in the tube-dominance and resident-intruder tests. In addition, the magnitude of LTP and release probability in the MF-CA3 synapses was reduced in the MS group but not in the CA3-CA1 synapse. Our results indicate that early life stress due to MS may induce anxiety- and aggressive-like behavior during adolescence, and these effects are associated with synaptic plasticity at the hippocampal MF-CA3 synapses. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Antidepressant-like effects of a water-soluble extract from the culture medium of Ganoderma lucidum mycelia in rats.

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Matsuzaki, Hirokazu; Shimizu, Yuta; Iwata, Naohiro; Kamiuchi, Shinya; Suzuki, Fumiko; Iizuka, Hiroshi; Hibino, Yasuhide; Okazaki, Mari

2013-12-26

Ganoderma lucidum is a popular medicinal mushroom used for promoting health and longevity in Asian countries. Previously, we reported that a water-soluble extract from a culture medium of Ganoderma lucidum mycelia (MAK) exerts antioxidative and cerebroprotective effects against ischemia-reperfusion injury in vivo. Here, we evaluated the antidepressant and anxiolytic activities of MAK in rats. MAK (0.3 or 1 g/kg, p.o.) was administered in the experimental animals 60 min before the forced swimming, open-field, elevated plus-maze, contextual fear-conditioning, and head twitch tests. Additionally, the mechanisms involved in the antidepressant-like action of MAK were investigated by the serotonin precursor 5-hydroxy-L-tryptophan (5-HTP)- or 5-HT2A agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI)-induced head twitch responses. Treatment with MAK (1 g/kg) exhibited antidepressant-like effects in the forced swimming test, attenuated freezing behavior in the contextual fear-conditioning test, and decreased the number of head twitches induced by DOI, but not with 5-HTP. No significant response was observed in locomotion or anxiety-like behavior, when the animals were evaluated in the open-field or elevated plus-maze test, respectively. These data suggest that MAK has antidepressant-like potential, which is most likely due to the antagonism of 5-HT2A receptors, and possesses anxiolytic-like effects toward memory-dependent and/or stress-induced anxiety in rats.

High Resolution UHPLC-MS Metabolomics and Sedative-Anxiolytic Effects of Latua pubiflora: A Mystic Plant used by Mapuche Amerindians.

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Sánchez-Montoya, Eliana L; Reyes, Marco A; Pardo, Joel; Nuñez-Alarcón, Juana; Ortiz, José G; Jorge, Juan C; Bórquez, Jorge; Mocan, Andrei; Simirgiotis, Mario J

2017-01-01

Latua pubiflora (Griseb) Phil. Is a native shrub of the Solanaceae family that grows freely in southern Chile and is employed among Mapuche aboriginals to induce sedative effects and hallucinations in religious or medicine rituals since prehispanic times. In this work, the pentobarbital-induced sleeping test and the elevated plus maze test were employed to test the behavioral effects of extracts of this plant in mice. The psychopharmacological evaluation of L. pubiflora extracts in mice determined that both alkaloid-enriched as well as the non-alkaloid extracts produced an increase of sleeping time and alteration of motor activity in mice at 150 mg/Kg. The alkaloid extract exhibited anxiolytic effects in the elevated plus maze test, which was counteracted by flumazenil. In addition, the alkaloid extract from L. pubiflora decreased [ 3 H]-flunitrazepam binding on rat cortical membranes. In this study we have identified 18 tropane alkaloids (peaks 1-4, 8-13, 15-18, 21, 23, 24, and 28), 8 phenolic acids and related compounds (peaks 5-7, 14, 19, 20, 22, and 29) and 7 flavonoids (peaks 25-27 and 30-33) in extracts of L. pubiflora by UHPLC-PDA-MS which are responsible for the biological activity. This study assessed for the first time the sedative-anxiolytic effects of L. pubiflora in rats besides the high resolution metabolomics analysis including the finding of pharmacologically important tropane alkaloids and glycosylated flavonoids.

Possible Modulation of the Anexiogenic Effects of Vitex Agnus-castus by the Serotonergic System

OpenAIRE

Yaghmaei, Parichehr; Oryan, Shahrbanoo; Fatehi Gharehlar, Laleh; Salari, Ali-Akbar; Solati, Jalal

2012-01-01

Objective(s) There is well documented evidence for the increase in widespread use of complementary and alternative medicine in the treatment of physical and psychiatric symptoms and disorders within the populations. In the present study, we investigated the influence of V itex agnus-castus (vitex) on anxiety-like behaviors of rats. Materials and Methods Elevated plus maze which is one of the methods used for testing anxiety is used in our present study. Rats were orally administrated with vit...

Neuropeptide S overcomes short term memory deficit induced by sleep restriction by increasing prefrontal cortex activity.

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Thomasson, Julien; Canini, Frédéric; Poly-Thomasson, Betty; Trousselard, Marion; Granon, Sylvie; Chauveau, Frédéric

2017-12-01

Sleep restriction (SR) impairs short term memory (STM) that might be related to different processes. Neuropeptide S (NPS), an endogenous neuropeptide that improves short term memory, activates arousal and decreases anxiety is likely to counteract the SR-induced impairment of STM. The objective of the present study was to find common cerebral pathways in sleep restriction and NPS action in order to ultimately antagonize SR effect on memory. The STM was assessed using a spontaneous spatial alternation task in a T-maze. C57-Bl/6J male mice were distributed in 4 groups according to treatment (0.1nmol of NPS or vehicle intracerebroventricular injection) and to 20h-SR. Immediately after behavioural testing, regional c-fos immunohistochemistry was performed and used as a neural activation marker for spatial short term memory (prefrontal cortex, dorsal hippocampus) and emotional reactivity (basolateral amygdala and ventral hippocampus). Anxiety-like behaviour was assessed using elevated-plus maze task. Results showed that SR impaired short term memory performance and decreased neuronal activation in cingular cortex.NPS injection overcame SR-induced STM deficits and increased neuronal activation in infralimbic cortex. SR spared anxiety-like behavior in the elevated-plus maze. Neural activation in basolateral nucleus of amygdala and ventral hippocampus were not changed after SR.In conclusion, the present study shows that NPS overcomes SR-induced STM deficits by increasing prefrontal cortex activation independently of anxiety-like behaviour. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

A comparison of the calculation methods of the maze shielding dose

International Nuclear Information System (INIS)

Li Wenqian; Li Junli; Li Pengyu; Tao Yinghua

2009-01-01

This paper gives a theoretical calculating method for the dose rate of the maze of the low-energy accelerators or high-energy accelerators, based on the NCRP report Nos.49, 51 and 151. The multi-legged maze of the Miyun CT workshop of the NUCTECH Company Limited and the arc maze of the radiation laboratory of the Academy of Military Medical Sciences were calculated using this method. The calculating results were compared with the MCNP simulating results and the measured results. For the commonly estimation of the maze dose rate, as long as the parameters chosen properly, this method can give a conservative result, and save time from simulation. It's hoped that this work could offer a reference for the maze design and the dose estimation method in the aftertime. (authors)

Steroid withdrawal in the mouse results in anxiogenic effects of 3alpha,5beta-THP: a possible model of premenstrual dysphoric disorder.

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Smith, Sheryl S; Ruderman, Yevgeniy; Frye, Cheryl; Homanics, Gregg; Yuan, Maoli

2006-06-01

3alpha-OH-5alpha[beta]-pregnan-20-one (THP) is a positive modulator of the GABAA receptor (GABAR), which underlies its reported anxiolytic effect. However, there are conditions such as premenstrual dysphoric disorder (PMDD) where increases in THP levels can be associated with adverse mood. In order to test for conditions where THP might be anxiogenic, we developed a mouse model of THP withdrawal. Because delta-containing GABAR are highly sensitive to THP modulation, results were compared in wild-type and delta knockout mice. Finasteride, a 5alpha-reductase blocker, was administered for 3 days to female wild-type or delta knockout mice. Then, animals were tested in the elevated plus maze, following acute administration of THP, lorazepam, flumazenil, or 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), and results compared to vehicle-injected controls. CA1 hippocampal GABAR alpha4 subunit levels were assessed by Western blot. After THP withdrawal, THP produced anxiogenic effects, decreasing open arm entries on the elevated plus maze, following a brief shock, in contrast to its expected anxiolytic effects. As we have shown in rats, THP withdrawal also resulted in increased expression of the alpha4 subunit in mouse CA1 hippocampus. As expected for increases in alpha4-containing GABAR, THP withdrawn mice were relatively insensitive to the benzodiazepine (BDZ) lorazepam and had atypical responses to the BDZ antagonist flumazenil when tested on the plus maze. In contrast, they showed a greater anxiolytic response to THIP, which has greater efficacy at alpha4betadelta than other GABAR. Although THP withdrawal in delta knockout mice also increased the alpha4 GABAR subunit, the anxiogenic effects of THP and the anxiolytic effects of THIP were not observed, implicating alpha4betadelta GABAR in these effects. Based on these behavioral and pharmacological findings, we suggest that THP withdrawal in the mouse may serve as a rodent model of PMDD.

Acute restriction impairs memory in the elevated T-maze (ETM) and modifies serotonergic activity in the dorsolateral striatum.

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Cruz-Morales, Sara Eugenia; García-Saldívar, Norma Laura; González-López, María Reyes; Castillo-Roberto, Georgina; Monroy, Juana; Domínguez, Roberto

2008-12-16

Serotonin (5-HT) is involved in behaviors such as sleep, eating, memory, in mental disorders like anxiety and depression and plays an important role in the modulation of stress. On the other hand, exposure to stress influence learning as well as declarative and non-declarative memory. These effects are dependent on the type of stressor, their magnitude, and the type of memory. The striatum has been associated with non-declarative procedural memory, while the information about stress effects on procedural memory and their relation with striatal serotonin is scarce. The objective of this study was to evaluate the effects of stress on the modifications of the striatal serotonergic system. In Experiment 1, the effects of either 60 min of restraint (R) or exposure to the elevated T-maze (ETM) was assessed. Exposure to ETM decreased 5-HT concentration and to R increased 5-HT activity ([metabolite]/[neurotransmitter]). In Experiment 2, we evaluated the effects of restraint on ETM trained immediately, 24 or 48 h after restraint. No effects were detected in acquisition or escape latencies, while retention latencies were lower in all groups compared with the non-restrained group, although significant effects were detected immediately and 24h after restraint. The memory impairment seems to be associated with changes in striatal serotonergic system, given that 5-HT concentration increased, while serotonergic activity decreased. The differences in the activity of 5-HT detected in each experiment could be explained by the effects of different stressors on the serotonergic neurons ability to synthesize the neurotransmitter. Thus, we suggest that exposure to stress impairs procedural memory and that striatal serotonin modulates this effect.

Environmental enrichment delays pup-induced maternal behavior in rats.

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Mann, Phyllis E; Gervais, Kristen J

2011-05-01

Adult, virgin rats do not spontaneously display maternal behavior when exposed to foster pups. However, continuous daily exposure of the female to foster pups for about 5-7 days can induce a set of maternal behaviors similar to those shown by postpartum dams. Induction latencies depend upon a number of factors, including the stress and anxiety levels of the female. The goal of this study was to attempt to mitigate the likely stressfulness of being singly housed during testing by enriching the rat's home cage environment and to determine if the concomitant environmental change would alter the latency to express maternal behavior. In addition, the effect of varying the number of test pups used for testing was examined. Two groups of virgin Sprague-Dawley rats were first tested on the elevated plus maze after 1 week of exposure to either control (standard housing) or enriched conditions. One week later, maternal behavior testing began using one or three pups. Upon completion of maternal behavior testing, plasma corticosterone concentrations were determined following a mild stressor. The data indicate that enrichment tends to increase anxiety-like behaviors in the elevated plus maze. In addition, enrichment delayed the onset of maternal behavior irrespective of the number of test pups. There were no effects of environmental enrichment on plasma corticosterone levels following exposure to a stressor. These results indicate that what is considered a modestly enriched environment delays the expression of pup-oriented responses and does not apparently reduce stress or improve performance on all behavioral tasks. Copyright © 2011 Wiley Periodicals, Inc.

Resveratrol ameliorated the behavioral deficits in a mouse model of post-traumatic stress disorder.

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Zhang, Ze-Shun; Qiu, Zhi-Kun; He, Jia-Li; Liu, Xu; Chen, Ji-Sheng; Wang, Yu-Lu

2017-10-01

Post-traumatic stress disorder (PTSD) has become a major psychiatric and neurological issue. Resveratrol is shown to be effective on depression and anxiety. However, the mechanism of anti-PTSD-like effects of resveratrol remains unknown. The present study aimed to explore the possible molecular and cellular mechanisms underlying the anti-PTSD-like effects of resveratrol. Following a 2-day exposure to inescapable electric foot shocks, animals were administered resveratrol (10, 20, and 40mg/kg, i.g.) during the behavioral tests, which included contextual freezing measurement, elevated plus maze test, staircase test, and open field test. Similar to the positive control drug sertraline (15mg/kg, i.g.), the behavioral deficits of stressed mice were blocked by resveratrol (20 and 40mg/kg, i.g.), which reversed the increased freezing time in contextual freezing measurement and the number of rears in the staircase test and blocked the decrease in time and number of entries in open arms in the elevated plus maze test without affecting the locomotor activity in the open field test. In addition, resveratrol (20 and 40mg/kg, i.g.) antagonized the decrease in the levels of progesterone and allopregnanolone in the prefrontal cortex and hippocampus. Furthermore, long-term resveratrol attenuated the dysfunctions of hypothalamic-pituitary-adrenal axis simultaneously. Collectively, the evidence indicated that the anti-PTSD-like effects of resveratrol were associated with the normalization of biosynthesis of neurosteroids in the brain and prevention of the hypothalamic-pituitary-adrenal axis dysfunction. Copyright © 2017. Published by Elsevier Inc.

Neurons in the Amygdala with Response-Selectivity for Anxiety in Two Ethologically Based Tests

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Wang, Dong V.; Wang, Fang; Liu, Jun; Zhang, Lu; Wang, Zhiru; Lin, Longnian

2011-01-01

The amygdala is a key area in the brain for detecting potential threats or dangers, and further mediating anxiety. However, the neuronal mechanisms of anxiety in the amygdala have not been well characterized. Here we report that in freely-behaving mice, a group of neurons in the basolateral amygdala (BLA) fires tonically under anxiety conditions in both open-field and elevated plus-maze tests. The firing patterns of these neurons displayed a characteristic slow onset and progressively increased firing rates. Specifically, these firing patterns were correlated to a gradual development of anxiety-like behaviors in the open-field test. Moreover, these neurons could be activated by any impoverished environment similar to an open-field; and introduction of both comfortable and uncomfortable stimuli temporarily suppressed the activity of these BLA neurons. Importantly, the excitability of these BLA neurons correlated well with levels of anxiety. These results demonstrate that this type of BLA neuron is likely to represent anxiety and/or emotional values of anxiety elicited by anxiogenic environmental stressors. PMID:21494567

Neurons in the amygdala with response-selectivity for anxiety in two ethologically based tests.

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Dong V Wang

Full Text Available The amygdala is a key area in the brain for detecting potential threats or dangers, and further mediating anxiety. However, the neuronal mechanisms of anxiety in the amygdala have not been well characterized. Here we report that in freely-behaving mice, a group of neurons in the basolateral amygdala (BLA fires tonically under anxiety conditions in both open-field and elevated plus-maze tests. The firing patterns of these neurons displayed a characteristic slow onset and progressively increased firing rates. Specifically, these firing patterns were correlated to a gradual development of anxiety-like behaviors in the open-field test. Moreover, these neurons could be activated by any impoverished environment similar to an open-field; and introduction of both comfortable and uncomfortable stimuli temporarily suppressed the activity of these BLA neurons. Importantly, the excitability of these BLA neurons correlated well with levels of anxiety. These results demonstrate that this type of BLA neuron is likely to represent anxiety and/or emotional values of anxiety elicited by anxiogenic environmental stressors.

Neuropeptide Y Y1 receptor hippocampal overexpression via viral vectors is associated with modest anxiolytic-like and proconvulsant effects in mice

DEFF Research Database (Denmark)

Olesen, Mikkel V; Christiansen, Søren Hofman Oliveira; Gøtzsche, Casper René

2012-01-01

overexpression was found to be associated with modest anxiolytic-like effect in the open field and elevated plus maze tests, but no effect was seen on depression-like behavior using the tail suspension and forced swim tests. However, the rAAV-Y1 vector modestly aggravated kainate-induced seizures. These data...... in the hippocampus of adult mice and tested the animals in anxiety- and depression-like behavior. Hippocampal Y1 receptors have been suggested to mediate seizure-promoting effect, so the effects of rAAV-induced Y1 receptor overexpression were also tested in kainate-induced seizures. Y1 receptor transgene...

Inhibition of hormonal and behavioral effects of stress by tryptophan in rats.

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Gul, Sumera; Saleem, Darakhshan; Haleem, Muhammad A; Haleem, Darakhshan Jabeen

2017-11-03

Stress in known to alter hormonal systems. Pharmacological doses of tryptophan, the essential amino acid precursor of serotonin, increase circulating leptin and decrease ghrelin in normal healthy adults. Because systemically injected leptin inhibits stress-induced behavioral deficits and systemically injected serotonin modulates leptin release from the adipocytes, we used tryptophan as a pharmacological tool to modulate hormonal and behavioral responses in unstressed and stressed rats. Leptin, ghrelin, serotonin, tryptophan, and behavior were studied in unstressed and stressed rats following oral administration of 0, 100, 200, and 300 mg/kg of tryptophan. Following oral administration of tryptophan at a dose of 300 mg/kg, circulating levels of serotonin and leptin increased and those of ghrelin decreased in unstressed animals. No effect occurred on 24-hours cumulative food intake and elevated plus maze performance. Exposure to 2 hours immobilization stress decreased 24 hours cumulative food intake and impaired performance in elevated plus maze monitored next day. Serum serotonin decreased, leptin increased, and no effect occurred on ghrelin. Stress effects on serotonin, leptin, food intake, and elevated plus maze performance did not occur in tryptophan-pretreated animals. Tryptophan-induced decreases of ghrelin also did not occur in stressed animals. The findings show an important role of serum serotonin, leptin, and ghrelin in responses to stress and suggest that the essential amino acid tryptophan can improve therapeutics in stress-induced hormonal and behavioral disorders.

Coagulopathy triggered autoimmunity: experimental antiphospholipid syndrome in factor V Leiden mice

Science.gov (United States)

2013-01-01

Background We investigated interactions between genetically and autoimmune-mediated coagulopathies by inducing experimental antiphospholipid syndrome (eAPS) in mice carrying the factor V Leiden (FVL) mutation. Methods eAPS was induced in heterozygous and homozygous FVL transgenic mice (C57BL/6 background) by immunization with β2-glycoprotein I (β2-GPI). Autoantibody levels were measured at 1 and 5 months post-immunization. Mice were tested at 4 months post-immunization for behavior and cognitive function in the staircase, elevated plus-maze, and swim T-maze tests. Brains were removed and analyzed by immunohistochemistry for inflammatory markers and neurodegenerative processes. Results A single immunization with β2-GPI induced significantly higher and longer-lasting immune responses, and this was dependent on the number of FVL alleles. At 1 and 5 months post-immunization, levels of antibodies rose from 1.17 ± 0.07 to 1.62 ± 0.17 (optical density units; ODU) in homozygous FVL mice, compared with stable levels of 0.59 ± 0.17 and 0.48 ± 0.16 ODU in heterozygous FVL mice and a drop from 1.62 ± 0.21 to 0.61 ± 0.13 ODU in wild-type mice. Behavioral and cognitive clinical features of eAPS were also correlated with FVL allele load, as assessed by the elevated plus-maze (altered anxiety), staircase (hyperactivity and higher exploration), and swim T-maze (impaired learning) tests. Histological studies identified significant neurodegenerative changes in both grey and white matter in the eAPS-FVL brains. In spite of the potential interaction of two prothrombotic disease states, there were no ischemic lesions seen in this group. Conclusions The results indicate that genetically mediated coagulopathies increase the risk of developing coagulation-targeted autoimmune responses, and suggest the importance of antibody-mediated neurodegenerative processes in the brain in APS. PMID:23566870

Down-Regulation of Homer1b/c Protects Against Chemically Induced Seizures Through Inhibition of mTOR Signaling

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Lei Cao

2015-03-01

Full Text Available Background: Homer is a family of post synaptic density proteins functionally and physically attached to target proteins at proline-rich sequences. Reducing Homer1b/c expression has been shown in previous studies to be protective against excitotoxic insults, implicating Homer1b/c in the physiological regulation of aberrant neuronal excitability. Methods: To test the efficacy of a Homer1b/c reducing therapy for disorders with a detrimental hyperexcitability profile in mice, we used small interfere RNA (siRNA to decrease endogenous Homer1b/c expression in mouse hippocampus. The baseline motor and cognitive behavior was measured by sensorimotor tests, Morris water maze and elevated plus maze tasks. The anti-epileptic effects of Homer1b/c knockdown were determined in two chemically induced seizure models induced by Picrotoxin (PTX or pentylenetetrazole (PTZ administration. Results: The results of sensorimotor tests, Morris water maze and elevated plus maze tasks showed that Homer1b/c reduction had no effect on baseline motor or cognitive behavior. In two chemically induced seizure models, mice with reduced Homerb/c protein had less severe seizures than control mice. Total Homer1b/c protein levels and seizure severity were highly correlated, such that those mice with the most severe seizures also had the highest levels of Homer1b/c. In addition, the phosphorylation of mammalian target of rapamycin (mTOR and its target protein S6 was significantly inhibited in Homer1b/c down-regulated mice. Homer1b/c knockdown-induced inhibition of mTOR pathway was partially ablated by the metabotropic glutamate receptor 5 (mGluR5 agonist CHPG. Conclusion: Our results demonstrate that endogenous Homer1b/c is integral for regulating neuronal hyperexcitability in adult animals and suggest that reduction of Homer1b/c could protect against chemically induced seizures through inhibition mTOR pathway.

Effect of methanolic extract of Asparagus racemosus Willd. on lipopolysaccharide induced-oxidative stress in rats.

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Ahmad, Mohammad Parwez; Hussain, Arshad; Siddiqui, Hefazat Hussain; Wahab, Shadma; Adak, Manoranjan

2015-03-01

Lipopolysaccharide (LPS) induced oxidative stress and impairment of normal physiological function generally categorized by increased anxiety and reduced mobility. Therefore, the present study was to find out the effect Methanolic extract of Asparagus racemosus (MEAR ) in lipopolysaccharide (LPS)-induced oxidative stress in rats . LPS-induced oxidative stress in rats was measured by locomotor activity by photoactometer test, anxiety with elevated plus maze test and also studied the oxidative stress markers, nitric oxide and cytokines. The obtained data shows that LPS markedly exhausted (pAsparagus racemosus Willd. is a functionally newer type of cerebroprotective agent.

APP transgenic mice for modelling behavioral and psychological symptoms of dementia (BPSD)

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Lalonde, R.; Fukuchi, K.; Strazielle, C.

2012-01-01

The discovery of gene mutations responsible for autosomal dominant Alzheimer's disease has enabled researchers to reproduce in transgenic mice several hallmarks of this disorder, notably Aβ accumulation, though in most cases without neurofibrillary tangles. Mice expressing mutated and wild-type APP as well as C-terminal fragments of APP exhibit variations in exploratory activity reminiscent of behavioral and psychological symptoms of Alzeimer dementia (BPSD). In particular, open-field, spontaneous alternation, and elevated plus-maze tasks as well as aggression are modified in several APP transgenic mice relative to non-transgenic controls. However, depending on the precise murine models, changes in open-field and elevated plus-maze exploration occur in either direction, either increased or decreased relative to controls. It remains to be determined which neurotransmitter changes are responsible for this variability, in particular with respect to GABA, 5HT, and dopamine. PMID:22373961

2-Methyl-6-(phenylethynyl pyridine (MPEP reverses maze learning and PSD-95 deficits in Fmr1 knock-out mice.

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Réno Michelle Gandhi

2014-03-01

Full Text Available Fragile X syndrome (FXS is caused by the lack of expression of the fragile X mental retardation protein (FMRP, which results in intellectual disability and other debilitating symptoms including impairment of visual-spatial functioning. FXS is the only single-gene disorder that is highly co-morbid with autism spectrum disorder and can therefore provide insight into its pathophysiology. Lack of FMRP results in altered group I metabotropic glutamate receptor (mGluR signalling, which is a target for putative treatments. The Hebb-Williams (H-W mazes are a set of increasingly complex spatial navigation problems that depend on intact hippocampal and thus mGluR-5 functioning. In the present investigation, we examined whether an antagonist of mGluR-5 would reverse previously described behavioural deficits in Fmr1 KO mice. Mice were trained on a subset of the H-W mazes and then treated with either 20 mg/kg of an mGluR-5 antagonist, 2-Methyl-6-(phenylethynyl pyridine (MPEP; n = 11 or an equivalent dose of saline (n = 11 prior to running test mazes. Latency and errors were dependent variables recorded during the test phase. Immediately after completing each test, marble-burying behavior was assessed which confirmed that the drug treatment was pharmacologically active during maze learning. Although latency was not statistically different between the groups, MPEP treated Fmr1 KO mice made significantly fewer errors on mazes deemed more difficult suggesting a reversal of the behavioural deficit. MPEP treated mice were also less perseverative and impulsive when navigating mazes. Furthermore, MPEP treatment reversed PSD-95 protein deficits in Fmr1 KO treated mice, whereas levels of a control protein (β-tubulin remained unchanged. These data further validate MPEP as a potentially beneficial treatment for FXS. Our findings also suggest that adapted H-W mazes may be a useful tool to document alterations in behavioural functioning following pharmacological

Blast-Induced Tinnitus and Elevated Central Auditory and Limbic Activity in Rats: A Manganese-Enhanced MRI and Behavioral Study.

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Ouyang, Jessica; Pace, Edward; Lepczyk, Laura; Kaufman, Michael; Zhang, Jessica; Perrine, Shane A; Zhang, Jinsheng

2017-07-07

Blast-induced tinitus is the number one service-connected disability that currently affects military personnel and veterans. To elucidate its underlying mechanisms, we subjected 13 Sprague Dawley adult rats to unilateral 14 psi blast exposure to induce tinnitus and measured auditory and limbic brain activity using manganese-enhanced MRI (MEMRI). Tinnitus was evaluated with a gap detection acoustic startle reflex paradigm, while hearing status was assessed with prepulse inhibition (PPI) and auditory brainstem responses (ABRs). Both anxiety and cognitive functioning were assessed using elevated plus maze and Morris water maze, respectively. Five weeks after blast exposure, 8 of the 13 blasted rats exhibited chronic tinnitus. While acoustic PPI remained intact and ABR thresholds recovered, the ABR wave P1-N1 amplitude reduction persisted in all blast-exposed rats. No differences in spatial cognition were observed, but blasted rats as a whole exhibited increased anxiety. MEMRI data revealed a bilateral increase in activity along the auditory pathway and in certain limbic regions of rats with tinnitus compared to age-matched controls. Taken together, our data suggest that while blast-induced tinnitus may play a role in auditory and limbic hyperactivity, the non-auditory effects of blast and potential traumatic brain injury may also exert an effect.

Acute toxicity of 3,4-methylenedioxymethamphetamine in the anxious mood of rats

Institute of Scientific and Technical Information of China (English)

Suxia Li; Jing Li; Xue Wang; Weihong Kuang; Zugui Peng; Mingsheng Huang

2006-01-01

BACKGROUND: The long-term neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA) mainly caused by repeated exposure to MDMA or a single big dose of MDMA, which results in degeneration of serotonin terminal of central nervous system, and someone believe that the great release of serotonin transmitter in central nervous system will lead to anxious mood.OBJECTIVE: To observe the changes of anxiety related behaviors in rats after single administration of different doses of MDMA.DESIGN: A randomized control study.SETTING: Laboratory of Psychopharmacology of the Mental Health Center, West China Hospital of Sichuan University.MATERIALS: Thirty male adult Wistar rats, weighing (251.3±18.34) g, were used. MDMA were obtained from the National Institute for the Control of Pharmaceutical and Biological Products, and dissolved in saline. All the doses of the drug were administered in a volume of 1 mg/kg.METHODS: The experiment was carried out in the Laboratory of Psychopharmacology of the Mental Health Center, West China Hospital of Sichuan University in July 2003. ①The rats were randomly divided into control group (n=6) and experimental group (n=24), and then those in the latter were randomly assigned into four subgroups of MDMA 3, 5, 10 and 20 mg/kg groups, with 6 rats in each, which were administrated by single intraperitoneal injection of MDMA 3, 5, 10 and 20 mg/kg respectively, and those in the control group were administrated by single intraperitoneal injection of saline of the same volume. ② The open field test,elevated plus-maze test and social interaction test were performed immediately after administration. For the open field test, the apparatus was situated in a darkened room, illuminated by a single 60 W white light bulb located approximately 60 cm above the center of the open field. Before administration, all the rats were placed into the open field to be familiar with the open field for 5 minutes. They were observed for 45 minutes after administration. The

Neonatal administration of fluoxetine did not alter the anxiety indicators, but decreased the locomotor activity in adult rats in the elevated plus-maze Administração neonatal de fluoxetina não alterou os indicadores de ansiedade, mas diminuiu a atividade locomotora em ratos adultos no labirinto elevado em cruz

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Valdenilson Ribeiro Ribas

2008-12-01

Full Text Available The objective of this study was evaluate the anxiety and locomotor activity (LA in 52 Wistar adult male rats, being 26 treated with fluoxetine (10 mg/Kg - sc in the neonatal period. These same rats received foot shock (FS (1.6-mA - 2-s in the 90th day. The anxiety and LA were appraised by plus-maze. The time spent in the open arms was used as anxiety index and the LA was measured by number of entries in closed arms (NECA and the total of entries (TE. T-test was used with pO objetivo deste estudo foi avaliar a ansiedade e a atividade locomotora (AL em 52 ratos Wistar adultos machos, sendo 26 tratados no período neonatal com fluoxetina (10 mg/Kg - sc e no 90º dia, receberam estímulos elétricos nas patas (1,6-mA-2-s. A ansiedade e a AL foram avaliadas por meio do labirinto elevado em cruz. O tempo de permanência dos animais nos braços abertos (BA foi utilizado como índice de ansiedade e a AL medida pelo número de entradas nos braços fechados (NEBF e pelo total de entradas (TE nos BA e BF. O teste t foi utilizado, com (p<0,05 e os dados apresentados em média±erro padrão. Os animais tratados reduziram o NEBF (2,35±0,33 e o TE (3,96±0,61 comparados a seus controles (4,65±0,52 e (6,96±0,94. A administração neonatal de fluoxetina não alterou a ansiedade, mas diminuiu a AL dos animais que receberam EE.

Isolated core vs. superficial cooling effects on virtual maze navigation.

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Payne, Jennifer; Cheung, Stephen S

2007-07-01

Cold impairs cognitive performance and is a common occurrence in many survival situations. Altered behavior patterns due to impaired navigation abilities in cold environments are potential problems in lost-person situations. We investigated the separate effects of low core temperature and superficial cooling on a spatially demanding virtual navigation task. There were 12 healthy men who were passively cooled via 15 degrees C water immersion to a core temperature of 36.0 degrees C, then transferred to a warm (40 degrees C) water bath to eliminate superficial shivering while completing a series of 20 virtual computer mazes. In a control condition, subjects rested in a thermoneutral (approximately 35 degrees C) bath for a time-matched period before being transferred to a warm bath for testing. Superficial cooling and distraction were achieved by whole-body immersion in 35 degree water for a time-matched period, followed by lower leg immersion in 10 degree C water for the duration of the navigational tests. Mean completion time and mean error scores for the mazes were not significantly different (p > 0.05) across the core cooling (16.59 +/- 11.54 s, 0.91 +/- 1.86 errors), control (15.40 +/- 8.85 s, 0.82 +/- 1.76 errors), and superficial cooling (15.19 +/- 7.80 s, 0.77 +/- 1.40 errors) conditions. Separately reducing core temperature or increasing cold sensation in the lower extremities did not influence performance on virtual computer mazes, suggesting that navigation is more resistive to cooling than other, simpler cognitive tasks. Further research is warranted to explore navigational ability at progressively lower core and skin temperatures, and in different populations.

Genistein improves spatial learning and memory in male rats with elevated glucose level during memory consolidation

OpenAIRE

Kohara, Yumi; Kawaguchi, Shinichiro; Kuwahara, Rika; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

2015-01-01

Cognitive dysfunction due to higher blood glucose level has been reported previously. Genistein (GEN) is a phytoestrogen that we hypothesized might lead to improved memory, despite elevated blood glucose levels at the time of memory consolidation. To investigate this hypothesis, we compared the effects of orally administered GEN on the central nervous system in normal versus glucose-loaded adult male rats. A battery of behavioral assessments was carried out. In the MAZE test, which measured s...

Are Sema5a mutant mice a good model of autism? A behavioral analysis of sensory systems, emotionality and cognition

Science.gov (United States)

Gunn, Rhian K.; Huentelman, Matthew J.; Brown, Richard E.

2011-01-01

Semaphorin 5A (Sema5A) expression is reduced in the brain of individuals with autism, thus mice with reduced Sema5A levels may serve as a model of this neurodevelopmental disorder. We tested male and female Sema5a knockout mice (B6.129P2SEMA5A/J) and C57BL/6J controls for emotionality, visual ability, prepulse inhibition, motor learning and cognition. Overall, there were only two genotype differences in emotionality: Sema5a mutant mice had more stretch-attend postures in the elevated plus-maze and more defecations in the open field. All mice could see, but Sema5a mice had better visual ability than C57BL/6J mice. There were no genotype differences in sensory-motor gating. Sema5a mice showed higher levels of activity in the elevated plus-maze and light/dark transition box, and there were sex by genotype differences in the Rotarod, suggesting a sex difference in balance and coordination differentially affected by Sema5a. There were no genotype effects on cognition: Sema5a mice did not differ from C57BL/6J in the Morris water maze, set-shifting or cued and contextual fear conditioning. In the social recognition test, all mice preferred social stimuli, but there was no preference for social novelty, thus the Sema5A mice do not have a deficit in social behavior. Overall, there were a number of sex differences, with females showing greater activity and males performing better in tests of spatial learning and memory, but no deficits in the behavior of Sema5A mice. We conclude that the Sema5a mice do not meet the behavioral criteria for a mouse model of autism. PMID:21777623

Forebrain-Specific Loss of BMPRII in Mice Reduces Anxiety and Increases Object Exploration.

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McBrayer, Zofeyah L; Dimova, Jiva; Pisansky, Marc T; Sun, Mu; Beppu, Hideyuki; Gewirtz, Jonathan C; O'Connor, Michael B

2015-01-01

To investigate the role of Bone Morphogenic Protein Receptor Type II (BMPRII) in learning, memory, and exploratory behavior in mice, a tissue-specific knockout of BMPRII in the post-natal hippocampus and forebrain was generated. We found that BMPRII mutant mice had normal spatial learning and memory in the Morris water maze, but showed significantly reduced swimming speeds with increased floating behavior. Further analysis using the Porsolt Swim Test to investigate behavioral despair did not reveal any differences in immobility between mutants and controls. In the Elevated Plus Maze, BMPRII mutants and Smad4 mutants showed reduced anxiety, while in exploratory tests, BMPRII mutants showed more interest in object exploration. These results suggest that loss of BMPRII in the mouse hippocampus and forebrain does not disrupt spatial learning and memory encoding, but instead impacts exploratory and anxiety-related behaviors.

Forebrain-Specific Loss of BMPRII in Mice Reduces Anxiety and Increases Object Exploration.

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Zofeyah L McBrayer

Full Text Available To investigate the role of Bone Morphogenic Protein Receptor Type II (BMPRII in learning, memory, and exploratory behavior in mice, a tissue-specific knockout of BMPRII in the post-natal hippocampus and forebrain was generated. We found that BMPRII mutant mice had normal spatial learning and memory in the Morris water maze, but showed significantly reduced swimming speeds with increased floating behavior. Further analysis using the Porsolt Swim Test to investigate behavioral despair did not reveal any differences in immobility between mutants and controls. In the Elevated Plus Maze, BMPRII mutants and Smad4 mutants showed reduced anxiety, while in exploratory tests, BMPRII mutants showed more interest in object exploration. These results suggest that loss of BMPRII in the mouse hippocampus and forebrain does not disrupt spatial learning and memory encoding, but instead impacts exploratory and anxiety-related behaviors.

Little and often? Maintaining continued performance in an automated T-maze for mice.

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Gaskill, Brianna N; Lucas, Jeffrey R; Pajor, Edmond A; Garner, Joseph P

2011-02-01

Operant and maze tasks in mice are limited by the small number of trials possible in a session before mice lose motivation. We hypothesized that by manipulating reward size and session length, motivation, and hence performance, would be maintained in an automated T-maze. We predicted that larger rewards and shorter sessions would improve acquisition; and smaller rewards and shorter sessions would maintain higher and less variable performance. Eighteen C57BL/6J mice (9 per sex) acquired (criterion 8/10 correct) and performed a spatial discrimination, with one of 3 reward sizes (.02, .04, or .08 g) and one of 3 session schedules (15, 30, or 45 min sessions). Each mouse had a total of 360 min of access to the maze per night, for two nights, and averaged 190 trials. Analysis used split-plot GLM with contrasts testing for linear effects. Acquisition of the discrimination was unaffected by reward size or session length/interval. After-criterion average performance improved as reward size decreased. After-criterion variability in performance was also affected. Variability increased as reward size increased. Session length/interval did not affect any outcome. We conclude that an automated maze, with suitable reward sizes, can sustain performance with low variability, at 5-10 times faster than traditional methods. Copyright © 2011 Elsevier B.V. All rights reserved.

Neurobehavioral performances and brain regional metabolism in Dab1(scm) (scrambler) mutant mice.

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Jacquelin, C; Lalonde, R; Jantzen-Ossola, C; Strazielle, C

2013-09-01

As disabled-1 (DAB1) protein acts downstream in the reelin signaling pathway modulating neuronal migration, glutamate neurotransmission, and cytoskeletal function, the disabled-1 gene mutation (scrambler or Dab1(scm) mutation) results in ataxic mice displaying dramatic neuroanatomical defects similar to those observed in the reeler gene (Reln) mutation. By comparison to non-ataxic controls, Dab1(scm) mutants showed severe motor coordination impairments on stationary beam, coat-hanger, and rotorod tests but were more active in the open-field. Dab1(scm) mutants were also less anxious in the elevated plus-maze but with higher latencies in the emergence test. In mutants versus controls, changes in regional brain metabolism as measured by cytochrome oxidase (COX) activity occurred mainly in structures intimately connected with the cerebellum, in basal ganglia, in limbic regions, particularly hippocampus, as well as in visual and parietal sensory cortices. Although behavioral results characterized a major cerebellar disorder in the Dab1(scm) mutants, motor activity impairments in the open-field were associated with COX activity changes in efferent basal ganglia structures such as the substantia nigra, pars reticulata. Metabolic changes in this structure were also associated with the anxiety changes observed in the elevated plus-maze and emergence test. These results indicate a crucial participation of the basal ganglia in the functional phenotype of ataxic Dab1(scm) mutants. Copyright © 2013 Elsevier B.V. All rights reserved.

Behavioral effects of Citrus limon and Punica granatum combinations in rats.

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Riaz, Azra; Khan, Rafeeq Alam

2017-02-01

Dietary supplements are becoming more influential as viable treatment for common chronic diseases and to promote normal development and functions of all system including brain. Disorders like anxiety and depression may be managed through healthier variations is dietary pattern, since there are indications that diet rich in antioxidants and vitamins diminish anxiety and depression. Hence this investigation was planned to assess the behavioral effects of Citrus limon and Punica granatum in two combination doses i.e. 0.4 + 5 ml/kg and 0.2 + 8 ml/kg C. limon and P. granatum respectively in rats. Antidepressant and anxiolytic effects were explicitly judged twice during 15 days using forced swimming and open field tests and elevated plus maze. In open field test C. limon and P. granatum showed increase in distance travelled, number of central entries and number of rearing's at 0.4 + 5 ml/kg combination, in the elevated plus maze, number of open arm entries were found to be augmented and in forced swimming test, there was decline in duration of immobility and rise in duration of climbing at both combinations i.e. 0.4 + 5 ml/kg and 0.2 + 8 ml/kg C. limon and P. granatum. These results suggest that C. limon and P. granatum at 0.4 + 5 ml/kg combination have anxiolytic and antidepressant effect.

Genistein improves spatial learning and memory in male rats with elevated glucose level during memory consolidation.

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Kohara, Yumi; Kawaguchi, Shinichiro; Kuwahara, Rika; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

2015-03-01

Cognitive dysfunction due to higher blood glucose level has been reported previously. Genistein (GEN) is a phytoestrogen that we hypothesized might lead to improved memory, despite elevated blood glucose levels at the time of memory consolidation. To investigate this hypothesis, we compared the effects of orally administered GEN on the central nervous system in normal versus glucose-loaded adult male rats. A battery of behavioral assessments was carried out. In the MAZE test, which measured spatial learning and memory, the time of normal rats was shortened by GEN treatment compared to the vehicle group, but only in the early stages of testing. In the glucose-loaded group, GEN treatment improved performance as mazes were advanced. In the open-field test, GEN treatment delayed habituation to the new environment in normal rats, and increased the exploratory behaviors of glucose-loaded rats. There were no significant differences observed for emotionality or fear-motivated learning and memory. Together, these results indicate that GEN treatment improved spatial learning and memory only in the early stages of testing in the normal state, but improved spatial learning and memory when glucose levels increased during memory consolidation. Copyright © 2014 Elsevier Inc. All rights reserved.

Negative transfer effects between reference memory and working memory training in the water maze in C57BL/6 mice.

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Serrano Sponton, Lucas Ezequiel; Soria, Gonzalo Jose; Dubroqua, Sylvain; Singer, Philipp; Feldon, Joram; Gargiulo, Pascual A; Yee, Benjamin K

2018-02-26

The water maze is one of the most widely employed spatial learning paradigms in the cognitive profiling of genetically modified mice. Oftentimes, tests of reference memory (RM) and working memory (WM) in the water maze are sequentially evaluated in the same animals. However, critical difference in the rules governing efficient escape from the water between WM and RM tests is expected to promote the adoption of incompatible mnemonic or navigational strategies. Hence, performance in a given test is likely poorer if it follows the other test instead of being conducted first. Yet, the presence of such negative transfer effects (or proactive interference) between WM and RM training in the water maze is often overlooked in the literature. To gauge whether this constitutes a serious concern, the present study determined empirically the magnitude, persistence, and directionality of the transfer effect in wild-type C57BL/6 mice. We contrasted the order of tests between two cohorts of mice. Performance between the two cohorts in the WM and RM tests were then separately compared. We showed that prior training of either test significantly reduced performance in the subsequent one. The statistical effect sizes in both directions were moderate to large. Although extended training could overcome the deficit, it could re-emerge later albeit in a more transient fashion. Whenever RM and WM water maze tests are conducted sequentially in the same animals - regardless of the test order, extra caution is necessary when interpreting the outcomes in the second test. Counterbalancing test orders between animals is recommended. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuropharmacological evaluation of Annona senegalensis leaves ...

African Journals Online (AJOL)

The neuropharmacological activities of methanol leaf extract (ME) of Annona senegalensis Pers (Annonaceae) and its bioactive fractions (MF and F7) were studied in rodents using pentylenetetrazol (PTZ)-induced seizures, pentobarbitone-induced sleep, apomorphine-induced stereotypy, open field, elevated plus maze ...

Genistein alleviates anxiety-like behaviors in post-traumatic stress disorder model through enhancing serotonergic transmission in the amygdala.

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Wu, Zhong-Min; Ni, Gui-Lian; Shao, Ai-Min; Cui, Rong

2017-09-01

Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder, characterized by intense fear, and increased arousal and avoidance of traumatic events. The current available treatments for PTSD have limited therapeutic value. Genistein, a natural isoflavone, modulates a variety of cell functions. In this study, we tested anti-anxiety activity and underlying mechanisms of genistein in a PTSD rat model. The rats were trained to associate a tone with foot shock delivery on day 0, then fear conditioning was performed on day 7, 14 and 21. Genistein (2-8mg/kg) was injected intraperitoneally daily for 7 days. The anti-anxiety effects of genistein were measured by contextual freezing behavior and elevated plus maze. By the end of the experiments, the amygdala was extracted and subject to neurochemistry analysis. Genistein alleviated contextual freezing behavior and improved performance in elevated plus maze dose-dependently in PTSD rats. Furthermore, in these rats, genistein enhanced serotonergic transmission in the amygdala, including upregulation of tryptophan hydroxylase, serotonin, and phosphorylated (p)-CaMKII and p-CREB, as well. Genistein exerts anti-anxiety effects on a PTSD model probably through enhancing serotonergic system and CaMKII/CREB signaling pathway in the amygdala. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Dairy cow feeding space requirements assessed in a Y-maze choice test.

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Rioja-Lang, F C; Roberts, D J; Healy, S D; Lawrence, A B; Haskell, M J

2012-07-01

The effect of proximity to a dominant cow on a low-ranking cow's willingness to feed was assessed using choice tests. The main aim of the experiment was to determine the feeding space allowance at which the majority of subordinate cows would choose to feed on high-palatability food (HPF) next to a dominant cow rather than feeding alone on low-palatability food (LPF). Thirty Holstein-Friesian cows were used in the study. Half of the cows were trained to make an association between a black bin and HPF and a white bin and LPF, and the other half were trained with the opposite combination. Observations of pair-wise aggressive interactions were observed during feeding to determine the relative social status of each cow. From this, dominant and subordinate cows were allocated to experimental pairs. When cows had achieved an HPF preference with an 80% success rate in training, they were presented with choices using a Y-maze test apparatus, in which cows were offered choices between feeding on HPF with a dominant cow and feeding on LPF alone. Four different space allowances were tested at the HPF feeder: 0.3, 0.45, 0.6, and 0.75 m. At the 2 smaller space allowances, cows preferred to feed alone (choices between feeding alone or not for 0.3- and 0.45-m tests were significantly different). For the 2 larger space allowances, cows had no significant preferences (number of choices for feeding alone or with a dominant). Given that low-status cows are willing to sacrifice food quality to avoid close contact with a dominant animal, we suggest that the feeding space allowance should be at least 0.6m per cow whenever possible. However, even when space allowances are large, it is clear that some subordinate cows will still prefer to avoid proximity to dominant individuals. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Resistance to early-life stress in mice: effects of genetic background and stress duration

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Helene M. Savignac

2011-04-01

Full Text Available Early-life stress can induce marked behavioural and physiological impairments in adulthood including cognitive deficits, depression, anxiety and gastrointestinal dysfunction. Although robust rat models of early-life stress exist there are few established effective paradigms in the mouse. Genetic background and protocol parameters used are two critical variables in such model development.Thus we investigated the impact of two different early-life stress protocols in two commonly used inbred mouse strains. C57BL/6 and innately anxious BALB/c male mice were maternally deprived 3 hrs daily, either from postnatal day 1 to 14 (Protocol 1 or 6 to 10 (Protocol 2. Animals were assessed in adulthood for cognitive performance (spontaneous alternation behaviour test, anxiety (open field, light/dark box and elevated plus maze tests and depression-related behaviours (forced swim test in addition to stress-sensitive physiological changes. Overall, the results showed that early-life stressed mice from both strains displayed good cognitive ability and no elevations in anxiety. However, paradoxical changes occurred in C57BL/6 mice as the longer protocol (protocol 1 decreased anxiety in the light-dark box and increased exploration in the elevated plus maze. In BALB/c mice there were also limited effects of maternal separation with both separation protocols inducing reductions in stress-induced defecation and protocol 1 reducing the colon length. These data suggest that, independent of stress duration, mice from both strains were on the whole resilient to the maladaptive effects of early-life stress. Thus maternal-separation models of brain-gut axis dysfunction should rely on either different stressor protocols or other strains of mice.

Acute stress switches spatial navigation strategy from egocentric to allocentric in a virtual Morris water maze.

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van Gerven, Dustin J H; Ferguson, Thomas; Skelton, Ronald W

2016-07-01

Stress and stress hormones are known to influence the function of the hippocampus, a brain structure critical for cognitive-map-based, allocentric spatial navigation. The caudate nucleus, a brain structure critical for stimulus-response-based, egocentric navigation, is not as sensitive to stress. Evidence for this comes from rodent studies, which show that acute stress or stress hormones impair allocentric, but not egocentric navigation. However, there have been few studies investigating the effect of acute stress on human spatial navigation, and the results of these have been equivocal. To date, no study has investigated whether acute stress can shift human navigational strategy selection between allocentric and egocentric navigation. The present study investigated this question by exposing participants to an acute psychological stressor (the Paced Auditory Serial Addition Task, PASAT), before testing navigational strategy selection in the Dual-Strategy Maze, a modified virtual Morris water maze. In the Dual-Strategy maze, participants can chose to navigate using a constellation of extra-maze cues (allocentrically) or using a single cue proximal to the goal platform (egocentrically). Surprisingly, PASAT stress biased participants to solve the maze allocentrically significantly more, rather than less, often. These findings have implications for understanding the effects of acute stress on cognitive function in general, and the function of the hippocampus in particular. Copyright © 2016 Elsevier Inc. All rights reserved.

Amazeobot : The construction of a maze mapping robot

OpenAIRE

REBECCA, WIKSTRÖM; MARTIN, SJÖGREN

2016-01-01

For the purpose of exploring how a computer can navigate through a maze, this project examines how a robot’s surroundings can be interpreted, mapped and navigated through, by applying common maze solving algorithms. The execution of the project involves infrared sensors used to interpret a controlled environment, consisting of a twodimensional board with paths. Movement and navigation decisions will be made possible by two DCmotorized wheels mounted on a platform, two simple computers and two...

Effects of acute or repeated paroxetine and fluoxetine treatment on affective behavior in male and female adolescent rats

Science.gov (United States)

Amodeo, Leslie R.; Greenfield, Venuz Y.; Humphrey, Danielle E.; Varela, Veronica; Pipkin, Joseph A.; Eaton, Shannon E.; Johnson, Jelesa D.; Plant, Christopher P.; Harmony, Zachary R.; Wang, Li; Crawford, Cynthia A.

2015-01-01

Rationale The SSRI antidepressant fluoxetine is one of the few drugs that is effective at treating depression in adolescent humans. In contrast, the SSRI paroxetine has limited efficacy and is more at risk for inducing suicidal behavior. Objective The purpose of the present study was to more fully characterize the differential actions of paroxetine and fluoxetine. Methods In Experiment 1, male and female rats were injected with paroxetine (2.5 or 10 mg/kg), fluoxetine (10 mg/kg), or vehicle for 10 days starting on postnatal day (PD) 35, and affective behaviors were assessed using sucrose preference and elevated plus maze tasks. A separate set of rats were used to examine monoamine levels. In Experiment 2, rats were injected with paroxetine (2.5, 5 or 10 mg/kg), fluoxetine (5, 10 or 20 mg/kg), or vehicle during the same time frame as Experiment 1 and anxiety-like behaviors were measured using elevated plus maze, light/dark box, and acoustic startle. Results Repeated SSRI treatment failed to alter sucrose preference, although both paroxetine and fluoxetine reduced time spent in the open arms of the elevated plus maze and light compartment of the light/dark box. Paroxetine, but not fluoxetine, enhanced acoustic startle and interfered with habituation. Serotonin turnover was decreased by both acute and repeated fluoxetine treatment but unaltered by paroxetine administration. Discussion These results show that repeated treatment with paroxetine and fluoxetine has dissociable actions in adolescent rats. In particular, paroxetine, but not fluoxetine, increases acoustic startle at low doses and may increase sensitivity to environmental stressors. PMID:26141193

Highly Palatable Food during Adolescence Improves Anxiety-Like Behaviors and Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Rats that Experienced Neonatal Maternal Separation

Directory of Open Access Journals (Sweden)

Jong-Ho Lee

2014-06-01

Full Text Available BackgroundThis study was conducted to examine the effects of ad libitum consumption of highly palatable food (HPF during adolescence on the adverse behavioral outcome of neonatal maternal separation.MethodsMale Sprague-Dawley pups were separated from dam for 3 hours daily during the first 2 weeks of birth (maternal separation, MS or left undisturbed (nonhandled, NH. Half of MS pups received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28 (MS+HPF. Pups were subjected to behavioral tests during young adulthood. The plasma corticosterone response to stress challenge was analyzed by radioimmunoassay.ResultsDaily caloric intake and body weight gain did not differ among the experimental groups. Ambulatory activities were decreased defecation activity and rostral grooming were increased in MS controls (fed with chow only compared with NH rats. MS controls spent less time in open arms, and more time in closed arms during the elevated plus maze test, than NH rats. Immobility duration during the forced swim test was increased in MS controls compared with NH rats. Cookie access normalized the behavioral scores of ambulatory and defecation activities and grooming, but not the scores during the elevated plus maze and swim tests in MS rats. Stress-induced corticosterone increase was blunted in MS rats fed with chow only, and cookie access normalized it.ConclusionProlonged access to HPF during adolescence and youth partly improves anxiety-related, but not depressive, symptoms in rats that experienced neonatal maternal separation, possibly in relation with improved function of the hypothalamic-pituitary-adrenal (HPA axis.

Zingiber officinale : evaulation of its Nootropic effect in mice | Joshi ...

African Journals Online (AJOL)

Ayurveda emphasizes use of herbs, nutraceuticals or life-style changes for controlling age related neurodegenerative disorders. The present study was undertaken to assess the potential of an ayurvedic rasayana (rejuvenator) drug Zingiber officinale Roscoe as a memory enhancer. Elevated plus maze and passive ...

The therapeutic potential of melatonin on neuronal function during ...

African Journals Online (AJOL)

(i.e. arms) in the Elevated plus Maze (EPM) task is shown in fig. 2a, 2b, 2c, and 2d. Melatonin ... Early melatonin intervention before rats reach old age is therefore .... Melanogaster by long-term supplementation with melatonin. Exp Gerontol;37 ...

Progesterone modulation of α5 nAChR subunits influences anxiety-related behavior during estrus cycle

OpenAIRE

Gangitano, David; Salas, Ramiro; Teng, Yanfen; Perez, Erika; De Biasi, Mariella

2009-01-01

Smokers often report an anxiolytic effect of cigarettes. In addition, stress-related disorders such as anxiety, post-traumatic stress syndrome, and depression are often associated with chronic nicotine use. To study the role of the α5 nicotinic acetylcholine receptor subunit in anxiety-related responses, control and α5 subunit null mice (α5 −/−) were subjected to the open field, light-dark box and elevated plus maze tests. In the open field and light-dark box, α5 −/− behaved like wild type co...

Food restriction affects Y-maze spatial recognition memory in developing mice.

Science.gov (United States)

Fu, Yu; Chen, Yanmei; Li, Liane; Wang, Yumei; Kong, Xiangyang; Wang, Jianhong

2017-08-01

The ambiguous effects of food restriction (FR) on cognition in rodents have been mostly explored in the aged brain by a variety of paradigms, in which either rewards or punishments are involved. This study aims to examine the effects of chronic and acute FR with varying intensities on spatial recognition memory in developing mice. We have used a Y-maze task that is based on the innate tendency of rodents to explore novel environments. In chronic FR, mice had 70-30% chow of control for seven weeks. In acute FR, mice were food restricted for 12-48h before the tests. We found that chronic FR had no effect on the preference of mice for novelty in the Y-maze, but severe FR (50-30% of control) caused impairment on spatial recognition memory. The impairment significantly correlated with the slow weight growth induced by FR. Acute FR also did not affect the novelty preference of mice, but either improved or impaired the memory retention. These data suggest chronic FR impairs Y-maze spatial recognition memory in developing mice depending on FR intensity and individual tolerability of the FR. Moreover, acute FR exerts diverse effects on the memory, either positive or negative. Our findings have revealed new insights on the effects of FR on spatial recognition memory in developing animals. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

The spatial distribution of errors made by rats in Hebb-Williams type mazes in relation to the spatial properties of the blind alleys

NARCIS (Netherlands)

Boer, S. de; Bohus, B.

The various configurations in series of Hebb-Williams type of mazes, which are used to measure problem solving behaviour in rats, differ markedly in structure. The relationship between error behaviour and spatial maze structure in control rats tested in a number of pharmacological experiments is

MK-801 and memantine act differently on short-term memory tested with different time-intervals in the Morris water maze test

Czech Academy of Sciences Publication Activity Database

Duda, W.; Wesierska, M.; Ostaszewski, P.; Valeš, Karel; Nekovářová, Tereza; Stuchlík, Aleš

2016-01-01

Roč. 311, Sep 15 (2016), s. 15-23 ISSN 0166-4328 R&D Projects: GA MŠk(CZ) LH14053; GA ČR(CZ) GA14-03627S Institutional support: RVO:67985823 Keywords : short-term memory * spatial working memory * memantine * dizocilpine * Morris water maze Subject RIV: FH - Neurology Impact factor: 3.002, year: 2016

Harmane induces anxiolysis and antidepressant-like effects in rats.

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Aricioglu, Feyza; Altunbas, Hale

2003-12-01

A forced swim test (FST) and an elevated plus maze (EPM) were used to determine antidepressant and anxiolytic effects of harmane in rats in comparison with a known antidepressant, imipramine (30 mg/kg i.p.). Harmane (2.5, 5.0, or 10 mg/kg, i.p.), saline, or imipramine were given 30 minutes before the tests. Administration of harmane decreased the time of immobility in the FST dose-dependently and increased the time spent in open arms in the EPM, as compared with the saline group. As an endogenous substance, harmane therefore has anti-anxiety and antidepressant effects.

Effects of Chronic Exposure to Ultrasound of Alternating Frequencies on the Levels of Aggression and Anxiety in CBA and BALB/c mice.

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Pavlov, D A; Gorlova, A V; Ushakova, V M; Zubkov, E A; Morozova, A Yu; Inozemtsev, A N; Chekhonin, V P

2017-08-01

Stress-induced changes in the behavior of CBA and BALB/c mice were studied after 3-week ultrasound exposure (22-45 kHz). The mice of both lines demonstrated increased aggression in the resident-intruder and social interest paradigms and reduced number of social interactions in the social interest test. Elevated plus maze test showed a decrease in anxiety level in CBA mice and an increase in this parameter in BALB/c mice. Chronic exposure to ultrasound induced an increase in aggression level in mice of both lines that was not directly related to changes in anxiety level.

Incremental Sentence Processing in Japanese: A Maze Investigation into Scrambled and Control Sentences

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Witzel, Jeffrey; Witzel, Naoko

2016-01-01

This study investigates preverbal structural and semantic processing in Japanese, a head-final language, using the maze task. Two sentence types were tested--simple scrambled sentences (Experiment 1) and control sentences (Experiment 2). Experiment 1 showed that even for simple, mono-clausal Japanese sentences, (1) there are online processing…

Young-Adult Male Rats’ Vulnerability to Chronic Mild Stress Is Reflected by Anxious-Like instead of Depressive-Like Behaviors

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Herrera-Pérez José Jaime

2016-01-01

Full Text Available In a previous study, we found that chronic mild stress (CMS paradigm did not induce anhedonia in young-adult male rats but it reduced their body weight gain. These contrasting results encouraged us to explore other indicators of animal’s vulnerability to stress such as anxious-like behaviors, since stress is an etiologic factor also for anxiety. Thus, in this study, we evaluated the vulnerability of these animals to CMS using behavioral tests of depression or anxiety and measuring serum corticosterone. Male Wistar rats were exposed to four weeks of CMS; the animals’ body weight and sucrose preference (indicator of anhedonia were assessed after three weeks, and, after the fourth week, some animals were evaluated in a behavioral battery (elevated plus maze, defensive burying behavior, and forced swimming tests; meanwhile, others were used to measure serum corticosterone. We found that CMS (1 did not affect sucrose preference, immobility behavior in the forced swimming test, or serum corticosterone; (2 decreased body weight gain; and (3 increased the rat’s entries into closed arms of the plus maze and the cumulative burying behavior. These data indicate that young male rats’ vulnerability to CMS is reflected as poor body weight gain and anxious-like instead of depressive-like behaviors.

Optimization of Apparatus Design and Behavioral Measures for the Assessment of Visuo-Spatial Learning and Memory of Mice on the Barnes Maze

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O'Leary, Timothy P.; Brown, Richard E.

2013-01-01

We have previously shown that apparatus design can affect visual-spatial cue use and memory performance of mice on the Barnes maze. The present experiment extends these findings by determining the optimal behavioral measures and test procedure for analyzing visuo-spatial learning and memory in three different Barnes maze designs. Male and female…

Penentuan Nilai Motorik Halus Anak Dengan Game Magic Maze Menggunakan Metode Mamdani

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Fadly, Muhammad

2015-01-01

Motor development is a very important factor in the development of the whole child. fine motor skills are very important because it affects the other terms of learning in early childhood. Therefore, it made the game Magic Maze to assess motor skills early childhood. Game Magic Maze in this study using Mamdani method in determining the values to a child's fine motor skills. Maze game will be made on the PC. 081402045

Maze Procedures for Atrial Fibrillation, From History to Practice.

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Kik, Charles; Bogers, Ad J J C

2011-10-01

Atrial fibrillation may result in significant symptoms, (systemic) thrombo-embolism, as well as tachycardia-induced cardiomyopathy with cardiac failure, and consequently be associated with significant morbidity and mortality. Nowadays symptomatic atrial fibrillation can be treated with catheter-based ablation, surgical ablation or hybrid approaches. In this setting a fairly large number of surgical approaches and procedures are described and being practised. It should be clear that the Cox-maze procedure resulted from building up evidence and experience in different steps, while some of the present surgical approaches and techniques are being based only on technical feasibility with limited experience, rather than on a process of consequent methodology. Some of the issues still under debate are whether or not the maze procedure can be limited to the left atrium or even to isolation of the pulmonary veins or that bi-atrial procedures are indicated, whether or not cardiopulmonary bypass is to be applied and which route of exposure facilitates an optimal result. In addition, maze procedures are not procedures guide by electrophysiological mapping. At least in theory not in all patients all lesions of the maze procedures are necessary. A history and aspects of current practise in surgical treatment of atrial fibrillation is presented.

The creativity maze

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Bourgeois-Bougrine, Samira; Glaveanu, Vlad Petre; Botella, Marion

2014-01-01

The present article aims to address a current gap in our understanding of creativity in screenplay writing by focusing on the cognitive, conative, affective, and environmental factors that come into play at different stages in the creative process. It reports a study employing in-depth interviews...... and or treatment), and, finally, intense periods of writing and rewriting the script. These 3 stages, and, in particular, the multiple and concrete decisions to be taken within each one of them, support a vision of the creative process in this domain metaphorically conceptualized as crossing a maze. Creators...

Behavioral Animal Model of the Emotional Response to Tinnitus and Hearing Loss.

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Lauer, Amanda M; Larkin, Gail; Jones, Aikeen; May, Bradford J

2018-02-01

Increased prevalence of emotional distress is associated with tinnitus and hearing loss. The underlying mechanisms of the negative emotional response to tinnitus and hearing loss remain poorly understood, and it is challenging to disentangle the emotional consequences of hearing loss from those specific to tinnitus in listeners experiencing both. We addressed these questions in laboratory rats using three common rodent anxiety screening assays: elevated plus maze, open field test, and social interaction test. Open arm activity in the elevated plus maze decreased substantially after one trial in controls, indicating its limited utility for comparing pre- and post-treatment behavior. Open field exploration and social interaction behavior were consistent across multiple sessions in control animals. Individual sound-exposed and salicylate-treated rats showed a range of phenotypes in the open field, including reduced entries into the center in some subjects and reduced locomotion overall. In rats screened for tinnitus, less locomotion was associated with higher tinnitus scores. In salicylate-treated animals, locomotion was correlated with age. Sound-exposed and salicylate-treated rats also showed reduced social interaction. These results suggest that open field exploratory activity is a selective measure for identifying tinnitus distress in individual animals, whereas social interaction reflects the general effects of hearing loss. This animal model will facilitate future studies of the structural and functional changes in the brain pathways underlying emotional distress associated with hearing dysfunction, as well as development of novel interventions to ameliorate or prevent negative emotional responses.

Exposure to a maternal cafeteria diet changes open-field behaviour in the developing offspring.

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Speight, Abigail; Davey, William G; McKenna, Emily; Voigt, Jörg-Peter W

2017-04-01

The early postnatal period is a sensitive period in rodents as behavioural systems are developing and maturing during this time. However, little is currently known about the behavioural effects of feeding a hyper-energetic cafeteria diet (CD) during the lactational period when offspring behaviour is tested during early adolescence. To this end, 23days old offspring from dams (Wistar) fed on CD during lactation were tested in either the open-field or the elevated plus-maze for exploration and anxiety-related behaviour. On postnatal day 9, maternal behaviour and non-maternal behaviour of the dam was assessed. It was hypothesized that lactational CD feeding would reduce anxiety in the offspring. CD-fed dams had a higher energy intake, due to an overconsumption of sugars and fats. When offspring from these dams were exposed to the open field after weaning, their locomotor activity was increased. They entered the more aversive inner zone of the open-field after a shorter latency, made more entries into and spent more time in the inner zone. Anxiety-related behaviour was not affected upon exposure to the elevated plus maze, suggesting anxiolysis in the open-field only. Increased maternal licking/grooming behaviour could possibly contribute to the anxiolytic phenotype as observed in the offspring from the CD group. In conclusion, we demonstrate that lactational overfeeding impacts on the development of behaviour in the early adolescent rat. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

Anxiogenic Like activity of Sarcocephalus latifolius Fruit Extract in Mice

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David Arome

2014-01-01

Full Text Available The use of pharmacological agents in the treatment of anxiety disorders have fallen out of favour as their unwanted side effects have become evident. The present challenges call for an inward look into harnessing the full potential of medicinal plants that abound around us. The present study evaluates the anxiogenic activity of ethanolic fruit extract of Sarcocephalus latifolius in mice. The prepared extract at 200, 400, and 600 mg/kg as well as 2.5 mg/kg of diazepam, the reference standard was administered orally. The anxiogenic activity of the extract was evaluated using elevated plus maze and open field models. In the elevated plus maze, the extract showed an anxiogenic effect in all the experimental dosage levels by decreasing the time spent and number within the open arms. Animals in the extract and physiological saline groups spent more time in the enclosed arms to avoid the open arms, probably to avoid falling off. The reference standard showed a significant (P

Protective effects of Punica granatum seeds extract against aging and scopolamine induced cognitive impairments in mice.

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Kumar, Sokindra; Maheshwari, Kamal Kishore; Singh, Vijender

2008-10-25

Dementia is one of the age related mental problems and characteristic symptom of various neurodegenerative diseases including Alzheimer's disease. This impairment probably is due to the vulnerability of the brain cells to increased oxidative stress during aging process. Many studies have shown that certain phenolic antioxidants attenuate neuronal cell death induced by oxidative stress. The present work was undertaken to assess the effect of ethanolic extract of Punica granatum seeds on cognitive performance of aged and scopolamine treated young mice using one trial step-down type passive avoidance and elevated plus maze task. Aged or scopolamine treated mice showed poor retention of memory in step-down type passive avoidance and in elevated plus maze task. Chronic administration (21 days) of Punica granatum extract and vitamin C significantly (p Punica granatum extract also significantly lowered lipid peroxidation level and increased antioxidant glutathione level in brain tissues. Punica granatum preparations could be protective in the treatment of cognitive disorders such as dementia and Alzheimer's disease.

Walkable self-overlapping virtual reality maze and map visualization demo

DEFF Research Database (Denmark)

Serubugo, Sule; Skantarova, Denisa; Evers, Nicolaj

2017-01-01

This paper describes our demonstration of a walkable self-overlapping maze and its corresponding map to facilitate asymmetric collaboration for room-scale virtual reality setups in public places.......This paper describes our demonstration of a walkable self-overlapping maze and its corresponding map to facilitate asymmetric collaboration for room-scale virtual reality setups in public places....

Anxiolytic effects of repeated treatment with an essential oil from Lippia alba and (R)-(-)-carvone in the elevated T-maze

International Nuclear Information System (INIS)

Hatano, V.Y.; Torricelli, A.S.; Giassi, A.C.C.; Coslope, L.A.; Viana, M.B.

2012-01-01

Lippia alba (Mill.) N.E. Brown (Verbenaceae) is widely used in different regions of Central and South America as a tranquilizer. The plant's anxiolytic properties, however, merit investigation. The present study evaluated the effects of repeated daily (14 days) intraperitoneal (ip) treatment with an essential oil (EO) from a chemotype of L. alba (LA, chemotype II, 12.5 and 25 mg/kg; N = 6-8) and (R)-(-)-carvone (25 mg/kg; N = 8-12), the main constituent of this chemotype, on male Wistar rats (weighing 250 g at the beginning of the experiments) submitted to the elevated T-maze (ETM). The ETM allows the measurement of two defensive responses: inhibitory avoidance and one-way escape. In terms of psychopathology, these responses have been related to generalized anxiety and panic disorder, respectively. Treatment with the EO impaired ETM avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (P < 0.05) (avoidance 2: control = 84.6 ± 35.2; EO 12.5 mg/kg = 11.8 ± 3.8; EO 25 mg/kg = 14.6 ± 2.7; diazepam = 7 ± 2.1). (R)-(-)-carvone also significantly altered this same response (P < 0.05; avoidance 1: control = 91.9 ± 31.5; carvone = 11.6 ± 1.8; diazepam = 8.1 ± 3.3). These results were not due to motor changes since no significant effects were detected in an open field. These observations suggest that LA exerts anxiolytic-like effects on a specific subset of defensive behaviors that have been implicated in generalized anxiety disorder, and suggest that carvone is one of the constituents of LA responsible for its action as a tranquilizer

Anxiolytic effects of repeated treatment with an essential oil from Lippia alba and (R)-(-)-carvone in the elevated T-maze

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Hatano, V.Y.; Torricelli, A.S. [Departamento de Biociências, Universidade Federal de São Paulo, Santos, SP (Brazil); Giassi, A.C.C. [Cellular and Molecular Medicine, University of Ottawa, Ottawa (Canada); Coslope, L.A. [Parque Nacional da Chapada Diamantina, Chapada Diamantina, BA (Brazil); Viana, M.B. [Departamento de Biociências, Universidade Federal de São Paulo, Santos, SP (Brazil)

2012-02-27

Lippia alba (Mill.) N.E. Brown (Verbenaceae) is widely used in different regions of Central and South America as a tranquilizer. The plant's anxiolytic properties, however, merit investigation. The present study evaluated the effects of repeated daily (14 days) intraperitoneal (ip) treatment with an essential oil (EO) from a chemotype of L. alba (LA, chemotype II, 12.5 and 25 mg/kg; N = 6-8) and (R)-(-)-carvone (25 mg/kg; N = 8-12), the main constituent of this chemotype, on male Wistar rats (weighing 250 g at the beginning of the experiments) submitted to the elevated T-maze (ETM). The ETM allows the measurement of two defensive responses: inhibitory avoidance and one-way escape. In terms of psychopathology, these responses have been related to generalized anxiety and panic disorder, respectively. Treatment with the EO impaired ETM avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (P < 0.05) (avoidance 2: control = 84.6 ± 35.2; EO 12.5 mg/kg = 11.8 ± 3.8; EO 25 mg/kg = 14.6 ± 2.7; diazepam = 7 ± 2.1). (R)-(-)-carvone also significantly altered this same response (P < 0.05; avoidance 1: control = 91.9 ± 31.5; carvone = 11.6 ± 1.8; diazepam = 8.1 ± 3.3). These results were not due to motor changes since no significant effects were detected in an open field. These observations suggest that LA exerts anxiolytic-like effects on a specific subset of defensive behaviors that have been implicated in generalized anxiety disorder, and suggest that carvone is one of the constituents of LA responsible for its action as a tranquilizer.

Participation of GABAA Chloride Channels in the Anxiolytic-Like Effects of a Fatty Acid Mixture

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Juan Francisco Rodríguez-Landa

2013-01-01

Full Text Available Human amniotic fluid and a mixture of eight fatty acids (FAT-M identified in this maternal fluid (C12:0, lauric acid, 0.9 μg%; C14:0, myristic acid, 6.9 μg%; C16:0, palmitic acid, 35.3 μg%; C16:1, palmitoleic acid, 16.4 μg%; C18:0, stearic acid, 8.5 μg%; C18:1cis, oleic acid, 18.4 μg%; C18:1trans, elaidic acid, 3.5 μg%; C18:2, linoleic acid, 10.1 μg% produce anxiolytic-like effects that are comparable to diazepam in Wistar rats, suggesting the involvement of γ-aminobutyric acid-A (GABAA receptors, a possibility not yet explored. Wistar rats were subjected to the defensive burying test, elevated plus maze, and open field test. In different groups, three GABAA receptor antagonists were administered 30 min before FAT-M administration, including the competitive GABA binding antagonist bicuculline (1 mg/kg, GABAA benzodiazepine antagonist flumazenil (5 mg/kg, and noncompetitive GABAA chloride channel antagonist picrotoxin (1 mg/kg. The FAT-M exerted anxiolytic-like effects in the defensive burying test and elevated plus maze, without affecting locomotor activity in the open field test. The GABAA antagonists alone did not produce significant changes in the behavioral tests. Picrotoxin but not bicuculline or flumazenil blocked the anxiolytic-like effect of the FAT-M. Based on the specific blocking action of picrotoxin on the effects of the FAT-M, we conclude that the FAT-M exerted its anxiolytic-like effects through GABAA receptor chloride channels.

Beneficial effects of fluoxetine, reboxetine, venlafaxine, and voluntary running exercise in stressed male rats with anxiety- and depression-like behaviors.

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Lapmanee, Sarawut; Charoenphandhu, Jantarima; Charoenphandhu, Narattaphol

2013-08-01

Rodents exposed to mild but repetitive stress may develop anxiety- and depression-like behaviors. Whether this stress response could be alleviated by pharmacological treatments or exercise interventions, such as wheel running, was unknown. Herein, we determined anxiety- and depression-like behaviors in restraint stressed rats (2h/day, 5 days/week for 4 weeks) subjected to acute diazepam treatment (30min prior to behavioral test), chronic treatment with fluoxetine, reboxetine or venlafaxine (10mg/kg/day for 4 weeks), and/or 4-week voluntary wheel running. In elevated plus-maze (EPM) and forced swimming tests (FST), stressed rats spent less time in the open arms and had less swimming duration than the control rats, respectively, indicating the presence of anxiety- and depression-like behaviors. Stressed rats also developed learned fear as evaluated by elevated T-maze test (ETM). Although wheel running could reduce anxiety-like behaviors in both EPM and ETM, only diazepam was effective in the EPM, while fluoxetine, reboxetine, and venlafaxine were effective in the ETM. Fluoxetine, reboxetine, and wheel running, but not diazepam and venlafaxine, also reduced depression-like behavior in FST. Combined pharmacological treatment and exercise did not further reduce anxiety-like behavior in stressed rats. However, stressed rats treated with wheel running plus reboxetine or venlafaxine showed an increase in climbing duration in FST. In conclusion, regular exercise (voluntary wheel running) and pharmacological treatments, especially fluoxetine and reboxetine, could alleviate anxiety- and depression-like behaviors in stressed male rats. Copyright © 2013 Elsevier B.V. All rights reserved.

Social defeat stress induces a depression-like phenotype in adolescent male c57BL/6 mice.

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Iñiguez, Sergio D; Riggs, Lace M; Nieto, Steven J; Dayrit, Genesis; Zamora, Norma N; Shawhan, Kristi L; Cruz, Bryan; Warren, Brandon L

2014-05-01

Abstract Exposure to stress is highly correlated with the emergence of mood-related illnesses. Because major depressive disorder often emerges in adolescence, we assessed the effects of social defeat stress on responses to depressive-like behaviors in juvenile mice. To do this, postnatal day (PD) 35 male c57BL/6 mice were exposed to 10 days of social defeat stress (PD35-44), while control mice were handled daily. Twenty-four hours after the last episode of defeat (PD45), separate groups of mice were tested in the social interaction, forced swimming, sucrose preference, and elevated plus-maze behavioral assays (n = 7-12 per group). Also, we examined body weight gain across days of social defeat and levels of blood serum corticosterone 40 min after the last episode of defeat stress. Our data indicates that defeated mice exhibited a depressive-like phenotype as inferred from increased social avoidance, increased immobility in the forced swim test, and reduced sucrose preference (a measure of anhedonia), when compared to non-defeated controls. Defeated mice also displayed an anxiogenic-like phenotype when tested on the elevated plus-maze. Lastly, stressed mice displayed lower body weight gain, along with increased blood serum corticosterone levels, when compared to non-stressed controls. Overall, we show that in adolescent male c57BL/6 mice, social defeat stress induces a depression- and anxiety-like phenotype 24 h after the last episode of stress. These data suggest that the social defeat paradigm may be used to examine the etiology of stress-induced mood-related disorders during adolescence.

The effects of juvenile stress on anxiety, cognitive bias and decision making in adulthood: a rat model.

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Nichola M Brydges

Full Text Available Stress experienced in childhood is associated with an increased risk of developing psychiatric disorders in adulthood. These disorders are particularly characterized by disturbances to emotional and cognitive processes, which are not currently fully modeled in animals. Assays of cognitive bias have recently been used with animals to give an indication of their emotional/cognitive state. We used a cognitive bias test, alongside a traditional measure of anxiety (elevated plus maze, to investigate the effects of juvenile stress (JS on adulthood behaviour using a rodent model. During the cognitive bias test, animals were trained to discriminate between two reward bowls based on a stimulus (rough/smooth sandpaper encountered before they reached the bowls. One stimulus (e.g. rough was associated with a lower value reward than the other (e.g. smooth. Once rats were trained, their cognitive bias was explored through the presentation of an ambiguous stimulus (intermediate grade sandpaper: a rat was classed as optimistic if it chose the bowl ordinarily associated with the high value reward. JS animals were lighter than controls, exhibited increased anxiety-like behaviour in the elevated plus maze and were more optimistic in the cognitive bias test. This increased optimism may represent an optimal foraging strategy for these underweight animals. JS animals were also faster than controls to make a decision when presented with an ambiguous stimulus, suggesting altered decision making. These results demonstrate that stress in the juvenile phase can increase anxiety-like behaviour and alter cognitive bias and decision making in adulthood in a rat model.

Spatial memory deficits in a virtual reality eight-arm radial maze in schizophrenia.

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Spieker, Elena A; Astur, Robert S; West, Jeffrey T; Griego, Jacqueline A; Rowland, Laura M

2012-03-01

Learning and memory impairments are present in schizophrenia (SZ) throughout the illness course and predict psychosocial function. Abnormalities in prefrontal and hippocampal function are thought to contribute to SZ deficits. The radial arm maze (RAM) is a test of spatial learning and memory in rodents that relies on intact prefrontal and hippocampal function. The goal of the present study was to investigate spatial learning in SZ using a virtual RAM. Thirty-three subjects with SZ and thirty-nine healthy controls (HC) performed ten trials of a virtual RAM task. Subjects attempted to learn to retrieve four rewards each located in separate arms. As expected, subjects with SZ used more time and traveled more distance to retrieve rewards, made more reference (RM) and working memory (WM) errors, and retrieved fewer rewards than HC. It is important to note that the SZ group did learn but did not reach the level of HC. Whereas RM errors decreased across trials in the SZ group, WM errors did not. There were no significant relationships between psychiatric symptom severity and maze performance. To our knowledge, use of a virtual 8-arm radial maze task in SZ to assess spatial learning is novel. Impaired virtual RAM performance in SZ is consistent with studies that examined RAM performance in animal models of SZ. Results provide further support for compromised prefrontal and hippocampal function underlying WM and RM deficits in SZ. The virtual RAM task could help bridge preclinical and clinical research for testing novel drug treatments of SZ. Copyright © 2011 Elsevier B.V. All rights reserved.

Results of clinical application of the modified maze procedure as concomitant surgery

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Bakker, Robbert C.; Akin, Sakir; Rizopoulos, Dimitris; Kik, Charles; Takkenberg, Johanna J.M.; Bogers, Ad J.J.C.

2013-01-01

OBJECTIVES Atrial fibrillation is the most common cardiac arrhythmia and is associated with significant morbidity and mortality. The classic cut-and-sew maze procedure is successful in 85–95% of patients. However, the technical complexity has prompted modifications of the maze procedure. The objective of this study was to retrospectively evaluate the clinical safety and efficacy of the maze treatment performed at our institution. METHODS From March 2001 until February 2009, 169 patients underwent a modified maze procedure for atrial fibrillation at the Erasmus MC, Rotterdam. Patient characteristics, surgical procedure and follow-up data were obtained by reviewing the medical charts and consulting with the referring physicians. The efficacy of the procedure as measured by AF recurrence was analysed with a repeated measurements model. The quality of life of the patients was assessed with the SF-36 (a short-form health survey with 36 questions) questionnaire and compared with that of the general Dutch population. RESULTS Of the 169 patients who underwent a modified maze procedure, 163 had their maze procedure as a concomitant procedure. The 30-day mortality rate was 4.7% (n = 8). The rate of post-procedural AF recurrence varied significantly over time (P < 0.0001). Decreased left ventricular function, increased age and higher preoperative creatinine levels were predictors of AF recurrence. Quality of life, as measured with the SF-36 questionnaire, was comparable with that of the Dutch population for all health domains. CONCLUSIONS Concomitant maze is a relatively safe treatment that eliminates atrial fibrillation in the majority of patients, although the probability of recurrent AF increases with the passage of time. Decreased left ventricular function, increased age and higher preoperative creatinine levels are associated with an increased risk of AF recurrence. PMID:23103720

Similar reliability and equivalent performance of female and male mice in the open field and water‐maze place navigation task

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Fritz, Ann‐Kristina; Amrein, Irmgard

2017-01-01

Although most nervous system diseases affect women and men differentially, most behavioral studies using mouse models do not include subjects of both sexes. Many researchers worry that data of female mice may be unreliable due to the estrous cycle. Here, we retrospectively evaluated sex effects on coefficient of variation (CV) in 5,311 mice which had performed the same place navigation protocol in the water‐maze and in 4,554 mice tested in the same open field arena. Confidence intervals for Cohen's d as measure of effect size were computed and tested for equivalence with 0.2 as equivalence margin. Despite the large sample size, only few behavioral parameters showed a significant sex effect on CV. Confidence intervals of effect size indicated that CV was either equivalent or showed a small sex difference at most, accounting for less than 2% of total group to group variation of CV. While female mice were potentially slightly more variable in water‐maze acquisition and in the open field, males tended to perform less reliably in the water‐maze probe trial. In addition to evaluating variability, we also directly compared mean performance of female and male mice and found them to be equivalent in both water‐maze place navigation and open field exploration. Our data confirm and extend other large scale studies in demonstrating that including female mice in experiments does not cause a relevant increase of data variability. Our results make a strong case for including mice of both sexes whenever open field or water‐maze are used in preclinical research. PMID:28654717

Effect of soybean supplementation on the memory of alprazolam-induced amnesic mice

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Nitin Bansal

2010-01-01

Full Text Available Soybean, Glycine max (L. Merr. (Leguminoseae, is known as golden bean. It contains vegetable protein, oligosaccharide, dietary fiber, vitamins, isoflavones and minerals. Earlier studies have demonstrated a cholesterol lowering, skin protective, antitumour, antidiabetic and antioxidative potential of soybean. Soy isoflavones are also utilized as estrogen replacement therapy in postmenopausal women. The present study was undertaken to investigate the effect of soybean on memory of mice when consumed along with diet. Soybean was administered chronically for 60 consecutive days as three soybean diets viz. Soy2, Soy5, Soy10. These diet contains soybean in normal diet at concentration of 2%, 5%, 10% w/w respectively. Passive avoidance paradigm and elevated plus maze served as exteroceptive behavioral models for testing memory. Alprazolam (0.5 mg/kg; i.p. induced amnesia served as interoceptive behavioral model. The administration of soybean significantly reversed alprazolam-induced amnesia in a dose-dependent manner as indicated by the increased step down latency of mice using passive avoidance paradigm and increased transfer latency using elevated plus maze. Theses results suggest that consumption of soybean in diet may not only improve memory but also reverse the memory deficits, owing to its multifarious activities. It would be worthwhile to explore the potential of this nutrient in the management of Alzheimer′s disease.

Dietary arginine depletion reduces depressive-like responses in male, but not female, mice.

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Workman, Joanna L; Weber, Michael D; Nelson, Randy J

2011-09-30

Previous behavioral studies have manipulated nitric oxide (NO) production either by pharmacological inhibition of its synthetic enzyme, nitric oxide synthase (NOS), or by deletion of the genes that code for NOS. However manipulation of dietary intake of the NO precursor, L-arginine, has been understudied in regard to behavioral regulation. L-Arginine is a common amino acid present in many mammalian diets and is essential during development. In the brain L-arginine is converted into NO and citrulline by the enzyme, neuronal NOS (nNOS). In Experiment 1, paired mice were fed a diet comprised either of an L-arginine-depleted, L-arginine-supplemented, or standard level of L-arginine during pregnancy. Offspring were continuously fed the same diets and were tested in adulthood in elevated plus maze, forced swim, and resident-intruder aggression tests. L-Arginine depletion reduced depressive-like responses in male, but not female, mice and failed to significantly alter anxiety-like or aggressive behaviors. Arginine depletion throughout life reduced body mass overall and eliminated the sex difference in body mass. Additionally, arginine depletion significantly increased corticosterone concentrations, which negatively correlated with time spent floating. In Experiment 2, adult mice were fed arginine-defined diets two weeks prior to and during behavioral testing, and again tested in the aforementioned tests. Arginine depletion reduced depressive-like responses in the forced swim test, but did not alter behavior in the elevated plus maze or the resident intruder aggression test. Corticosterone concentrations were not altered by arginine diet manipulation in adulthood. These results indicate that arginine depletion throughout development, as well as during a discrete period during adulthood ameliorates depressive-like responses. These results may yield new insights into the etiology and sex differences of depression. Copyright © 2011 Elsevier B.V. All rights reserved.

Behavioral changes induced by cocaine in mice are modified by a hyperlipidic diet or recombinant leptin

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E. Erhardt

2006-12-01

Full Text Available The objective of the present study was to determine if the acute behavioral effects of cocaine acutely administered intraperitoneally (ip at doses of 5, 10 and 20 mg/kg on white male CF1 mice, 90 days of age, would be influenced by leptin acutely administered ip (at doses of 5, 10 and 20 µg/kg or by endogenous leptin production enhanced by a high-fat diet. The acute behavioral effects of cocaine were evaluated in open-field, elevated plus-maze and forced swimming tests. Results were compared between a group of 80 mice consuming a balanced diet and a high-fat diet, and a group of 80 mice fed a commercially available rodent chow formula (Ralston Purina but receiving recombinant leptin (rLeptin or saline ip. Both the high-fat-fed and rLeptin-treated mice showed decreased locomotion in the open-field test, spent more time in the open arms of the elevated plus-maze and showed less immobility time in the forced swimming test (F(1,68 = 7.834, P = 0.007. There was an interaction between diets and cocaine/saline treatments in locomotion (F(3,34 = 3.751, P = 0.020 and exploration (F(3,34 = 3.581, P = 0.024. These results suggest that anxiolytic effects and increased general activity were induced by leptin in cocaine-treated mice and that low leptin levels are associated with behavioral depression. Chronic changes in diet composition producing high leptin levels or rLeptin treatment may result in an altered response to cocaine in ethologic tests that measure degrees of anxiety and depression, which could be attributed to an antagonistic effect of leptin.

Effects of the estrous cycle and ovarian hormones on behavioral indices of anxiety in female rats.

Science.gov (United States)

Mora, S; Dussaubat, N; Díaz-Véliz, G

1996-10-01

The influence of the estrous cycle and the effects of exogenous administration of estradiol and progesterone on level of anxiety were studied in intact and ovariectomized rats. Intact Sprague-Dawley female rats were classified according to the stages of estrous cycle. Another group of rats was ovariectomized bilaterally and, 14 days after surgery, they received estradiol benzoate (10 micrograms/kg, s.c.) and/or progesterone (25 mg/kg, s.c.) or corn oil (1 ml/kg). The behavioral tests began 3 h after estradiol or 6 h after progesterone and consisted of: (1) exploration of an elevated plus-maze; and (2) retention of a passive avoidance response. Open-arm exploration of the plus-maze varied according to light intensity and the stages of the estrous cycle. There was a slight increase in open-arm exploration by rats in metestrus, under high light intensity. Low light intensity increased the exploration of the open arms by rats in proestrus and estrus, compared to the other phases of the cycle. Retention of the passive avoidance response was inhibited during proestrus and estrus. Progesterone increased open-arm exploration of the plus-maze under high light conditions, whereas estradiol antagonized this effect. Retention of passive avoidance was inhibited after estradiol or progesterone injection. These results suggest that the behavioral indices of anxiety can vary across the estrous cycle, that low light intensities have anxiolytic-like effects, and that the sensitivity to this effect is higher during proestrus and estrus. This could be explained through modulatory effects of ovarian hormones upon behavioral indices of anxiety.

Navigation using sensory substitution in real and virtual mazes.

Science.gov (United States)

Chebat, Daniel-Robert; Maidenbaum, Shachar; Amedi, Amir

2015-01-01

Under certain specific conditions people who are blind have a perception of space that is equivalent to that of sighted individuals. However, in most cases their spatial perception is impaired. Is this simply due to their current lack of access to visual information or does the lack of visual information throughout development prevent the proper integration of the neural systems underlying spatial cognition? Sensory Substitution devices (SSDs) can transfer visual information via other senses and provide a unique tool to examine this question. We hypothesize that the use of our SSD (The EyeCane: a device that translates distance information into sounds and vibrations) can enable blind people to attain a similar performance level as the sighted in a spatial navigation task. We gave fifty-six participants training with the EyeCane. They navigated in real life-size mazes using the EyeCane SSD and in virtual renditions of the same mazes using a virtual-EyeCane. The participants were divided into four groups according to visual experience: congenitally blind, low vision & late blind, blindfolded sighted and sighted visual controls. We found that with the EyeCane participants made fewer errors in the maze, had fewer collisions, and completed the maze in less time on the last session compared to the first. By the third session, participants improved to the point where individual trials were no longer significantly different from the initial performance of the sighted visual group in terms of errors, time and collision.

Beta-hydroxy-beta-methylbutyrate (HMB) ameliorates age-related deficits in water maze performance, especially in male rats.

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Kougias, Daniel G; Hankosky, Emily R; Gulley, Joshua M; Juraska, Janice M

2017-03-01

Beta-hydroxy-beta-methylbutyrate (HMB) is commonly supplemented to maintain muscle in elderly and clinical populations and has potential as a nootropic. Previously, we have shown that in both male and female rats, long-term HMB supplementation prevents age-related dendritic shrinkage within the medial prefrontal cortex (mPFC) and improves cognitive flexibility and working memory performance that are both age- and sex-specific. In this study, we further explore the cognitive effects by assessing visuospatial learning and memory with the Morris water maze. Female rats were ovariectomized at 11months of age to model human menopause. At 12months of age, male and female rats received relatively short- or long-term (1- or 7-month) dietary HMB (450mg/kg/dose) supplementation twice a day prior to testing. Spatial reference learning and memory was assessed across four days in the water maze with four trials daily and a probe trial on the last day. Consistent with previous work, there were age-related deficits in water maze performance in both sexes. However, these deficits were ameliorated in HMB-treated males during training and in both sexes during probe trial performance. Thus, HMB supplementation prevented the age-related decrement in water maze performance, especially in male rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Investigation of antidepressant-like and anxiolytic-like actions and cognitive and motor side effects of four N-methyl-D-aspartate receptor antagonists in mice

DEFF Research Database (Denmark)

Refsgaard, Louise Konradsen; Pickering, Darryl S; Andreasen T., Jesper

2017-01-01

antagonists. MK-801, ketamine, S-ketamine, RO 25-6981 and the positive control, citalopram, were tested for antidepressant-like and anxiolytic-like effects in mice using the forced-swim test, the elevated zero maze and the novelty-induced hypophagia test. Side effects were assessed using a locomotor activity...... test, the modified Y-maze and the rotarod test. All compounds increased swim distance in the forced-swim test. In the elevated zero maze, the GluN2B subtype-selective RO 25-6981 affected none of the measured parameters, whereas all other compounds showed anxiolytic-like effects. In the novelty......-induced hypophagia test, citalopram and MK-801 showed anxiogenic-like action. All NMDAR antagonists induced hyperactivity. The high doses of ketamine and MK-801 impaired performance in the modified Y-maze test, whereas S-ketamine and RO 25-6891 showed no effects in this test. Only MK-801 impaired rotarod performance...

Discussion on the optimization design on mazes of medical linear accelerator facilities

International Nuclear Information System (INIS)

Cao Lei; Zhang Wenyi; Liu Baiqun; Hou Changsong; Zhao Lancai

2007-01-01

Objective: To discuss the differences on the design and evaluation between the L-type and Z-type mazes of typical medical electric linear accelerator. Methods: The study is conducted by choosing some typical medical electric linear accelerators used in China, further analyzing on the running conditions of the accelerators in the mode of MV-X-ray, and referring to the late NCRP Report 51 and other references. Results: The radiation levels at the access to therapy room are effectively reduced by Z-type mazes. Conclusions: The Z-type mazes are advisable during the optimization design. (authors)

Withaferin-A displays enhanced anxiolytic efficacy without tolerance ...

African Journals Online (AJOL)

Withaferin-A dose-dependently (10 tob40 mg/kg) displayed anxiolytic activity, as measured by an increase in open arm exploration time in the elevated plus-maze (EPM), following intraperitoneal (i.p.) administration in rats. Acute administration of withaferin-A at 40.0 mg/kg significantly (P<0.05) increased open arm ...

Similar reliability and equivalent performance of female and male mice in the open field and water-maze place navigation task.

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Fritz, Ann-Kristina; Amrein, Irmgard; Wolfer, David P

2017-09-01

Although most nervous system diseases affect women and men differentially, most behavioral studies using mouse models do not include subjects of both sexes. Many researchers worry that data of female mice may be unreliable due to the estrous cycle. Here, we retrospectively evaluated sex effects on coefficient of variation (CV) in 5,311 mice which had performed the same place navigation protocol in the water-maze and in 4,554 mice tested in the same open field arena. Confidence intervals for Cohen's d as measure of effect size were computed and tested for equivalence with 0.2 as equivalence margin. Despite the large sample size, only few behavioral parameters showed a significant sex effect on CV. Confidence intervals of effect size indicated that CV was either equivalent or showed a small sex difference at most, accounting for less than 2% of total group to group variation of CV. While female mice were potentially slightly more variable in water-maze acquisition and in the open field, males tended to perform less reliably in the water-maze probe trial. In addition to evaluating variability, we also directly compared mean performance of female and male mice and found them to be equivalent in both water-maze place navigation and open field exploration. Our data confirm and extend other large scale studies in demonstrating that including female mice in experiments does not cause a relevant increase of data variability. Our results make a strong case for including mice of both sexes whenever open field or water-maze are used in preclinical research. © 2017 The Authors. American Journal of Medical Genetics Part C Published by Wiley Periodicals, Inc.

Downtown People Mover (DPM) Winterization Test Demonstration : Otis Elevator

Science.gov (United States)

1982-01-01

The Otis Elevator Company Transportation Technology Division (OTIS-TTD) Downtown People Mover (DPM) Winterization Test Demonstration Final Report covers the 1978-79 and 1979-80 winter periods. Tests were performed at the Otis test track in Denver, Co...

Shielding of radiation fields generated by 252Cf in a concrete maze. Part 2 -- Simulation

International Nuclear Information System (INIS)

Fasso, A.; Ipe, N.E.; Reyna, A.

1998-03-01

A streaming experiment performed in a concrete maze of shape and size typical of a radiotherapy room was simulated with the Monte Carlo program FLUKA. The purpose of the calculation was to test the performance of the code in the low energy neutron range, and at the same time to provide additional information which could help in optimizing shielding of medical facilities. Instrument responses were calculated at different maze locations for several experimental configurations and were compared with measurements. In addition, neutron and gamma fluence, ambient dose equivalent and effective dose were calculated at the same positions. Both sources used in the experiment, namely a bare 252 Cf source and one shielded by a tungsten shell 5 cm thick, were considered in the simulation

Anomalies in social behaviors and exploratory activities in an APPswe/PS1 mouse model of Alzheimer's disease.

Science.gov (United States)

Filali, Mohammed; Lalonde, Robert; Rivest, Serge

2011-10-24

Alzheimer's disease is characterized by deficits in social communication, associated with generalized apathy or agitation, as well as social memory. To assess social behaviors in 6-month-old male APPswe/PS1 bigenics relative to non-transgenic controls, the 3-chamber test was used, together with open-field and elevated plus-maze tests of exploration. APPswe/PS1 mice were less willing to engage in social interaction than wild-type, avoiding an unfamiliar stimulus mouse, probably not due to generalized apathy because in both tests of exploratory activity the mutants were hyperactive. This study reveals reduced "sociability" combined with hyperactivity in an APPswe/PS1 mouse model of Alzheimer dementia. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of repeated asenapine in a battery of tests for anxiety-like behaviours in mice.

Science.gov (United States)

Ene, Hila M; Kara, Nirit Z; Barak, Noa; Reshef Ben-Mordechai, Tal; Einat, Haim

2016-04-01

A number of atypical antipsychotic drugs were demonstrated to have anxiolytic effects in patients and in animal models. These effects were mostly suggested to be the consequence of the drugs' affinity to the serotonin system and its receptors. Asenapine is a relatively new atypical antipsychotic that is prescribed for schizophrenia and for bipolar mania. Asenapine has a broad pharmacological profile with significant effects on serotonergic receptors, hence it is reasonable to expect that asenapine may have some anxiolytic effects. The present study was therefore designed to examine possible effects of asenapine on anxiety-like behaviour of mice. Male ICR mice were repeatedly treated with 0.1 or 0.3 mg/kg injections of asenapine and then tested in a battery of behavioural tests related to anxiety including the open-field test, elevated plus-maze (EPM), defensive marble burying and hyponeophagia tests. In an adjunct experiment, we tested the effects of acute diazepam in the same test battery. The results show that diazepam reduced anxiety-like behaviour in the EPM, the defensive marble burying test and the hyponeophagia test but not in the open field. Asenapine has anxiolytic-like effects in the EPM and the defensive marble burying tests but had no effects in the open-field or the hyponeophagia tests. Asenapine had no effects on locomotor activity. The results suggest that asenapine may have anxiolytic-like properties and recommends that clinical trials examining such effects should be performed.

Navigation using sensory substitution in real and virtual mazes.

Directory of Open Access Journals (Sweden)

Daniel-Robert Chebat

Full Text Available Under certain specific conditions people who are blind have a perception of space that is equivalent to that of sighted individuals. However, in most cases their spatial perception is impaired. Is this simply due to their current lack of access to visual information or does the lack of visual information throughout development prevent the proper integration of the neural systems underlying spatial cognition? Sensory Substitution devices (SSDs can transfer visual information via other senses and provide a unique tool to examine this question. We hypothesize that the use of our SSD (The EyeCane: a device that translates distance information into sounds and vibrations can enable blind people to attain a similar performance level as the sighted in a spatial navigation task. We gave fifty-six participants training with the EyeCane. They navigated in real life-size mazes using the EyeCane SSD and in virtual renditions of the same mazes using a virtual-EyeCane. The participants were divided into four groups according to visual experience: congenitally blind, low vision & late blind, blindfolded sighted and sighted visual controls. We found that with the EyeCane participants made fewer errors in the maze, had fewer collisions, and completed the maze in less time on the last session compared to the first. By the third session, participants improved to the point where individual trials were no longer significantly different from the initial performance of the sighted visual group in terms of errors, time and collision.

Differential behavioral outcomes of 3,4-methylenedioxymethamphetamine (MDMA-ecstasy in anxiety-like responses in mice

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V. Ferraz-de-Paula

2011-05-01

Full Text Available Anxiolytic and anxiogenic-like behavioral outcomes have been reported for methylenedioxymethamphetamine (MDMA or ecstasy in rodents. In the present experiment, we attempted to identify behavioral, hormonal and neurochemical outcomes of MDMA treatment to clarify its effects on anxiety-related responses in 2-month-old Balb/c male mice (25-35 g; N = 7-10 mice/group. The behavioral tests used were open field, elevated plus maze, hole board, and defensive behavior against predator odor. Moreover, we also determined striatal dopamine and dopamine turnover, and serum corticosterone levels. MDMA was injected ip at 0.2, 1.0, 5.0, 8.0, 10, or 20 mg/kg. MDMA at 10 mg/kg induced the following significant (P < 0.05 effects: a a dose-dependent increase in the distance traveled and in the time spent moving in the open field; b decreased exploratory activity in the hole board as measured by number of head dips and time spent in head dipping; c increased number of open arm entries and increased time spent in open arm exploration in the elevated plus maze; d increased time spent away from an aversive stimulus and decreased number of risk assessments in an aversive odor chamber; e increased serum corticosterone levels, and f increased striatal dopamine level and turnover. Taken together, these data suggest an anxiogenic-like effect of acute MDMA treatment, despite the fact that behavioral anxiety expression was impaired in some of the behavioral tests used as a consequence of the motor stimulating effects of MDMA.

Preclinical animal anxiety research - flaws and prejudices.

Science.gov (United States)

Ennaceur, Abdelkader; Chazot, Paul L

2016-04-01

The current tests of anxiety in mice and rats used in preclinical research include the elevated plus-maze (EPM) or zero-maze (EZM), the light/dark box (LDB), and the open-field (OF). They are currently very popular, and despite their poor achievements, they continue to exert considerable constraints on the development of novel approaches. Hence, a novel anxiety test needs to be compared with these traditional tests, and assessed against various factors that were identified as a source of their inconsistent and contradictory results. These constraints are very costly, and they are in most cases useless as they originate from flawed methodologies. In the present report, we argue that the EPM or EZM, LDB, and OF do not provide unequivocal measures of anxiety; that there is no evidence of motivation conflict involved in these tests. They can be considered at best, tests of natural preference for unlit and/or enclosed spaces. We also argued that pharmacological validation of a behavioral test is an inappropriate approach; it stems from the confusion of animal models of human behavior with animal models of pathophysiology. A behavioral test is developed to detect not to produce symptoms, and a drug is used to validate an identified physiological target. In order to overcome the major methodological flaws in animal anxiety studies, we proposed an open space anxiety test, a 3D maze, which is described here with highlights of its various advantages over to the traditional tests.

Activation of the hippocampal complex during tactile maze solving in congenitally blind subjects

DEFF Research Database (Denmark)

Gagnon, Léa; Schneider, Fabien C; Siebner, Hartwig R

2012-01-01

Despite their lack of vision, congenitally blind subjects are able to build and manipulate cognitive maps for spatial navigation. It is assumed that they thereby rely more heavily on echolocation, proprioceptive signals and environmental cues such as ambient temperature and audition to compensate...... imaging (fMRI) in congenitally blind and blindfolded sighted participants while they navigated through a tactile multiple T-maze. Both groups learned the maze task at a similar pace. In blind participants, tactile maze navigation was associated with increased BOLD responses in the right hippocampus...

Overexpression of CRF in the BNST diminishes dysphoria but not anxiety-like behavior in nicotine withdrawing rats.

Science.gov (United States)

Qi, Xiaoli; Guzhva, Lidia; Yang, Zhihui; Febo, Marcelo; Shan, Zhiying; Wang, Kevin K W; Bruijnzeel, Adriaan W

2016-09-01

Smoking cessation leads to dysphoria and anxiety, which both increase the risk for relapse. This negative affective state is partly mediated by an increase in activity in brain stress systems. Recent studies indicate that prolonged viral vector-mediated overexpression of stress peptides diminishes stress sensitivity. Here we investigated whether the overexpression of corticotropin-releasing factor (CRF) in the bed nucleus of the stria terminalis (BNST) diminishes nicotine withdrawal symptoms in rats. The effect of nicotine withdrawal on brain reward function was investigated with an intracranial self-stimulation (ICSS) procedure. Anxiety-like behavior was investigated in the elevated plus maze test and a large open field. An adeno-associated virus (AAV) pseudotype 2/5 vector was used to overexpress CRF in the lateral BNST and nicotine dependence was induced using minipumps. Administration of the nicotinic receptor antagonist mecamylamine and cessation of nicotine administration led to a dysphoria-like state, which was prevented by the overexpression of CRF in the BNST. Nicotine withdrawal also increased anxiety-like behavior in the elevated plus maze test and large open field test and slightly decreased locomotor activity in the open field. The overexpression of CRF in the BNST did not prevent the increase in anxiety-like behavior or decrease in locomotor activity. The overexpression of CRF increased CRF1 and CRF2 receptor gene expression and increased the CRF2/CRF1 receptor ratio. In conclusion, the overexpression of CRF in the BNST prevents the dysphoria-like state associated with nicotine withdrawal and increases the CRF2/CRF1 receptor ratio, which may diminish the negative effects of CRF on mood. Published by Elsevier B.V.

Chemical composition and anxiolytic-like effects of the Bauhinia platypetala

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Francisco José Borges dos Santos

2012-01-01

Full Text Available The pantropical genus Bauhinia, Fabaceae, known popularly as cow's foot, is widely used in folk medicine as antidiabetic. Behavioral effects of the ethanolic extract and ethereal, aqueous and ethyl acetate fractions from B. platypetala Benth. ex Hemsl. leaves were studied in male Swiss mice. The ethanolic extract and fractions were administered intraperitoneally and its effects on spontaneous motor activity (total motility, locomotion, rearing and grooming behavior were monitored. Anxiolytic-like properties were studied in the elevated plus-maze test and the possible antidepressant-like actions were evaluated in the forced swimming test. The results revealed that only the highest dose of the ethereal fraction (50 mg/kg, i.p. caused a significant decrease in total motility, locomotion and rearing. Sole dose injected (50 mg/kg of ethanolic extract and ethereal fractions increased the exploration of the elevated plus-maze open arms in a similar way to that of diazepam (2 mg/kg, i.p.. In the forced swimming test, the ethanolic extract and their fractions (12.5, 25 or 50 mg/kg was not as effective as paroxetine (10 or 20 mg/kg, i.p. and imipramine (25 or 50 mg/kg, i.p. in reducing immobility. These results suggest that some of the components of the ethanolic extract and of the ethereal fraction from B. platypetala, such as p-cymene, phytol, D-lactic acid, hexadecanoic acid, among others, may have anxiolytic-like properties, which deserve further investigation. Furthermore, the results obtained indicate that ethanolic extract from B. platypetala and their fractions do not present antidepressive properties. However, these properties cannot be related to the chemical constituents identified in this specie.

Behavioural and neurotoxic effects of ayahuasca infusion (Banisteriopsis caapi and Psychotria viridis) in female Wistar rat.

Science.gov (United States)

Pic-Taylor, Aline; da Motta, Luciana Gueiros; de Morais, Juliana Alves; Junior, Willian Melo; Santos, Alana de Fátima Andrade; Campos, Leandro Ambrósio; Mortari, Marcia Renata; von Zuben, Marcus Vinicius; Caldas, Eloisa Dutra

2015-09-01

Ayahuasca, a psychoactive beverage used by indigenous and religious groups, is generally prepared by the coction of Psychotria viridis and Banisteriopsis caapi plants containing N,N-dimethyltryptamine (DMT) and β-carboline alkaloids, respectively. To investigate the acute toxicity of ayahuasca, the infusion was administered by gavage to female Wistar rats at doses of 30X and 50X the dose taken during a religious ritual, and the animals observed for 14 days. Behavioural functions were investigated one hour after dosing at 15X and 30X using the open field, elevated plus maze, and forced swimming tests. Neuronal activation (c-fos marked neurons) and toxicity (Fluoro-Jade B and Nissl/Cresyl staining) were investigated in the dorsal raphe nuclei (DRN), amygdaloid nucleus, and hippocampal formation brain areas of rats treated with a 30X ayahuasca dose. The actual lethal oral dose in female Wistar rats could not be determined in this study, but was shown to be higher than the 50X (which corresponds to 15.1mg/kg bw DMT). The ayahuasca and fluoxetine treated groups showed a significant decrease in locomotion in the open field and elevated plus-maze tests compared to controls. In the forced swimming test, ayahuasca treated animals swam more than controls, a behaviour that was not significant in the fluoxetine group. Treated animals showed higher neuronal activation in all brain areas involved in serotoninergic neurotransmission. Although this led to some brain injury, no permanent damage was detected. These results suggest that ayahuasca has antidepressant properties in Wistar female at high doses, an effect that should be further investigated. Copyright © 2015 Elsevier B.V. All rights reserved.

In vitro testing of daptomycin plus rifampin againstmethicillin-resistant Staphylococcus aureus resistant to rifampin

International Nuclear Information System (INIS)

Khaswneh, Faisal A.; Ashcraft, Deborah S.; Pankey, George A.

2008-01-01

Objective was to test for synergy between daptomycin (DAP) and rifampin(RIF) against RIF-resistant methicillin-resistant Staphylococcus aureus(MRSA) isolates. Synergy testing using time-kill assay (TKA) was performed on6 clinically and genetically unique RIF-resistant MRSA isolates. The isolateswere identified out of 489 (1.2%) samples collected during April 2003 toAugust 2006, from patients at the Ochsner Medical Center in New Orleans,Louisiana, United States of America. Synergy testing of DAP plus RIF by TKAshowed that 5 isolates were different, but one isolate was antagonistic. Ourin-vitro study failed to demonstrate synergy between DAP plus RIF, againstour RIF-resistant MRSA isolates. Clinical failure of this combination shouldprompt the clinician to consider antagonism as one of the potential causes.(author)

Aspartame and the hippocampus: Revealing a bi-directional, dose/time-dependent behavioural and morphological shift in mice.

Science.gov (United States)

Onaolapo, Adejoke Y; Onaolapo, Olakunle J; Nwoha, Polycarp U

2017-03-01

Changes, in behaviour, oxidative markers of stress and hippocampal morphology were evaluated following aspartame administration. Mice, (20-22g each) were given vehicle (10ml/kg) or aspartame (20, 40, 80 and 160mg/kg) daily for 28days. They were tested in the Y-maze, radial-arm maze and elevated plus-maze (EPM) after the first and last dose of vehicle or aspartame; and then sacrificed. Hippocampal slices were analysed for aspartic acid, nitric oxide (NO) and superoxide dismutase (SOD); and processed for general histology and neuritic plaques. Glial fibrillary-acid protein (GFAP) expression and neuron-specific enolase (NSE) activities were determined. Radial-arm maze scores increased significantly after acute administration at 80 and 160mg/kg. Repeated administration at 20 and 40mg/kg (Y-maze) and at 40mg/kg (radial-arm maze) was also associated with increased scores, however, performance decreased at higher doses. EPM tests revealed anxiogenic responses following both acute and repeated administration. Significant increase in SOD and NO activities were observed at 40, 80 and 160mg/kg. Neuron counts reduced at higher doses of aspartame. At 40, 80 and 160mg/kg, fewer GFAP-reactive astrocytes were observed in the cornus ammonis, but increased GFAP-reactivity was observed in the dentate gyrus subgranular zone. NSE-positive neurons were readily identifiable within the dentate gyrus at the lower doses of aspartame; but at 160mg/kg, there was marked neuron loss and reduction in NSE-positive neurons. Oral aspartame significantly altered behaviour, anti-oxidant status and morphology of the hippocampus in mice; also, it may probably trigger hippocampal adult neurogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of early life trauma are dependent on genetic predisposition: a rat study

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Russell Vivienne A

2011-05-01

Full Text Available Abstract Background Trauma experienced early in life increases the risk of developing a number of psychological and/or behavioural disorders. It is unclear, however, how genetic predisposition to a behavioural disorder, such as attention-deficit/hyperactivity disorder (ADHD, modifies the long-term effects of early life trauma. There is substantial evidence from family and twin studies for susceptibility to ADHD being inherited, implying a strong genetic component to the disorder. In the present study we used an inbred animal model of ADHD, the spontaneously hypertensive rat (SHR, to investigate the long-term consequences of early life trauma on emotional behaviour in individuals predisposed to developing ADHD-like behaviour. Methods We applied a rodent model of early life trauma, maternal separation, to SHR and Wistar-Kyoto rats (WKY, the normotensive control strain from which SHR were originally derived. The effects of maternal separation (removal of pups from dam for 3 h/day during the first 2 weeks of life on anxiety-like behaviour (elevated-plus maze and depressive-like behaviour (forced swim test were assessed in prepubescent rats (postnatal day 28 and 31. Basal levels of plasma corticosterone were measured using radioimmunoassay. Results The effect of maternal separation on SHR and WKY differed in a number of behavioural measures. Similar to its reported effect in other rat strains, maternal separation increased the anxiety-like behaviour of WKY (decreased open arm entries but not SHR. Maternal separation increased the activity of SHR in the novel environment of the elevated plus-maze, while it decreased that of WKY. Overall, SHR showed a more active response in the elevated plus-maze and forced swim test than WKY, regardless of treatment, and were also found to have higher basal plasma corticosterone compared to WKY. Maternal separation increased basal levels of plasma corticosterone in SHR females only, possibly through adaptive

The Combination of Antidepressant Duloxetine with Piracetam in Mice does not Produce Enhancement of Nootropic Activity

OpenAIRE

Kale, Pravin Popatrao; Addepalli, Veeranjaneyulu; Sarkar, Amrita; Patel, Sonam; Savai, Jay

2014-01-01

There is a strong association between depression and memory impairment. The present study aims to assess the nootropic activity of duloxetine and piracetam combination. Male Swiss Albino mice were divided randomly into 4 groups. Treatment of normal saline (10 ml/kg), duloxetine (10 mg/kg), piracetam (100 mg/kg), and duloxetine (5 mg/kg) plus piracetam (50 mg/kg) were given through intra-peritoneal route to group I-IV, respectively. Transfer latency in elevated plus maze (EPM) and time spent i...

Behavioral phenotyping of mice in pharmacological and toxicological research.

Science.gov (United States)

Karl, Tim; Pabst, Reinhard; von Hörsten, Stephan

2003-07-01

The evaluation of behavioral effects is an important component for the in vivo screening of drugs or potentially toxic compounds in mice. Ideally, such screening should be composed of monitoring general health, sensory functions, and motor abilities, right before specific behavioral domains are tested. A rational strategy in the design and procedure of testing as well as an effective composition of different well-established and reproducible behavioral tests can minimize the risk of false positive and false negative results in drug screening. In the present review we describe such basic considerations in planning experiments, selecting strains of mice, and propose groups of behavioral tasks suitable for a reliable detection of differences in specific behavioral domains in mice. Screening of general health and neurophysiologic functions (reflexes, sensory abilities) and motor function (pole test, wire hang test, beam walking, rotarod, accelerod, and footprint) as well as specific hypothesis-guided testing in the behavioral domains of learning and memory (water maze, radial maze, conditioned fear, and avoidance tasks), emotionality (open field, hole board, elevated plus maze, and object exploration), nociception (tail flick, hot plate), psychiatric-like conditions (porsolt swim test, acoustic startle response, and prepulse inhibition), and aggression (isolation-induced aggression, spontaneous aggression, and territorial aggression) are described in further detail. This review is designed to describe a general approach, which increases reliability of behavioral screening. Furthermore, it provides an overview on a selection of specific procedures suitable for but not limited to behavioral screening in pharmacology and toxicology.

Kv4.2 knockout mice display learning and memory deficits in the Lashley maze [version 1; referees: 2 approved

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Gregory D. Smith

2016-10-01

Full Text Available Background: Potassium channels have been shown to be involved in neural plasticity and learning. Kv4.2 is a subunit of the A-type potassium channel. Kv4.2 channels modulate excitability in the dendrites of pyramidal neurons in the cortex and hippocampus. Deletion of Kv4.2 results in spatial learning and conditioned fear deficits; however, previous studies have only examined deletion of Kv4.2 in aversive learning tests. Methods: For the current study, we used the Lashley maze as an appetitive learning test. We examined Kv4.2 wildtype (WT and knockout (KO mice in the Lashley maze over 4 days during adulthood. The first day consisted of habituating the mice to the maze. The mice then received five trials per day for the next 3 days. The number of errors and the time to the goal box was recorded for each trial. The goal box contained a weigh boat with an appetitive reward (gelatin with sugar. There was an intertrial interval of 15 minutes. Results: We found that Kv4.2 KO mice committed more errors across the trials compared to the WT mice p<0.001. There was no difference in the latency to find the goal box over the period. Discussion: Our finding that deletion of Kv4.2 resulted in more errors in the Lashley maze across 15 trials contribute to a growing body of evidence that Kv4.2 channels are significantly involved in learning and memory.

Kv4.2 knockout mice display learning and memory deficits in the Lashley maze [version 2; referees: 2 approved

Directory of Open Access Journals (Sweden)

Gregory D. Smith

2017-02-01

Full Text Available Background: Potassium channels have been shown to be involved in neural plasticity and learning. Kv4.2 is a subunit of the A-type potassium channel. Kv4.2 channels modulate excitability in the dendrites of pyramidal neurons in the cortex and hippocampus. Deletion of Kv4.2 results in spatial learning and conditioned fear deficits; however, previous studies have only examined deletion of Kv4.2 in aversive learning tests. Methods: For the current study, we used the Lashley maze as an appetitive learning test. We examined Kv4.2 wildtype (WT and knockout (KO mice in the Lashley maze over 4 days during adulthood. The first day consisted of habituating the mice to the maze. The mice then received five trials per day for the next 3 days. The number of errors and the time to the goal box was recorded for each trial. The goal box contained a weigh boat with an appetitive reward (gelatin with sugar. There was an intertrial interval of 15 minutes. Results: We found that Kv4.2 KO mice committed more errors across the trials compared to the WT mice p<0.001. There was no difference in the latency to find the goal box over the period. Discussion: Our finding that deletion of Kv4.2 resulted in more errors in the Lashley maze across 15 trials contribute to a growing body of evidence that Kv4.2 channels are significantly involved in learning and memory.

Shielding of radiation fields generated by {sup 252}Cf in a concrete maze. Part 2 -- Simulation

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Fasso, A.; Ipe, N.E.; Reyna, A. [Stanford Univ., CA (US). Stanford Linear Accelerator Center; McCall, R.C. [McCall Associates, Woodside, CA (US)

1998-03-01

A streaming experiment performed in a concrete maze of shape and size typical of a radiotherapy room was simulated with the Monte Carlo program FLUKA. The purpose of the calculation was to test the performance of the code in the low energy neutron range, and at the same time to provide additional information which could help in optimizing shielding of medical facilities. Instrument responses were calculated at different maze locations for several experimental configurations and were compared with measurements. In addition, neutron and gamma fluence, ambient dose equivalent and effective dose were calculated at the same positions. Both sources used in the experiment, namely a bare {sup 252}Cf source and one shielded by a tungsten shell 5 cm thick, were considered in the simulation.

Do the effects of prenatal exposure and acute treatment of methamphetamine on anxiety vary depending on the animal model used?

Czech Academy of Sciences Publication Activity Database

Šlamberová, R.; Pometlová, M.; Macúchová, E.; Nohejlová, K.; Stuchlík, Aleš; Valeš, Karel

2015-01-01

Roč. 292, Oct 1 (2015), s. 361-369 ISSN 0166-4328 Grant - others:GA ČR(CZ) GA14-03708S; GA MZd(CZ) NT14484 Institutional support: RVO:67985823 Keywords : drug abuse * prenatal exposure * methamphetamine * anxiety * elevated plus-maze * social interaction text * ultrasound vocalization Subject RIV: FH - Neurology Impact factor: 3.002, year: 2015

Younger apes and human children plan their moves in a maze task.

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Völter, Christoph J; Call, Josep

2014-02-01

Planning defined as the predetermination of a sequence of actions towards some goal is crucial for complex problem solving. To shed light on the evolution of executive functions, we investigated the ontogenetic and phylogenetic origins of planning. Therefore, we presented all four great apes species (N=12) as well as 4- and 5-year-old human preschoolers (N=24) with a vertical maze task. To gain a reward placed on the uppermost level of the maze, subjects had to move the reward to the bottom through open gaps situated at each level of the maze. In total, there were ten gaps located over three of the maze's levels, and free passage through these gaps could be flexibly blocked using multiple traps. Due to the decision tree design of the maze, the subjects had to plan their actions depending on the trap configuration up to two steps ahead to successfully retrieve the reward. We found that (1) our measure of planning was negatively correlated with age in nonhuman apes, (2) younger apes as well as 5-year-old children planned their moves up to two steps ahead whereas 4-year-olds were limited to plan one step ahead, and (3) similar performance but different underlying limitations between apes and children. Namely, while all species of nonhuman apes were limited by a lack of motor control, human children exhibited a shortage in shifting their attention across a sequence of subgoals. Copyright © 2013 Elsevier B.V. All rights reserved.

Virus-mediated shRNA knockdown of prodynorphin in the rat nucleus accumbens attenuates depression-like behavior and cocaine locomotor sensitization.

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Cohen, Ami; Whitfield, Timothy W; Kreifeldt, Max; Koebel, Pascale; Kieffer, Brigitte L; Contet, Candice; George, Olivier; Koob, George F

2014-01-01

Dynorphins, endogenous opioid peptides that arise from the precursor protein prodynorphin (Pdyn), are hypothesized to be involved in the regulation of mood states and the neuroplasticity associated with addiction. The current study tested the hypothesis that dynorphin in the nucleus accumbens (NAcc) mediates such effects. More specifically, we examined whether knockdown of Pdyn within the NAcc in rats would alter the expression of depressive-like and anxiety-like behavior, as well as cocaine locomotor sensitization. Wistar rats were injected with adeno-associated viral (AAV) vectors encoding either a Pdyn-specific short hairpin RNA (AAV-shPdyn) or a scrambled shRNA (AAV-shScr) as control. Four weeks later, rats were tested for anxiety-like behavior in the elevated plus maze test and depressive-like behavior in the forced swim test (FST). Finally, rats received one daily injection of saline or cocaine (20 mg/kg, i.p.), followed by assessment of locomotion for 4 consecutive days. Following 3 days of abstinence, the rats completed 2 additional daily cocaine/saline locomotor trials. Pdyn knockdown in the NAcc led to a significant reduction in depressive-like behavior in the FST, but had no effect on anxiety-like behavior in the elevated plus maze. Pdyn knockdown did not alter baseline locomotor behavior, the locomotor response to acute cocaine, or the initial sensitization of the locomotor response to cocaine over the first 4 cocaine treatment days. However, following 3 days abstinence the locomotor response to the cocaine challenge returned to their original levels in the AAV-shPdyn rats while remaining heightened in the AAV-shScr rats. These results suggest that dynorphin in a very specific area of the nucleus accumbens contributes to depressive-like states and may be involved in neuroadaptations in the NAcc that contribute to the development of cocaine addiction as a persistent and lasting condition.

Unique behavioral characteristics and microRNA signatures in a drug resistant epilepsy model.

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Jangsup Moon

Full Text Available BACKGROUND: Pharmacoresistance is a major issue in the treatment of epilepsy. However, the mechanism underlying pharmacoresistance to antiepileptic drugs (AEDs is still unclear, and few animal models have been established for studying drug resistant epilepsy (DRE. In our study, spontaneous recurrent seizures (SRSs were investigated by video-EEG monitoring during the entire procedure. METHODS/PRINCIPAL FINDINGS: In the mouse pilocarpine-induced epilepsy model, we administered levetiracetam (LEV and valproate (VPA in sequence. AED-responsive and AED-resistant mice were naturally selected after 7-day treatment of LEV and VPA. Behavioral tests (open field, object exploration, elevated plus maze, and light-dark transition test and a microRNA microarray test were performed. Among the 37 epileptic mice with SRS, 23 showed significantly fewer SRSs during administration of LEV (n = 16, LEV sensitive (LS group or VPA (n = 7, LEV resistant/VPA sensitive (LRVS group, while 7 epileptic mice did not show any amelioration with either of the AEDs (n = 7, multidrug resistant (MDR group. On the behavioral assessment, MDR mice displayed distinctive behaviors in the object exploration and elevated plus maze tests, which were not observed in the LS group. Expression of miRNA was altered in LS and MDR groups, and we identified 4 miRNAs (miR-206, miR-374, miR-468, and miR-142-5p, which were differently modulated in the MDR group versus both control and LS groups. CONCLUSION: This is the first study to identify a pharmacoresistant subgroup, resistant to 2 AEDs, in the pilocarpine-induced epilepsy model. We hypothesize that modulation of the identified miRNAs may play a key role in developing pharmacoresistance and behavioral alterations in the MDR group.

Responsiveness of the hypothalamic-pituitary-adrenal axis to different novel environments is a consistent individual trait in adult male outbred rats.

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Márquez, Cristina; Nadal, Roser; Armario, Antonio

2005-02-01

Susceptibility to some stress-induced pathologies may be strongly related to individual differences in the responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis to stressors. However, there have been few attempts in rodents to study the reliability of the individual differences in the responsiveness of the HPA to stressors and the relationship to resting corticosterone levels. In the present work, we used a normal population of Sprague-Dawley rats, with a within-subject design. Our objectives were to study: (a) the reliability of the ACTH and corticosterone response to three different novel environments widely used in psychopharmacology and (b) the relationship between stress levels of HPA hormones and the daily pattern of corticosterone secretion (six samples over a 24-h-period). Animals were repeatedly sampled using tail-nick procedure. The novel environments were the elevated plus-maze, the hole-board and the circular corridor. Animals were sampled just after 15 min exposure to the tests and again at 15 and 30 min after the termination of exposure to them (post-tests). The hormonal levels just after the tests indicate that the hole-board seems to be more stressful than the circular corridor and the elevated plus-maze, the latter being characterized by the lowest defecation rate. Correlational analysis revealed that daily pattern of resting plasma corticosterone levels did not correlate to HPA responsiveness to the tests, suggesting no relationship between resting and stress levels of HPA hormones. In contrast, the present study demonstrates, for the first time, a good within-subject reliability of the ACTH and corticosterone responses to the three environments, suggesting that HPA responsiveness to these kind of stressors is a consistent individual trait in adult rats, despite differences in the physical characteristics of the novel environments.

Pregnanolone glutamate, a novel use-dependent NMDA receptor inhibitor, exerts antidepressant-like properties in animal models.

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Karel eVales

2014-04-01

Full Text Available A number of studies demonstrated a rapid onset of an antidepressant effect of non-competitive NMDA receptor antagonists. Nonetheless, its therapeutic potential is rather limited, due to a high coincidence of negative side-effects. Therefore, the challenge seems to be in the development of NMDA receptor (NMDAR antagonists displaying antidepressant properties, and at the same time maintaining regular physiological function of the NMDAR. Previous results demonstrated that naturally occurring neurosteroid 3α5β-pregnanolone sulfate shows pronounced inhibitory action by a use-dependent mechanism on the tonically active NMDAR. The aim of the present experiments is to find out whether the treatment with pregnanolone 3αC derivatives affects behavioral response to chronic and acute stress in an animal model of depression. Adult male mice were used throughout the study. Repeated social defeat and forced swimming tests were used as animal models of depression. The effect of the drugs on the locomotor/exploratory activity in the open-field test was also tested together with an effect on anxiety in the elevated plus maze. Results showed that pregnanolone glutamate (PG did not induce hyperlocomotion, whereas both dizocilpine and ketamine significantly increased spontaneous locomotor activity in the open field. In the elevated plus maze PG displayed anxiolytic-like properties. In forced swimming PG prolonged time to the first floating. Acute treatment of PG disinhibited suppressed locomotor activity in the repeatedly defeated group-housed mice. Aggressive behavior of isolated mice was reduced after the chronic 30-day administration of PG. PG showed antidepressant-like and anxiolytic-like properties in the used tests, with minimal side-effects. Since PG combines GABAA receptor potentiation and use-dependent NMDAR inhibition, synthetic derivatives of neuroactive steroids present a promising strategy for the treatment of mood disorders.

Virus-mediated shRNA knockdown of prodynorphin in the rat nucleus accumbens attenuates depression-like behavior and cocaine locomotor sensitization.

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Ami Cohen

Full Text Available Dynorphins, endogenous opioid peptides that arise from the precursor protein prodynorphin (Pdyn, are hypothesized to be involved in the regulation of mood states and the neuroplasticity associated with addiction. The current study tested the hypothesis that dynorphin in the nucleus accumbens (NAcc mediates such effects. More specifically, we examined whether knockdown of Pdyn within the NAcc in rats would alter the expression of depressive-like and anxiety-like behavior, as well as cocaine locomotor sensitization. Wistar rats were injected with adeno-associated viral (AAV vectors encoding either a Pdyn-specific short hairpin RNA (AAV-shPdyn or a scrambled shRNA (AAV-shScr as control. Four weeks later, rats were tested for anxiety-like behavior in the elevated plus maze test and depressive-like behavior in the forced swim test (FST. Finally, rats received one daily injection of saline or cocaine (20 mg/kg, i.p., followed by assessment of locomotion for 4 consecutive days. Following 3 days of abstinence, the rats completed 2 additional daily cocaine/saline locomotor trials. Pdyn knockdown in the NAcc led to a significant reduction in depressive-like behavior in the FST, but had no effect on anxiety-like behavior in the elevated plus maze. Pdyn knockdown did not alter baseline locomotor behavior, the locomotor response to acute cocaine, or the initial sensitization of the locomotor response to cocaine over the first 4 cocaine treatment days. However, following 3 days abstinence the locomotor response to the cocaine challenge returned to their original levels in the AAV-shPdyn rats while remaining heightened in the AAV-shScr rats. These results suggest that dynorphin in a very specific area of the nucleus accumbens contributes to depressive-like states and may be involved in neuroadaptations in the NAcc that contribute to the development of cocaine addiction as a persistent and lasting condition.

Repeated Acute Oral Exposure to Cannabis sativa Impaired Neurocognitive Behaviours and Cortico-hippocampal Architectonics in Wistar Rats.

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Imam, A; Ajao, M S; Akinola, O B; Ajibola, M I; Ibrahim, A; Amin, A; Abdulmajeed, W I; Lawal, Z A; Ali-Oluwafuyi, A

2017-03-06

The most abused illicit drug in both the developing and the developed world is Cannabis disposing users to varying forms of personality disorders. However, the effects of cannabis on cortico-hippocampal architecture and cognitive behaviours still remain elusive.  The present study investigated the neuro-cognitive implications of oral cannabis use in rats. Eighteen adult Wistar rats were randomly grouped to three. Saline was administered to the control rats, cannabis (20 mg/kg) to the experimental group I, while Scopolamine (1 mg/kg. ip) was administered to the last group as a standard measure for the cannabis induced cognitive impairment. All treatments lasted for seven consecutive days. Open Field Test (OFT) was used to assess locomotor activities, Elevated Plus Maze (EPM) for anxiety-like behaviour, and Y maze paradigm for spatial memory and data subjected to ANOVA and T test respectively. Thereafter, rats were sacrificed and brains removed for histopathological studies. Cannabis significantly reduced rearing frequencies in the OFT and EPM, and increased freezing period in the OFT. It also reduced percentage alternation similar to scopolamine in the Y maze, and these effects were coupled with alterations in the cortico-hippocampal neuronal architectures. These results point to the detrimental impacts of cannabis on cortico-hippocampal neuronal architecture and morphology, and consequently cognitive deficits.

Behavioural analysis of four mouse strains in an anxiety test battery.

Science.gov (United States)

van Gaalen, M M; Steckler, T

2000-10-01

Differences in locomotor activity, exploratory activity and anxiety-like behaviour of C57BL/6ChR,C57BL/6J, Swiss Webster/J and A/J strain were investigated in an anxiety battery. The battery consisted of paradigms studying spontaneous behaviour after a mild stressor, tasks of innate anxiety (light-dark box, elevated plus maze, novel object exploration), response to a conflict situation (Vogel conflict), conditioned fear and response to inescapable swim stress. Locomotor activity was studied in an open field and compared with locomotion in the other tests. Exploratory behaviour was studied in a 16-hole board task. The data confirm previous studies suggesting that A/J mice are a relatively anxious strain. Also, the data indicated that locomotor activity was independent of the paradigm employed, while the rank order of strain-dependent effects on anxiety-related behaviour changed as a function of the task under study. Our data provide further support for the notion that choice of strain is essential in studies of anxiety-related behaviour. Influence of strain should be considered in pharmacological and lesion studies, as well as in studies with mutant mice. In addition, the data indicate that different anxiety paradigms tax different aspects of anxiety, suggesting that a battery of different tests should be used in studies of anxiety-related behaviour.

A novel technique to optimise the length of a linear accelerator treatment room maze without compromising radiation protection.

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Al-Affan, I A M; Evans, S C; Qutub, M; Hugtenburg, R P

2018-03-01

Simulations with the FLUktuierende KAskade (FLUKA) Monte Carlo code were used to establish the possibility of introducing lead to cover the existing concrete walls of a linear accelerator treatment room maze, in order to reduce the dose of the scattered photons at the maze entrance. In the present work, a pilot study performed at Singleton Hospital in Swansea was used to pioneer the use of lead sheets of various thicknesses to absorb scattered low energy photons in the maze. The dose reduction was considered to be due to the strong effect of the photoelectric interaction in lead resulting in attenuation of the back-scattered photons. Calculations using FLUKA with mono-energetic photons were used to represent the main components of the x-ray spectrum up to 10 MV. Mono-energetic photons were used to enable the study of the behaviour of each energy component from the associated interaction processes. The results showed that adding lead of 1 to 4 mm thickness to the walls and floor of the maze reduced the dose at the maze entrance by up to 80%. Subsequent scatter dose measurements performed at the maze entrance of an existing treatment room with lead sheet of 1.3 mm thickness added to the maze walls and floor supported the results from the simulations. The dose reduction at the maze entrance with the lead in place was up to 50%. The variation between simulation and measurement was attributed to the fact that insufficient lead was available to completely cover the maze walls and floor. This novel proposal of partly, or entirely, covering the maze walls with lead a few millimetres in thickness has implications for the design of linear accelerator treatment rooms since it has the potential to provide savings, in terms of space and costs, when an existing maze requires upgrading in an environment where space is limited and the maze length cannot be extended sufficiently to reduce the dose.

Neural hyperactivity in the amygdala induced by chronic treatment of rats with analgesics may elucidate the mechanisms underlying psychiatric comorbidities associated with medication-overuse headache.

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Wanasuntronwong, Aree; Jansri, Ukkrit; Srikiatkhachorn, Anan

2017-01-03

Patients with medication-overuse headache suffer not only from chronic headache, but often from psychiatric comorbidities, such as anxiety and depression. The mechanisms underlying these comorbidities are unclear, but the amygdala is likely to be involved in their pathogenesis. To investigate the mechanisms underlying the comorbidities we used elevated plus maze and open field tests to assess anxiety-like behavior in rats chronically treated with analgesics. We measured the electrical properties of neurons in the amygdala, and examined the cortical spreading depression (CSD)-evoked expression of Fos in the trigeminal nucleus caudalis (TNC) and amygdala of rats chronically treated with analgesics. CSD, an analog of aura, evokes Fos expression in the TNC of rodents suggesting trigeminal nociception, considered to be a model of migraine. Increased anxiety-like behavior was seen both in elevated plus maze and open field tests in a model of medication overuse produced in male rats by chronic treatment with aspirin or acetaminophen. The time spent in the open arms of the maze by aspirin- or acetaminophen-treated rats (53 ± 36.1 and 37 ± 29.5 s, respectively) was significantly shorter than that spent by saline-treated vehicle control rats (138 ± 22.6 s, P amygdala as indicated by their more negative threshold for action potential generation (-54.6 ± 5.01 mV for aspirin-treated, -55.2 ± 0.97 mV for acetaminophen-treated, and -31.50 ± 5.34 mV for saline-treated rats, P amygdala [18 ± 10.2 Fos-immunoreactive (IR) neurons per slide in the amygdala of rats treated with aspirin, 11 ± 5.4 IR neurons per slide in rats treated with acetaminophen, and 4 ± 3.7 IR neurons per slide in saline-treated control rats, P amygdala, which could underlie the anxiety seen in patients with medication-overuse headache.

Agomelatine, venlafaxine, and running exercise effectively prevent anxiety- and depression-like behaviors and memory impairment in restraint stressed rats.

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Sarawut Lapmanee

Full Text Available Several severe stressful situations, e.g., natural disaster, infectious disease out break, and mass casualty, are known to cause anxiety, depression and cognitive impairment, and preventive intervention for these stress complications is worth exploring. We have previously reported that the serotonin-norepinephrine-dopamine reuptake inhibitor, venlafaxine, as well as voluntary wheel running are effective in the treatment of anxiety- and depression-like behaviors in stressed rats. But whether they are able to prevent deleterious consequences of restraint stress in rats, such as anxiety/depression-like behaviors and memory impairment that occur afterward, was not known. Herein, male Wistar rats were pre-treated for 4 weeks with anti-anxiety/anti-depressive drugs, agomelatine and venlafaxine, or voluntary wheel running, followed by 4 weeks of restraint-induced stress. During the stress period, rats received neither drug nor exercise intervention. Our results showed that restraint stress induced mixed anxiety- and depression-like behaviors, and memory impairment as determined by elevated plus-maze, elevated T-maze, open field test (OFT, forced swimming test (FST, and Morris water maze (MWM. Both pharmacological pre-treatments and running successfully prevented the anxiety-like behavior, especially learned fear, in stressed rats. MWM test suggested that agomelatine, venlafaxine, and running could prevent stress-induced memory impairment, but only pharmacological treatments led to better novel object recognition behavior and positive outcome in FST. Moreover, western blot analysis demonstrated that venlafaxine and running exercise upregulated brain-derived neurotrophic factor (BDNF expression in the hippocampus. In conclusion, agomelatine, venlafaxine as well as voluntary wheel running had beneficial effects, i.e., preventing the restraint stress-induced anxiety/depression-like behaviors and memory impairment.

[The battery of tests for behavioral phenotyping of aging animals in the experiment].

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Gorina, Ya V; Komleva, Yu K; Lopatina, O L; Volkova, V V; Chernykh, A I; Shabalova, A A; Semenchukov, A A; Olovyannikova, R Ya; Salmina, A B

2017-01-01

The purpose of the study was to develop a battery of tests to study social and cognitive impairments for behavioral phenotyping of aging experimental animals with physiological neurodegeneration. Object of the study were outbred CD1 mice in the following groups: 1st group - 12-month old male mice (physiological aging); 2nd group - 2-month old male mice (control group). Social recognition test, elevated plus maze test (EPM), open field test, light-dark box test, and Fear conditioning protocol were used to estimate the neurological status of experimental animals. We found that aging male mice in a contrast to young ones have demonstrated lower social interest to female mice in the social recognition task. EPM and light-dark box tests showed increased level of anxiety in the group of aged mice comparing to the control group. Fear conditioning protocol revealed impairment of associative learning and memory in the group of aged mice, particularly, fear memory consolidation was dramatically suppressed. Analysis of behavioral factors, social interactions and anxiety level in the experimental mice has confirmed age-related neurodegeneration in the 1st group. We found that the most informative approach to identifying neurological impairments in aging mice (social interaction deficit, limitation of interests, increased level of anxiety) should be based on the open field test light-dark box test, and Fear conditioning protocol. Such combination allows obtaining new data on behavioral alterations in the age-associated of neurodegeneration and to develop novel therapeutic strategies for the treatment of age-related brain pathology.

Comprehensive behavioral analysis of mice deficient in Rapgef2 and Rapgef6, a subfamily of guanine nucleotide exchange factors for Rap small GTPases possessing the Ras/Rap-associating domain.

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Maeta, Kazuhiro; Hattori, Satoko; Ikutomo, Junji; Edamatsu, Hironori; Bilasy, Shymaa E; Miyakawa, Tsuyoshi; Kataoka, Tohru

2018-05-10

Rapgef2 and Rapgef6 define a subfamily of guanine nucleotide exchange factors for Rap small GTPases, characterized by the possession of the Ras/Rap-associating domain. Previous genomic analyses suggested their possible involvement in the etiology of schizophrenia. We recently demonstrated the development of an ectopic cortical mass (ECM), which resembles the human subcortical band heterotopia, in the dorsal telencephalon-specific Rapgef2 conditional knockout (Rapgef2-cKO) brains. Additional knockout of Rapgef6 in Rapgef2-cKO mice resulted in gross enlargement of the ECM whereas knockout of Rapgef6 alone (Rapgef6-KO) had no discernible effect on the brain morphology. Here, we performed a battery of behavioral tests to examine the effects of Rapgef2 or Rapgef6 deficiency on higher brain functions. Rapgef2-cKO mice exhibited hyperlocomotion phenotypes. They showed decreased anxiety-like behavior in the elevated plus maze and the open-field tests as well as increased depression-like behavior in the Porsolt forced swim and tail suspension tests. They also exhibited increased sociability especially in novel environments. They showed defects in cognitive function as evidenced by reduced learning ability in the Barnes circular maze test and by impaired working memory in the T maze tests. In contrast, although Rapgef6 and Rapgef2 share similarities in biochemical roles, Rapgef6-KO mice exhibited mild behavioral abnormalities detected with a number of behavioral tests, such as hyperlocomotion phenotype in the open-field test and the social interaction test with a novel environment and working-memory defects in the T-maze test. In conclusion, although there were differences in their brain morphology and the magnitude of the behavioral abnormalities, Rapgef2-cKO mice and Rapgef6-KO mice exhibited hyperlocomotion phenotype and working-memory defect, both of which could be recognized as schizophrenia-like behavior.

The Neuron-Specific Protein TMEM59L Mediates Oxidative Stress-Induced Cell Death.

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Zheng, Qiuyang; Zheng, Xiaoyuan; Zhang, Lishan; Luo, Hong; Qian, Lingzhi; Fu, Xing; Liu, Yiqian; Gao, Yuehong; Niu, Mengxi; Meng, Jian; Zhang, Muxian; Bu, Guojun; Xu, Huaxi; Zhang, Yun-Wu

2017-08-01

TMEM59L is a newly identified brain-specific membrane-anchored protein with unknown functions. Herein we found that both TMEM59L and its homolog, TMEM59, are localized in Golgi and endosomes. However, in contrast to a ubiquitous and relatively stable temporal expression of TMEM59, TMEM59L expression was limited in neurons and increased during development. We also found that both TMEM59L and TMEM59 interacted with ATG5 and ATG16L1, and that overexpression of them triggered cell autophagy. However, overexpression of TMEM59L induced intrinsic caspase-dependent apoptosis more dramatically than TMEM59. In addition, downregulation of TMEM59L prevented neuronal cell death and caspase-3 activation caused by hydrogen peroxide insults and reduced the lipidation of LC3B. Finally, we found that AAV-mediated knockdown of TMEM59L in mice significantly ameliorated caspase-3 activation, increased mouse duration in the open arm during elevated plus maze test, reduced mouse immobility time during forced swim test, and enhanced mouse memory during Y-maze and Morris water maze tests. Together, our study indicates that TMEM59L is a pro-apoptotic neuronal protein involved in animal behaviors such as anxiety, depression, and memory, and that TMEM59L downregulation protects neurons against oxidative stress.

Evidence-based severity assessment: Impact of repeated versus single open-field testing on welfare in C57BL/6J mice.

Science.gov (United States)

Bodden, Carina; Siestrup, Sophie; Palme, Rupert; Kaiser, Sylvia; Sachser, Norbert; Richter, S Helene

2018-01-15

According to current guidelines on animal experiments, a prospective assessment of the severity of each procedure is mandatory. However, so far, the classification of procedures into different severity categories mainly relies on theoretic considerations, since it is not entirely clear which of the various procedures compromise the welfare of animals, or, to what extent. Against this background, a systematic empirical investigation of the impact of each procedure, including behavioral testing, seems essential. Therefore, the present study was designed to elucidate the effects of repeated versus single testing on mouse welfare, using one of the most commonly used paradigms for behavioral phenotyping in behavioral neuroscience, the open-field test. In an independent groups design, laboratory mice (Mus musculus f. domestica) experienced either repeated, single, or no open-field testing - procedures that are assigned to different severity categories. Interestingly, testing experiences did not affect fecal corticosterone metabolites, body weights, elevated plus-maze or home cage behavior differentially. Thus, with respect to the assessed endocrinological, physical, and behavioral outcome measures, no signs of compromised welfare could be detected in mice that were tested in the open-field repeatedly, once, or, not at all. These findings challenge current classification guidelines and may, furthermore, stimulate systematic research on the severity of single procedures involving living animals. Copyright © 2017 Elsevier B.V. All rights reserved.

Improving Students’ English Pronunciation Ability Through Go Fish Game and Maze Game

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Dwi Astuti Wahyu Nurhayati

2015-12-01

Full Text Available The problem highlighted in this research is the low pronunciation ability of Kindergarten students in Al-Irsyad  Madiun  that is caused by (1 the uninteresting activities in learning English; (2 the students' difficulties in pronunciating English words; (3 the students' low motivation in learning. The theoretical review includes the young learners characteristics, games in language, games for young learners. The procedure of the research consists of identifying the problem, planning the action, implementing the action, observing the action, and reflecting the result of the research. In this research, the researcher acts as the teacher who conducts the action research in the classroom and she is helped by the classsroom teacher. In collecting the data, the researcher uses observational technique supported with tests. In analyzing the data, the researcher uses the field notes, teacher's diaries, students ‘work supported with the cassette recording and photograph,then also compares the result of the students' pre-test and post-test to answer the research questions. There is significant improvement in the result of pre-test and post-test of cycle 1 and 2. In cycle 1, t0 (2.55734 is higher than tt (1.73 and in cycle 2, t0 (6.765738 is also higher than tt (1.73. From these two results, therefore, h0 is rejected and the alternative hypothesis (ha is accepted. They practice their pronunciation through taking turn and asking each other for cards to match those they have in their hands, arranging a word and sticking on alphabet, pronunciating the word, giving the meaning, hen making a sentence such as Go Fish Game and Maze Game. By conducting these games, using interesting media, creating various interesting tasks and activities can increase the students' motivation in learning English and pronunciation ability.Keywords: Improving, pronunciation, ability,  go fish and Maze games

Use of an Eight-arm Radial Water Maze to Assess Working and Reference Memory Following Neonatal Brain Injury

OpenAIRE

Penley, Stephanie C.; Gaudet, Cynthia M.; Threlkeld, Steven W.

2013-01-01

Working and reference memory are commonly assessed using the land based radial arm maze. However, this paradigm requires pretraining, food deprivation, and may introduce scent cue confounds. The eight-arm radial water maze is designed to evaluate reference and working memory performance simultaneously by requiring subjects to use extra-maze cues to locate escape platforms and remedies the limitations observed in land based radial arm maze designs. Specifically, subjects are required to avoid ...

The effect of Resveratrol flavonoid on learning and memory in passive avoidance and Y maze in diabetic rat

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Sima Nasri

2014-04-01

Full Text Available Background: Diabetes type I is accompanied with disturbances in cognitive skills, memory and learning. In this research, we evaluated the effect of resveratrol chronic treatment on learning and memory in diabetic male rats. Material and Methods: Rats were divided into 4 groups: control, resveratrol-treated control, diabetic and resveratrol-treated diabetic groups. We used streptozotosin for inducing diabetes. Resveratrol (10mg/kg I.p. was administered for 8 weeks. For evaluation of learning and memory, passive avoidance test and Y-maze task were used. For Statistical analysis, SPSS software and paired T-test and one-way ANOVA were used. Results: Resveratrol decreased serum glucose in diabetic rats (P<0.01. In passive avoidance learning, there wasn’t any significant difference in initial latency between diabetic and treated- diabetic group. Also, a significant decrease of step latency was observed in diabetic and treated diabetic rats (P<0.01. In Y maze, Resveratrol improved alternation percentage in diabetic rats. Conclusion: Probably due to different mechanism of long term and short term memory, long term resveratrol treatment didn’t improve memory and learning in passive avoidance learning. In Y maze, method for determining the spatial memory, resveratrol improved spatial memory in diabetic rats. Resveratrol not only regulates glucose in diabetic rats but also it improves short term memory.

CBM maze-scores as indicators of reading level and growth for seventh-grade students

NARCIS (Netherlands)

Chung, S.; Espin, C.A.; Stevenson, C.E.

The technical adequacy of CBM maze-scores as indicators of reading level and growth for seventh-grade secondary-school students was examined. Participants were 452 Dutch students who completed weekly maze measures over a period of 23 weeks. Criterion measures were school level, dyslexia status,

Anti-anxiety and anti-depressant like effects of murraya koenigii in experimental models of anxiety and depression

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Snigdha Sharma

2017-01-01

Full Text Available Background: Presence of free radical scavenging activity in Murraya koenigii, commonly known as Curry leaves, has been shown in previous studies. Oxidative stress plays an important role in the development of various neurobehavioral disorders including anxiety and depression. Aim: The present study aimed to evaluate the effects of Murraya koenigii in animal models of depression and anxiety. Materials and Methods: The effect of incremental doses of Murraya koenigii aqueous leaf extract was evaluated on spontaneous motor activity (SMA, open arm incursions in elevated plus maze, and despair behaviour in forced swim (FST and tail suspension (TST tests as compared to control groups in Swiss albino mice. Results: Murraya koenigii 300 mg/kg, p.o. (MK300 and 400 mg/kg, p.o. (MK400 reduced the SMA count from 754 ± 64.9 to 540 ± 29 and 295 ± 34 respectively, which was statistically significant. MK300 and MK400 reduced significantly the open arm count from 29 ± 8.6 to 16 ± 7 and 10 ± 3.9, respectively. On FST, MK400 reduced the duration of immobility from 145.5 ± 29 to 91 ± 17.3, which was statistically significant. On TST, MK produced a dose-dependent decrease in the duration of immobility; however, it was statistically significant only with MK400. Conclusion: Murraya koenigii aqueous leaf extract reduced the despair behavior in experimental animal models, suggesting an anti-depressant like activity. Murraya koenigii extract also reduced spontaneous locomotor activity in a dose-dependent manner suggesting a sedative and/or anxiolytic effect though there wasn't any anxiolytic effect in the elevated plus maze test.

Trigeminal Inflammatory Compression (TIC) injury induces chronic facial pain and susceptibility to anxiety-related behaviors.

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Lyons, D N; Kniffin, T C; Zhang, L P; Danaher, R J; Miller, C S; Bocanegra, J L; Carlson, C R; Westlund, K N

2015-06-04

Our laboratory previously developed a novel neuropathic and inflammatory facial pain model for mice referred to as the Trigeminal Inflammatory Compression (TIC) model. Rather than inducing whole nerve ischemia and neuronal loss, this injury induces only slight peripheral nerve demyelination triggering long-term mechanical allodynia and cold hypersensitivity on the ipsilateral whisker pad. The aim of the present study is to further characterize the phenotype of the TIC injury model using specific behavioral assays (i.e. light-dark box, open field exploratory activity, and elevated plus maze) to explore pain- and anxiety-like behaviors associated with this model. Our findings determined that the TIC injury produces hypersensitivity 100% of the time after surgery that persists at least 21 weeks post injury (until the animals are euthanized). Three receptive field sensitivity pattern variations in mice with TIC injury are specified. Animals with TIC injury begin displaying anxiety-like behavior in the light-dark box preference and open field exploratory tests at week eight post injury as compared to sham and naïve animals. Panic anxiety-like behavior was shown in the elevated plus maze in mice with TIC injury if the test was preceded with acoustic startle. Thus, in addition to mechanical and cold hypersensitivity, the present study identified significant anxiety-like behaviors in mice with TIC injury resembling the clinical symptomatology and psychosocial impairments of patients with chronic facial pain. Overall, the TIC injury model's chronicity, reproducibility, and reliability in producing pain- and anxiety-like behaviors demonstrate its usefulness as a chronic neuropathic facial pain model. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

The antidepressant- and anxiolytic-like effects following co-treatment with escitalopram and risperidone in rats.

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Kaminska, K; Rogoz, Z

2016-06-01

Several clinical reports have documented a beneficial effect of the addition of a low dose of risperidone to the ongoing treatment with antidepressants, in particular selective serotonin reuptake inhibitors (SSRI), in the treatment of drug-resistant depression and treatment-resistant anxiety disorders. In the present study, we investigated the effect of treatment with the antidepressant escitalopram (SSRI) given separately or jointly with a low dose of risperidone (an atypical antipsychotic) in the forced swim test and in the elevated plus-maze test in rats. The obtained results showed that escitalopram at doses of 2.5 or 5 mg/kg evoked antidepressant-like effect in the forced swim test. Moreover, risperidone at low doses (0.05 or 0.1 mg/kg) enhanced the antidepressant-like activity of escitalopram (1 mg/kg) in this test by increasing the swimming time and decreasing the immobility time in those animals. WAY 100635 (a serotonin 5-HT1A receptor antagonist) at a dose of 0.1 mg/kg abolished the antidepressant-like effect induced by co-administration of escitalopram and risperidone. The active behavior in that test did not reflect an increase in general activity, since the combined treatment with escitalopram and risperidone failed to enhance the exploratory activity of rats. In the following experiment, we showed that escitalopram (5 mg/kg) and mirtazapine (5 or 10 mg/kg) or risperidone (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze test, and the combined treatment with an ineffective dose of risperidone (0.05 mg/kg) enhanced the anxiolytic-like effects of escitalopram (2.5 mg/kg) or mirtazapine (1 and 2.5 mg/kg) in this test. The obtained results suggest that risperidone applied at a low dose enhances the antidepressant-like activity of escitalopram in the forced swim test, and that 5-HT1A receptors may play some role in these effects. Moreover, a low dose of risperidone may also enhance the anxiolytic-like action of the studied

Shake Table Testing of an Elevator System in a Full-Scale Five-Story Building.

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Wang, Xiang; Hutchinson, Tara C; Astroza, Rodrigo; Conte, Joel P; Restrepo, José I; Hoehler, Matthew S; Ribeiro, Waldir

2017-03-01

This paper investigates the seismic performance of a functional traction elevator as part of a full-scale five-story building shake table test program. The test building was subjected to a suite of earthquake input motions of increasing intensity, first while the building was isolated at its base, and subsequently while it was fixed to the shake table platen. In addition, low-amplitude white noise base excitation tests were conducted while the elevator system was placed in three different configurations, namely, by varying the vertical location of its cabin and counterweight, to study the acceleration amplifications of the elevator components due to dynamic excitations. During the earthquake tests, detailed observation of the physical damage and operability of the elevator as well as its measured response are reported. Although the cabin and counterweight sustained large accelerations due to impact during these tests, the use of well-restrained guide shoes demonstrated its effectiveness in preventing the cabin and counterweight from derailment during high-intensity earthquake shaking. However, differential displacements induced by the building imposed undesirable distortion of the elevator components and their surrounding support structure, which caused damage and inoperability of the elevator doors. It is recommended that these aspects be explicitly considered in elevator seismic design.

DEPRESSIVE BEHAVIOR AND METABOLIC ALTERATIONS IN MICE ARE MUSICAL STYLE-DEPENDENT

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V. S. Lima

2015-10-01

Full Text Available Nowadays, the world population has been affected by two serious psychological disorders, anxiety and depression, but there are few discoveries for new therapies to combat them. Studies have shown that music therapy has its beneficial behavioral effects. Therefore, the aim of the present study it was to investigate the possible effects of two music styles in some lipids and carbohydrate metabolism parameters resulting from behavioral changes related to anxiety and depression. So, mice were used with 30 days of age, divided into 6 groups: G1: saline, G2: Diazepam (DZP, G3: Fluoxetine (FLX, G4: control (no treatment, G5: Rock, and G6: Mozart Sonata. The animals from groups G1, G2 and G3 received treatments by oral route (gavage for 15 days. The music therapy sessions (2x/day 4 hours/day occurred in the same period of time at a 65dB frequency for G5 and G6 groups. After being evaluated in spontaneous locomotion, elevated plus maze and forced swimming tests, the animals were euthanized. The lactate, total cholesterol and plasma glucose levels were measured from the blood. No change was observed in spontaneous locomotion test and elevated plus maze. In the forced swimming test animals exposed to Rock showed an increase in immobility time. Furthermore, it was observed an increase in glucose and a reduction in cholesterol levels in the groups exposed to Rock and Mozart, while a decrease of lactate was observed only in group Rock. It was concluded that the auditory stimulus caused by music in mice was able to encourage depressive behavior and alter some lipids and carbohydrate metabolism parameters dependently of the musical style.

Adolescent exposure to Bisphenol-A increases anxiety and sucrose preference but impairs spatial memory in rats independent of sex.

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Diaz Weinstein, Samantha; Villafane, Joseph J; Juliano, Nicole; Bowman, Rachel E

2013-09-05

The endocrine disruptor Bisphenol-A (BPA) has been shown to modulate estrogenic, androgenic, and anti-androgenic effects. The effects of BPA exposure during early organizational periods of development have been well documented. The current study focuses on the effects of short term, low-dose BPA exposure on anxiety, spatial memory and sucrose preference in adolescent rats. Seven week old Sprague Dawley rats (n=18 male, n=18 female) received daily subcutaneous injections (40 µg/kg body weight) of BPA or vehicle for 12 days. Starting on day 6 of injections, subjects were tested on the elevated plus maze which provides a measure of anxiety, the open field test which provides a measure of anxiety and locomotor activity, and object placement, a measure of spatial memory. On the twelfth day of BPA administration, sucrose preference was tested using a standard two-bottle choice (tap versus sucrose solution). All rats gained weight during the study; there was a main effect of sex, but not BPA treatment on body weight. The results indicate that BPA exposure, regardless of sex, increased anxiety on both the elevated plus maze and open field. Spatial memory was impaired on the object recognition task with BPA animals spending significant less time with the object in the novel location than controls. Finally, a significant increase in sucrose consumption for both male and female subjects exposed to BPA was observed. The current data shows that short term BPA exposure, below the current reference safe daily limit of 50 µg/kg day set by the United States Environmental Protection Agency, during adolescent development increases anxiety, impairs spatial memory, and increases sucrose consumption independent of sex. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of an early experience involving training in a T-maze under either denial or receipt of expected reward through maternal contact.

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Antonios eStamatakis

2013-11-01

Full Text Available The mother is the most salient stimulus for the developing pups and a number of early experience models employ manipulation of the mother-infant interaction. We have developed a new model which in addition to changes in maternal behavior includes a learning component on the part of the pups. More specifically, pups were trained in a T-maze and either received (RER rats or were denied (DER the reward of maternal contact, during postnatal days 10—13.Pups of both experimental groups learn the T-maze, but the RER do so more efficiently utilizing a procedural-type of learning and memory with activation of the dorsal basal ganglia. On the other hand, the DER experience leads to activation of the hippocampus, prefrontal cortex and amygdala in the pups.In adulthood, male DER animals exhibit better mnemonic abilities in the Morris water maze and higher activation of the hippocampus, while they have decreased brain serotonergic activity, exhibit a depressive-like phenotype and proactive aggressive behavior in the resident-intruder test. On the other hand, male RER animals assume a reactive coping style in this test, showed increased emotionality as well as freezing in the memory test following both contextual and cued fear conditioning.

The Canine Sand Maze: An Appetitive Spatial Memory Paradigm Sensitive to Age-Related Change in Dogs

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Salvin, Hannah E.; McGreevy, Paul D.; Sachdev, Perminder S.; Valenzuela, Michael J.

2011-01-01

Aged dogs exhibit a spectrum of cognitive abilities including a syndrome similar to Alzheimer's disease. A major impediment to research so far has been the lack of a quick and accurate test of visuospatial memory appropriate for community-based animals. We therefore report on the development and validation of the Canine Sand Maze. A 4.5-m-diameter…

Selective impairment of subcategories of long-term memory in mice with hippocampal lesions accessed by the olfactory tubing maze.

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Chaillan, F A; Marchetti, E; Soumireu-Mourat, B; Roman, F S

2005-03-30

A new apparatus, the olfactory tubing maze for mice, was developed recently to study learning and memory processes in mice in regard to their ethological abilities. As in humans, BALB/c mice with selective bilateral lesions of the hippocampal formation showed selective impairment of subcategories of long-term memory when tested with the olfactory tubing maze. After three learning sessions, control mice reached a high percentage of correct responses. They consistently made the olfactory-reward associations, but antero-dorsal and postero-ventral hippocampal-lesioned mice did not. However, all lesioned mice learned the paradigm and the timing of the task as fast and as well as control mice. These data suggest that the olfactory tubing maze can be used to study subcategories of memory, such as declarative and non-declarative memory, which are similar in some respects to those observed in humans. Consequently, possible memory effects of classical approaches (i.e., pharmacological or lesion studies) or genetic modifications in transgenic or gene-targeting mice can be effectively analyzed using this new apparatus.

Correlation between the concentration of serum polychlorinated biphenyls (PCBs) in pregnant cynomolgus monkeys and their offspring's behavioral scores in eye-contact test and finger maze learning test

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Negishi, T. [Aoyama Gakuin Univ., Kanagawa (Japan); Takasuga, T. [Shimadzu Techno-Research Inc., Kyoto (Japan); Kawasaki, K. [Hoshi Univ., Tokyo (Japan); Kuroda, Y. [CREST Japan Science and Technology Corp., Saitama (Japan); Yoshikawa, Y. [The Univ. of Tokyo (Japan)

2004-09-15

A recent review suggested that pre- or perinatal exposure of developing fetuses to dioxins, the widespread environmental contaminants, such as polychrorinated biphenlys (PCBs), induce the irreversible abnormalities in the functions of central nervous system (CNS) in human. These chemicals can be transferred to each fetus and naonate transplacentally and lactationally in rhesus monkey. Several studies also reported the adverse effect of PCB on CNS development in rodents and monkeys as well as on behavior in rodents and monkeys. In the present study, we show a preliminary data about the correlation between the serum concentrations of PCBs in pregnant cynomolgus monkeys (Macaca fascicularis) and the scores of two behavioral tests, eye-contact test and four-step finger maze test, which evaluate consciousness against human observer and learning ability, respectively, in their offspring. This experimental surveillance system using non-human primates would be useful to predict the risk of PCBs exposure in human fetuses because of the similarities of cynomolgus monkey to human with regard to reproduction, developmental parameter, and others.

Synthesis, Anticonvulsant, Sedative and Anxiolytic Activities of Novel Annulated Pyrrolo[1,4]benzodiazepines

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Kumaraswamy Sorra

2014-09-01

Full Text Available Four new pentacyclic benzodiazepine derivatives (PBDTs 13–16 were synthesized by conventional thermal heating and microwave-assisted intramolecular cyclocondensation. Their anticonvulsant, sedative and anxiolytic activities were evaluated by drug-induced convulsion models, a pentobarbital-induced hypnotic model and an elevated plus maze in mice. PBDT 13, a triazolopyrrolo[2,1-c][1,4]benzodiazepin-8-one fused with a thiadiazolone ring, exhibited the best anticonvulsant, sedative and anxiolytic effects in our tests. There was no significant difference in potency between PBDT 13 and diazepam, and we proposed that the action mechanism of PBDT 13 could be similar to that of diazepam via benzodiazepine receptors.

Environmental Enrichment during Gestation Improves Behavior Consequences and Synaptic Plasticity in Hippocampus of Prenatal-Stressed Offspring Rats

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Li, Mingbo; Wang, Miao; Ding, Siqing; Li, Changqi; Luo, Xuegang

2012-01-01

Prenatal stress can result in various behavior deficits in offspring. Here we tested the effects of environmental enrichment during gestation used as a preventive strategy on the behavior deficits of prenatal-stressed offspring rats as well as the underlying structure basis. We compared the effect size of environmental enrichment during gestation on prenatal-stressed offspring to that of environmental enrichment after weaning. Our results showed that environmental enrichment during gestation partially prevented anxiety and the damage in learning and memory in prenatal-stressed offspring as evaluated by elevated plus-maze test and Morris water maze test. At the same time, environmental enrichment during gestation inhibited the decrease in spine density of CA1 and dentate gyrus neurons and preserved the expression of synaptophysin and glucocorticoid receptors (GRs) in the hippocampus of prenatal-stressed offspring. There was no significant difference in offspring behavior between 7-day environmental enrichment during gestation and 14-day offspring environmental enrichment after weaning. These data suggest that environmental enrichment during gestation effectively prevented the behavior deficits and the abnormal synapse structures in prenatal-stressed offspring, and that it can be used as an efficient preventive strategy against prenatal stresses

[Analysis of variance of repeated data measured by water maze with SPSS].

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Qiu, Hong; Jin, Guo-qin; Jin, Ru-feng; Zhao, Wei-kang

2007-01-01

To introduce the method of analyzing repeated data measured by water maze with SPSS 11.0, and offer a reference statistical method to clinical and basic medicine researchers who take the design of repeated measures. Using repeated measures and multivariate analysis of variance (ANOVA) process of the general linear model in SPSS and giving comparison among different groups and different measure time pairwise. Firstly, Mauchly's test of sphericity should be used to judge whether there were relations among the repeatedly measured data. If any (PSPSS statistical package is available to fulfil this process.

Novel development of the micro-tensile test at elevated temperature using a test structure with integrated micro-heater

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Ang, W. C.; Kropelnicki, P.; Soe, Oak; Ling, J. H. L.; Randles, A. B.; Hum, A. J. W.; Tsai, J. M. L.; Tay, A. A. O.; Leong, K. C.; Tan, C. S.

2012-08-01

This paper describes the novel development of a micro-tensile testing method that allows testing at elevated temperatures. Instead of using a furnace, a titanium/platinum thin film micro-heater was fabricated on a conventional dog-bone-shaped test structure to heat up its gauge section locally. An infrared (IR) camera with 5 µm resolution was employed to verify the temperature uniformity across the gauge section of the test structure. With this micro-heater-integrated test structure, micro-tensile tests can be performed at elevated temperatures using any conventional tensile testing system without any major modification to the system. In this study, the tensile test of the single crystal silicon (SCS) thin film with (1 0 0) surface orientation and tensile direction was performed at room temperature and elevated temperatures, up to 300 °C. Experimental results for Young's modulus as a function of temperature are presented. A micro-sized SCS film showed a low dependence of mechanical properties on temperature up to 300 °C.

Sodium selenite supplementation during pregnancy and lactation promotes anxiolysis and improves mnemonic performance in wistar rats' offspring.

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Laureano-Melo, Roberto; Império, Güínever Eustáquio do; da Silva-Almeida, Claudio; Kluck, George Eduardo Gabriel; Cruz Seara, Fernando de Azevedo; da Rocha, Fábio Fagundes; da Silveira, Anderson Luiz Bezerra; Reis, Luís Carlos; Ortiga-Carvalho, Tania Maria; da Silva Côrtes, Wellington

2015-11-01

Selenium is a micronutrient which is part of selenoprotein molecules and participates in a vast number of physiological roles and, among them,we have fetal and neonatal development. Therefore, the aimof this studywas to evaluate possible behavioral changes in offspring of female rats supplemented during pregnancy and lactation with sodium selenite. To address that, we treated two groups of female rats by saline or sodium selenite at a dose of 1mg/kg through oral route and performed neurochemical and behavioral tests. In the offspring, the thyroid profile and hippocampal neurochemistrywere evaluated. Behavioral testswere performed in pups both during childhood and adulthood. We found out that selenium (Se) supplementation increased serum levels of triiodothyronine (25%, p b 0.001) and thyroxine (18%, p b 0.05) and promoted a tryptophan hydroxylase 2 (TPH 2) expression decrease (17%, p b 0.01) and tyrosine hydroxylase (TH) expression increase (202%, p b 0.01) in the hippocampus. The cholinesterase activity was decreased (28%, p b 0.01) in Se supplemented rats, suggesting a neurochemical modulation in the hippocampal activity. During childhood, the Sesupplemented offspring had a reduction in anxiety-like behavior both in elevated plus maze test and in light–dark box test. In adulthood, Se-treated pups had an increase in the locomotor activity (36%, p b 0.05) and in rearing episodes (77%, p b 0.001) in the open field test, while in the elevated plus maze test they also exhibited an increase in the time spent in the open arms (243%, p b 0.01). For the object recognition test, Se-treated offspring showed increase in the absolute (230.16%, p b 0.05) and relative index discrimination (234%, p b 0.05). These results demonstrate that maternal supplementation by sodium selenite promoted psychobiological changes both during childhood and adulthood. Therefore, the behavioral profile observed possibly can be explained by neurochemical changes induced by thyroid hormones during

Chronic and acute adenosine A2A receptor blockade prevents long-term episodic memory disruption caused by acute cannabinoid CB1 receptor activation.

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Mouro, Francisco M; Batalha, Vânia L; Ferreira, Diana G; Coelho, Joana E; Baqi, Younis; Müller, Christa E; Lopes, Luísa V; Ribeiro, Joaquim A; Sebastião, Ana M

2017-05-01

Cannabinoid-mediated memory impairment is a concern in cannabinoid-based therapies. Caffeine exacerbates cannabinoid CB 1 receptor (CB 1 R)-induced memory deficits through an adenosine A 1 receptor-mediated mechanism. We now evaluated how chronic or acute blockade of adenosine A 2A receptors (A 2A Rs) affects long-term episodic memory deficits induced by a single injection of a selective CB 1 R agonist. Long-term episodic memory was assessed by the novel object recognition (NOR) test. Mice received an intraperitoneal (i.p.) injection of the CB 1 /CB 2 receptor agonist WIN 55,212-2 (1 mg/kg) immediately after the NOR training, being tested for novelty recognition 24 h later. Anxiety levels were assessed by the Elevated Plus Maze test, immediately after the NOR. Mice were also tested for exploratory behaviour at the Open Field. For chronic A 2A R blockade, KW-6002 (istradefylline) (3 mg/kg/day) was administered orally for 30 days; acute blockade of A 2A Rs was assessed by i.p. injection of SCH 58261 (1 mg/kg) administered either together with WIN 55,212-2 or only 30 min before the NOR test phase. The involvement of CB 1 Rs was assessed by using the CB 1 R antagonist, AM251 (3 mg/kg, i.p.). WIN 55,212-2 caused a disruption in NOR, an action absent in mice also receiving AM251, KW-6002 or SCH 58261 during the encoding/consolidation phase; SCH 58251 was ineffective if present during retrieval only. No effects were detected in the Elevated Plus maze or Open Field Test. The finding that CB 1 R-mediated memory disruption is prevented by antagonism of adenosine A 2A Rs, highlights a possibility to prevent cognitive side effects when therapeutic application of CB 1 R drugs is desired. Copyright © 2017 Elsevier Ltd. All rights reserved.

Un cas particulier du scénario dans l'apprentissage des langues : le labyrinthe (action maze Action Mazes: a special case of the scenario for language learning

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Joseph Rézeau

2008-03-01

Full Text Available En didactique des langues l'approche actionnelle et les scénarios sont d'actualité, en lien avec les Tice (Technologies de l'Information et de la Communication pour l'Enseignement. Cependant, des activités de type labyrinthe (action mazes, courantes dans les années 1980 et souvent portées sur les micro-ordinateurs de l'époque, semblent quelque peu tombées dans l'oubli. Cet article entend montrer qu'il est relativement aisé de concevoir et de réaliser de telles activités sur une plateforme d'enseignement à distance telle que Moodle. Nous analyserons également l'impact d'une activité de type labyrinthe sur une population d'étudiants dans le cadre d'un enseignement d'anglais de type Lansad (langues pour spécialistes d'autres disciplines.The development of ICT in language teaching concurs with an interest in task-based approaches and scenarios. Surprisingly, however, such activities as "adventure games" and "action mazes" which were quite popular in CALL (Computer Assisted Language Learning in the 1980s seem to have fallen into oblivion. This article aims at demonstrating that it is relatively easy to design and implement "action mazes" on an LMS (Learning Management System such as Moodle. We shall then analyse the impact of an "action maze" learning activity on a population of students of ESP (English for Specific Purposes.

A materials test system for static compression at elevated temperatures

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Korellis, J. S.; Steinhaus, C. A.; Totten, J. J.

1992-06-01

This report documents modifications to our existing computer-controlled compression testing system to allow elevated temperature testing in an evacuated environment. We have adopted an 'inverse' design configuration where the evacuated test volume is located within the induction heating coil, eliminating the expense and minimizing the evacuation time of a much larger traditional vacuum chamber.

The effect of a paraffin screen on the neutron dose at the maze door of a 15 MV linear accelerator.

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Krmar, M; Nikolić, D; Kuzmanović, A; Kuzmanović, Z; Ganezer, K

2013-08-01

The purpose of this study was to explore the effects of a paraffin screen located at various positions in the maze on the neutron dose equivalent at the maze door. The neutron dose equivalent was measured at the maze door of a room containing a 15 MV linear accelerator for x-ray therapy. Measurements were performed for several positions of the paraffin screen covering only 27.5% of the cross-sectional area of the maze. The neutron dose equivalent was also measured at all screen positions. Two simple models of the neutron source were considered in which the first assumed that the source was the cross-sectional area at the inner entrance of the maze, radiating neutrons in an isotropic manner. In the second model the reduction in the neutron dose equivalent at the maze door due to the paraffin screen was considered to be a function of the mean values of the neutron fluence and energy at the screen. The results of this study indicate that the equivalent dose at the maze door was reduced by a factor of 3 through the use of a paraffin screen that was placed inside the maze. It was also determined that the contributions to the dosage from areas that were not covered by the paraffin screen as viewed from the dosimeter, were 2.5 times higher than the contributions from the covered areas. This study also concluded that the contributions of the maze walls, ceiling, and floor to the total neutron dose equivalent were an order of magnitude lower than those from the surface at the far end of the maze. This study demonstrated that a paraffin screen could be used to reduce the neutron dose equivalent at the maze door by a factor of 3. This paper also found that the reduction of the neutron dose equivalent was a linear function of the area covered by the maze screen and that the decrease in the dose at the maze door could be modeled as an exponential function of the product φ·E at the screen.

Neural and Behavioral Correlates of PTSD and Alcohol Use

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2014-12-01

Rezayof A, Hosseini SS, Zarrindast MR (2009) Effects of Morphine on Rat Behaviour in the Elevated Plus Maze: The Role of Central Amygdala Dopamine...The current research takes a multi-level approach to study the psychological , behavioral, cognitive and neural relationships between PTSD and alcohol...presented with combat-associated stimuli, an effect mediated by the anterior cingulate cortex. PTSD was associated with heightened anterior cingulate

Modification of Anxious Behavior after Psychogenic Trauma and Treatment with Galanin Receptor Antagonist.

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Lyudyno, V I; Tsikunov, S G; Abdurasulova, I N; Kusov, A G; Klimenko, V M

2015-07-01

Effects of blockage of central galanin receptors on anxiety manifestations were studied in rats with psychogenic trauma. Psychogenic trauma was modeled by exposure of a group of rats to the situation when the partner was killed by a predator. Antagonist of galanin receptors was intranasally administered before stress exposure. Animal behavior was evaluated using the elevated-plus maze test, free exploratory paradigm, and open-field test. Psychogenic trauma was followed by an increase in anxiety level and appearance of agitated behavior. Blockage of galanin receptors aggravated behavioral impairment, which manifested in the pathological anxious reactions - manifestations of hypervigilance and hyperawareness. The results suggest that endogenous pool of galanin is involved into prevention of excessive CNS response to stressful stimuli typical of posttraumatic stress disorder.

Mechanism of the Interaction of Cannabinoid System in Central Amygdale with Opioid System

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S. Sarahroodi

2008-01-01

Full Text Available Background and objectivesCannabinoids which are active compounds of marijuana show some pharmacological effects similar to the opioids. There are also functional interactions between both cannabinoid and opioid systems. In this study we investigated the role of cannabinoid receptors in central amygdala and its interaction with opioid system.MethodsIn the present study, we investigated the effects of intraperitoneal injection of opioid drugs on response-induced by intra-amygdala (intra-Amyg microinjection of cannabinoid agents in rats, using elevated plus-maze test of anxiety. ResultsIntraperitoneal injection of morphine (3, 6 and 9 mg/kg increased %OAT and %OAE, but not locomotor activity, showing an anxiolytic response. However, some doses of the opioid receptor antagonist, naloxone reduced %OAT and locomotor activity as well. Intra-Amyg administration of CB1 cannabinoid receptor agonist, ACPA (at the dose of 1.25 and 5 ng/rat increased %OAT and %OAE but not locomotor activity, thus showing an anxiolytic response, which was increased by morphine (6 mg/kg, i.p. without any interaction. Naloxone also reduced ACPA effects. Intra-Amyg administration of CB1 cannabinoid receptor antagonist, AM251 (2.5, 25 and 100 ng/rat did not alter %OAT and %OAE but higher doses of drug (25 and 100 ng/rat reduced locomotor activity. However, the drug in combination of morphine anxiolytic response and with naloxone decreased anxiety.ConclusionThe results may indicate an anxiolytic for CB1 cannabinoid. Our results also showed that opioid system may have interaction with cannabinoid receptor in the amygdale. Keywords: Cannabinoids, Morphine; Naloxone, Anxiety, Elevated Plus-Maze

Chronic caffeine consumption prevents cognitive decline from young to middle age in rats, and is associated with increased length, branching, and spine density of basal dendrites in CA1 hippocampal neurons.

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Vila-Luna, S; Cabrera-Isidoro, S; Vila-Luna, L; Juárez-Díaz, I; Bata-García, J L; Alvarez-Cervera, F J; Zapata-Vázquez, R E; Arankowsky-Sandoval, G; Heredia-López, F; Flores, G; Góngora-Alfaro, J L

2012-01-27

Chronic caffeine consumption has been inversely associated with the risk of developing dementia and Alzheimer's disease. Here we assessed whether chronic caffeine treatment prevents the behavioral and cognitive decline that male Wistar rats experience from young (≈3 months) to middle age (≈10 months). When animals were young they were evaluated at weekly intervals in three tests: motor activity habituation in the open field (30-min sessions at the same time on consecutive days), continuous spontaneous alternation in the Y-maze (8 min), and elevated plus-maze (5 min). Afterward, rats from the same litter were randomly assigned either to a caffeine-treated group (n=13) or a control group (n=11), which received only tap water. Caffeine treatment (5 mg/kg/day) began when animals were ≈4 months old, and lasted for 6 months. Behavioral tests were repeated from day 14 to day 28 after caffeine withdrawal, a time period that is far in excess for the full excretion of a caffeine dose in this species. Thirty days after caffeine discontinuation brains were processed for Golgi-Cox staining. Compared with controls, we found that middle-aged rats that had chronically consumed low doses of caffeine (1) maintained their locomotor habituation during the second consecutive day exposure to the open field (an index of non-associative learning), (2) maintained their exploratory drive to complete the conventional minimum of nine arm visits required to calculate the alternation performance in the Y-maze in a greater proportion, (3) maintained their alternation percentage above chance level (an index of working memory), and (4) did not increase the anxiety indexes assessed by measuring the time spent in the open arms of the elevated plus maze. In addition, morphometric analysis of hippocampal neurons revealed that dendritic branching (90-140 μm from the soma), length of 4th and 5th order branches, total dendritic length, and spine density in distal dendritic branches were greater in

Anxiolytic-like and sedative effects of Hydrocotyle umbellata L., Araliaceae, extract in mice

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Fábio F. Rocha

2011-02-01

Full Text Available The plant Hydrocotyle umbellata L., Araliaceae (water pennywort, is widely used in Brazilian folk medicine to reduce anxiety. This work investigates the anxiolytic-like effects of the ethanol extract from H. umbellata subterraneous parts as well as the extract's other putative central nervous system effects that could justify its common use. Oral dosing of the extract (0.3 and 1 g/kg clearly showed an anxiolytic-like profile in the elevated plus maze test where it increased the percentage of entries into and the time spent in the open arms of the maze. In the marble-burying test, the extract induced anxiolytic-like effects only at a dose of 1 g/kg, which also causes mild sedative properties in other models. The sedated state was characterized by a slight reduction in spontaneous exploratory activity during the open field test and a potentiating of pentobarbital-induced hypnosis. No signs of motor impairment were detected in the rota rod or chimney tests. The extract did not show antidepressant properties in mice as assessed by the forced swimming test. These results support the use of H. umbellata in Brazilian folk medicine as an anxiolytic and contribute to the scientific knowledge of this possible phytotherapeutic resource.

A novel radial water tread maze tracks age-related cognitive decline in mice

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Christina Pettan-Brewer

2013-10-01

Full Text Available There is currently no treatment and cure for age-related dementia and cognitive impairment in humans. Mice suffer from age-related cognitive decline just as people do, but assessment is challenging because of cumbersome and at times stressful performance tasks. We developed a novel radial water tread (RWT maze and tested male C57BL/6 (B6 and C57BL/6 x Balb/c F1 (CB6F1 mice at ages 4, 12, 20, and 28 months. B6 mice showed a consistent learning experience and memory retention that gradually decreased with age. CB6F1 mice showed a moderate learning experience in the 4 and 12 month groups, which was not evident in the 20 and 28 month groups. In conclusion, CB6F1 mice showed more severe age-related cognitive impairment compared to B6 mice and might be a suitable model for intervention studies. In addition, the RWT maze has a number of operational advantages compared to currently accepted tasks and can be used to assess age-related cognition impairment in B6 and CB6F1 mice as early as 12 months of age.

GABA(A) receptor antagonism in the ventrocaudal periaqueductal gray increases anxiety in the anxiety-resistant postpartum rat.

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Miller, Stephanie M; Piasecki, Christopher C; Peabody, Mitchell F; Lonstein, Joseph S

2010-06-01

Postpartum mammals show suppressed anxiety, which is necessary for their ability to appropriately care for offspring. It is parsimonious to suggest that the neurobiological basis of this reduced anxiety is similar to that of non-parturient animals, involving GABA(A) receptor activity in sites including the midbrain periaqueductal gray (PAG). In Experiment 1, postpartum and diestrous virgin female rats received an intraperitoneal injection of the GABA(A) receptor antagonist (+)-bicuculline (0, 2 and 4 mg/kg) and anxiety-related behavior was assessed with an elevated plus maze. The 4 mg/kg dose of (+)-bicuculline significantly increased anxiety-related behavior, particularly in the postpartum females. Experiment 2 revealed that bicuculline's action was within the central nervous system, because anxiety in neither dams nor virgins was significantly affected by intraperitoneal injection of bicuculline methiodide (0, 2 and 6 mg/kg), which does not readily cross the blood-brain-barrier. In Experiment 3, bicuculline methiodide (2.5 ng/side) was directly infused into the ventrocaudal PAG (cPAGv) and significantly increased dams' anxiety compared to saline-infused controls. These studies expand our knowledge of how GABA(A) receptor modulators affect anxiety behaviors in postpartum rats to the widely-used elevated plus maze, and indicate that the postpartum suppression of anxiety is in part a consequence of elevated GABAergic neurotransmission in the cPAGv. Copyright 2010 Elsevier Inc. All rights reserved.

Cross-fostering does not alter the neurochemistry or behavior of spontaneously hypertensive rats

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Russell Vivienne A

2009-06-01

Full Text Available Abstract Background Attention-deficit/hyperactivity disorder (ADHD is a highly heritable developmental disorder resulting from complex gene-gene and gene-environment interactions. The most widely used animal model, the spontaneously hypertensive rat (SHR, displays the major symptoms of ADHD (deficits in attention, impulsivity and hyperactivity and has a disturbance in the noradrenergic system when compared to control Wistar-Kyoto rats (WKY. The aim of the present study was to determine whether the ADHD-like characteristics of SHR were purely genetically determined or dependent on the gene-environment interaction provided by the SHR dam. Methods SHR/NCrl (Charles River, USA, WKY/NCrl (Charles River, USA and Sprague Dawley rats (SD/Hsd, Harlan, UK were bred at the University of Cape Town. Rat pups were cross-fostered on postnatal day 2 (PND 2. Control rats remained with their birth mothers to serve as a reference for their particular strain phenotype. Behavior in the open-field and the elevated-plus maze was assessed between PND 29 and 33. Two days later, rats were decapitated and glutamate-stimulated release of [3H]norepinephrine was determined in prefrontal cortex and hippocampal slices. Results There was no significant effect of "strain of dam" but there was a significant effect of "pup strain" on all parameters investigated. SHR pups travelled a greater distance in the open field, spent a longer period of time in the inner zone and entered the inner zone of the open-field more frequently than SD or WKY. SD were more active than WKY in the open-field. WKY took longer to enter the inner zone than SHR or SD. In the elevated-plus maze, SHR spent less time in the closed arms, more time in the open arms and entered the open arms more frequently than SD or WKY. There was no difference between WKY and SD behavior in the elevated-plus maze. SHR released significantly more [3H]norepinephrine in response to glutamate than SD or WKY in both hippocampus

In Situ Elevated Temperature Testing of Fly Ash Based Geopolymer Composites

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Vickers, Les; Pan, Zhu; Tao, Zhong; van Riessen, Arie

2016-01-01

In situ elevated temperature investigations using fly ash based geopolymers filled with alumina aggregate were undertaken. Compressive strength and short term creep tests were carried out to determine the onset temperature of viscous flow. Fire testing using the standard cellulose curve was performed. Applying a load to the specimen as the temperature increased reduced the temperature at which viscous flow occurred (compared to test methods with no applied stress). Compressive strength increased at the elevated temperature and is attributed to viscous flow and sintering forming a more compact microstructure. The addition of alumina aggregate and reduction of water content reduced the thermal conductivity. This led to the earlier onset and shorter dehydration plateau duration times. However, crack formation was reduced and is attributed to smaller thermal gradients across the fire test specimen. PMID:28773568

In Situ Elevated Temperature Testing of Fly Ash Based Geopolymer Composites

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Les Vickers

2016-06-01

Full Text Available In situ elevated temperature investigations using fly ash based geopolymers filled with alumina aggregate were undertaken. Compressive strength and short term creep tests were carried out to determine the onset temperature of viscous flow. Fire testing using the standard cellulose curve was performed. Applying a load to the specimen as the temperature increased reduced the temperature at which viscous flow occurred (compared to test methods with no applied stress. Compressive strength increased at the elevated temperature and is attributed to viscous flow and sintering forming a more compact microstructure. The addition of alumina aggregate and reduction of water content reduced the thermal conductivity. This led to the earlier onset and shorter dehydration plateau duration times. However, crack formation was reduced and is attributed to smaller thermal gradients across the fire test specimen.

Effects of periadolescent fluoxetine and paroxetine on elevated plus-maze, acoustic startle, and swimming immobility in rats while on and off-drug

OpenAIRE

Williams Michael T; Skelton Matthew R; Morford LaRonda R; Graham Devon L; Vorhees Charles V

2011-01-01

Abstract Rationale Whether selective serotonin reuptake inhibitors (SSRIs) exposure during adolescent brain development causes lasting effects remains unresolved. Objective Assess the effects of fluoxetine and paroxetine 60 days after adolescent exposure compared with when on-drug. Methods Male Sprague-Dawley littermates (41 litters) were gavaged on postnatal days 33-53 with fluoxetine (3 or 10 mg/kg/day), paroxetine (3, 10 or, 17 mg/kg/day), or water; half were tested while on-drug (21 litte...

Central depressant activity of butanol fraction of Securinega virosa root bark in mice.

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Magaji, Mohammed Garba; Yaro, Abdullahi Hamza; Musa, Aliyu Muhammad; Anuka, Joseph Akponso; Abdu-Aguye, Ibrahim; Hussaini, Isa Marte

2012-05-07

Securinega virosa is a commonly used medicinal plant in African traditional medicine in the management of epilepsy and mental illness. Previous studies in our laboratory showed that the crude methanol root bark extract of the plant possesses significant behavioral effect in laboratory animals. In an attempt to isolate and characterize the biological principles responsible for the observed activity, this study is aimed at evaluating the central depressant activity of the butanol fraction of the methanol root bark extract of Securinega virosa. The medial lethal dose of the butanol fraction was estimated using the method of Lorke. Preliminary phytochemical screening was conducted on the butanol fraction using standard protocol. The behavioral effect of the butanol fraction (75, 150 and 300mg/kg) was evaluated using diazepam induced sleep test, hole-board test, beam walking assay, staircase test, open field test and elevated plus maze assay, all in mice. The median lethal dose of the butanol fraction was estimated to be 1256.9mg/kg. The preliminary phytochemical screening revealed the presence of tannins, saponins, alkaloids, flavonoids, cardiac glycosides, similar to those found in the crude methanol extract. The butanol fraction significantly (Ptime taken to complete the task and number of foot slips in the beam walking assay, suggesting that it does not induce significant motor coordination deficit. Diazepam (2mg/kg), the standard agent used significantly (Popen field test, the butanol fraction significantly reduced the number of square crossed as well as the number of rearing. However, the butanol fraction did not significantly alter the behavior of mice in the elevated plus maze assay, while diazepam (0.5mg/kg) significantly (Ptime spent in the open arm and reduced the number of closed arm entry. The findings of this study suggest that the butanol fraction of Securinega virosa root bark contains some bioactive principles that are sedative in nature. Copyright �

Capturing both the cognitive and emotional features of post-traumatic stress disorder (PTSD in rats: An updated animal model

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Andrea eBerardi

2014-04-01

Full Text Available The new-released Diagnostic and Statistical Manual of Mental Disorders (DSM-5 defines post-traumatic stress disorder (PTSD as a trauma and stressor-related disorder. PTSD pathogenesis relies on paradoxical changes of emotional memory processing induced by the trauma exposure and associated with emotional dysfunction. Several animal models of PTSD have been validated and are currently used. Each one mimics a particular subset of the disorder with particular emphasis, mainly driven by the past classification of PTSD in the DSM-4, on the emotional features. In view of the recent update in the DSM-5, our aim was to develop, by using well-validated paradigms, a modified model of PTSD able to mimic at the same time both the cognitive and emotional features of the disease. We exposed male rats to either a piece of worn cat collar or to a series of inescapable footshocks paired with a PTSD risk factor, i.e. social isolation. Animals were subsequently re-exposed to the conditioned contexts at different time intervals in order to test memory retention for the stressors. In addition, footshock-exposed rats were tested in the elevated-plus-maze and social interaction tests. We found that rats exposed to a cat collar exhibited an acute fear response that did not lead to enduring memory retention. Conversely, footshock-exposed rats expressed a successful retention of the stressful experience at 1, 7, 14, 21 and 56 post-exposure days. Footshock-exposed rats displayed an anxious behavioral profile in the social interaction test and a significantly reduced locomotor activity in the elevated-plus-maze test. These dysfunctions were not observed when animals were socially housed, thus highlighting a social buffer effect in the development of the pathology. Our results underline the good validity of a footshock-based paradigm paired with social isolation as a PTSD animal model, able to mimic at the same time both some of the enduring cognitive and emotional facets

On the tenth value distance of the photon field along the maze of high-energy linear accelerator vaults.

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Han, Zhaohui; Chin, Lee M

2018-03-01

There is a wide range in the reported photon tenth value distance (TVD) in the maze of high-energy linear accelerator vaults. In order to gain insight into the appropriate use of the TVD value during door design, we performed measurements of the photon dose in the maze of four vaults. In addition, our study represents the first to describe a scenario where an inner borated polyethylene (BPE) door for neutron shielding is installed in the maze downstream to Point A, the point on the maze centerline that is just visible from the isocenter. The measurements were made along the maze centerline at 1 m above the floor. In all cases, the accelerator operated at a nominal energy of 15 MV. Of the four vaults, three were equipped with an inner BPE door at a distance of 1.0-2.1 m downstream to Point A. The door was made of 10.16 cm (4″) BPE sandwiched between two 0.635 cm (1/4″) steel face plates. The photon dose in the maze without a BPE door decreases exponentially with a characteristic TVD of 6 m beyond a distance of 2.5 m from Point A. The presence of a BPE door in an identical vault not only reduces the photon intensity in the maze by about an order of magnitude, but also softens the energy spectrum with a shortened TVD of 4.7 m, significantly lessening the shielding burden at the outer maze entrance. In contrast to the common use of Point A as the reference point to specify distance, the photon dose in the maze with a BPE door located downstream to Point A can be satisfactorily described as exponential functions of the distance measured from the door, which shows good consistency among the three vaults of different room parameters. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Sex matters: females in proestrus show greater diazepam anxiolysis and brain-derived neurotrophin factor- and parvalbumin-positive neurons than males.

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Ravenelle, Rebecca; Berman, Ariel K; La, Jeffrey; Mason, Briana; Asumadu, Evans; Yelleswarapu, Chandra; Donaldson, S Tiffany

2018-04-01

In humans and animal models, sex differences are reported for anxiety-like behavior and response to anxiogenic stimuli. In the current work, we studied anxiety-like behavior and response to the prototypical anti-anxiety drug, diazepam. We used 6th generation outbred lines of adult Long Evans rats with high and low anxiety-like behavior phenotypes to investigate the impact of proestrus on the baseline and diazepam-induced behavior. At three doses of diazepam (0, 0.1, and 1.0 mg/kg, i.p.), we measured anxiogenic responses on the elevated plus maze of adult male and female rats. We assessed parvalbumin and brain-derived neurotrophin protein levels in forebrain and limbic structures implicated in anxiety/stress using immunohistochemistry. At baseline, we saw significant differences between anxiety lines, with high anxiety lines displaying less time on the open arms of the elevated plus maze, and less open arm entries, regardless of sex. During proestrus, high anxiety females showed less anxiety-like behavior at 0.1 mg/kg, while low anxiety females displayed less anxiety-like behavior at 0.1 and 1.0 doses, relative to males. Brain-derived neurotrophin protein was elevated in females in the medial prefrontal cortex and central amygdala, while parvalbumin-immunoreactive cells were greater in males in the medial prefrontal cortex. Parvalbumin-positive cells in high anxiety females were higher in CA2 and dentate gyrus relative to males from the same line. In sum, when tested in proestrus, females showed greater anxiolytic effects of diazepam relative to males, and this correlated with increases in neurotrophin and parvalbumin neuron density in corticolimbic structures. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Neural correlates of olfactory and visual memory performance in 3D-simulated mazes after intranasal insulin application.

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Brünner, Yvonne F; Rodriguez-Raecke, Rea; Mutic, Smiljana; Benedict, Christian; Freiherr, Jessica

2016-10-01

This fMRI study intended to establish 3D-simulated mazes with olfactory and visual cues and examine the effect of intranasally applied insulin on memory performance in healthy subjects. The effect of insulin on hippocampus-dependent brain activation was explored using a double-blind and placebo-controlled design. Following intranasal administration of either insulin (40IU) or placebo, 16 male subjects participated in two experimental MRI sessions with olfactory and visual mazes. Each maze included two separate runs. The first was an encoding maze during which subjects learned eight olfactory or eight visual cues at different target locations. The second was a recall maze during which subjects were asked to remember the target cues at spatial locations. For eleven included subjects in the fMRI analysis we were able to validate brain activation for odor perception and visuospatial tasks. However, we did not observe an enhancement of declarative memory performance in our behavioral data or hippocampal activity in response to insulin application in the fMRI analysis. It is therefore possible that intranasal insulin application is sensitive to the methodological variations e.g. timing of task execution and dose of application. Findings from this study suggest that our method of 3D-simulated mazes is feasible for studying neural correlates of olfactory and visual memory performance. Copyright © 2016 Elsevier Inc. All rights reserved.

Maze solving algorithm and its programs using Z-80 assembler language for a robot

Energy Technology Data Exchange (ETDEWEB)

Takeno, J; Mukaidono, M

1982-01-01

In the first part the formation of a maze problem is introduced and the outline of this algorithm to solve a maze is explained in the second part. The third part describes the detail of this program, and the final part shows the program which has been developed using Z-80 assembler language. This program has portability for other robots using Z-80 microprocessors. 7 references.

Identifying the appropriate time for deep brain stimulation to achieve spatial memory improvement on the Morris water maze.

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Jeong, Da Un; Lee, Jihyeon; Chang, Won Seok; Chang, Jin Woo

2017-03-07

The possibility of using deep brain stimulation (DBS) for memory enhancement has recently been reported, but the precise underlying mechanisms of its effects remain unknown. Our previous study suggested that spatial memory improvement by medial septum (MS)-DBS may be associated with cholinergic regulation and neurogenesis. However, the affected stage of memory could not be distinguished because the stimulation was delivered during the execution of all memory processes. Therefore, this study was performed to determine the stage of memory affected by MS-DBS. Rats were administered 192 IgG-saporin to lesion cholinergic neurons. Stimulation was delivered at different times in different groups of rats: 5 days before the Morris water maze test (pre-stimulation), 5 days during the training phase of the Morris water maze test (training-stimulation), and 2 h before the Morris water maze probe test (probe-stimulation). A fourth group of rats was lesioned but received no stimulation. These four groups were compared with a normal (control) group. The most effective memory restoration occurred in the pre-stimulation group. Moreover, the pre-stimulation group exhibited better recall of the platform position than the other stimulation groups. An increase in the level of brain derived neurotrophic factor (BDNF) was observed in the pre-stimulation group; this increase was maintained for 1 week. However, acetylcholinesterase activity in the pre-stimulation group was not significantly different from the lesion group. Memory impairment due to cholinergic denervation can be improved by DBS. The improvement is significantly correlated with the up-regulation of BDNF expression and neurogenesis. Based on the results of this study, the use of MS-DBS during the early stage of disease may restore spatial memory impairment.

Neonatal stress-induced affective changes in adolescent Wistar rats: early signs of schizophrenia-like behavior

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Carlos Eduardo Neves Girardi

2014-09-01

Full Text Available Psychiatric disorders are multifactorial diseases with etiology that may involve genetic factors, early life environment and stressful life events. The neurodevelopmental hypothesis of schizophrenia is based on a wealth of data on increased vulnerability in individuals exposed to insults during the perinatal period. Maternal deprivation disinhibits the adrenocortical response to stress in neonatal rats and has been used as an animal model of schizophrenia. To test if long-term affective consequences of early life stress were influenced by maternal presence, we submitted 10-day old rats, either deprived (for 22 h or not from their dams, to a stress challenge (i.p. saline injection. Corticosterone plasma levels were measured 2 h after the challenge, whereas another subgroup was assessed for behavior in the open field, elevated plus maze, social investigation and the negative contrast sucrose consumption test in adolescence (postnatal day 45. Maternally deprived rats exhibited increased plasma corticosterone levels which were higher in maternally deprived and stress challenged pups. Social investigation was impaired in maternally deprived rats only, while saline injection, independently of maternal deprivation, was associated with increased anxiety-like behavior in the elevated plus maze and an impaired intake decrement in the negative sucrose contrast. In the open field, center exploration was reduced in all maternally-deprived adolescents and in control rats challenged with saline injection. The most striking finding was that exposure to a stressful stimulus per se, regardless of maternal deprivation, was linked to differential emotional consequences. We therefore propose that besides being a well-known and validated model of schizophrenia in adult rats, the maternal deprivation paradigm could be extended to model early signs of psychiatric dysfunction, and would particularly be a useful tool to detect early signs that resemble schizophrenia.

Consumption of fig fruits grown in Oman can improve memory, anxiety, and learning skills in a transgenic mice model of Alzheimer's disease.

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Subash, Selvaraju; Essa, Musthafa Mohamed; Braidy, Nady; Al-Jabri, Ahood; Vaishnav, Ragini; Al-Adawi, Samir; Al-Asmi, Abdullah; Guillemin, Gilles J

2016-12-01

Alzheimer disease (AD) is one of the most common forms of dementia in the elderly. Several reports have suggested neurotoxic effects of amyloid beta protein (Aβ) and role of oxidative stress in AD. Figs are rich in fiber, copper, iron, manganese, magnesium, potassium, calcium, vitamin K, and are a good source of proanthocyanidins and quercetin which demonstrate potent antioxidant properties. We studied the effect of dietary supplementation with 4% figs grown in Oman on the memory, anxiety, and learning skills in APPsw/Tg2576 (Tg mice) mice model for AD. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4 months and after 15 months using the Morris water maze test, rota-rod test, elevated plus maze test, and open-field test. Tg mice that were fed a control diet without figs showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial, position discrimination learning ability, and motor coordination compared to the wild-type control mice on the same diet, and Tg mice fed on 4% fig diet supplementation for 15 months. Our results suggest that dietary supplementation of figs may be useful for the improvement of cognitive and behavioral deficits in AD.

Use of the Open Field Maze to measure locomotor and anxiety-like behavior in mice.

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Seibenhener, Michael L; Wooten, Michael C

2015-02-06

Animal models have proven to be invaluable to researchers trying to answer questions regarding the mechanisms of behavior. The Open Field Maze is one of the most commonly used platforms to measure behaviors in animal models. It is a fast and relatively easy test that provides a variety of behavioral information ranging from general ambulatory ability to data regarding the emotionality of the subject animal. As it relates to rodent models, the procedure allows the study of different strains of mice or rats both laboratory bred and wild-captured. The technique also readily lends itself to the investigation of different pharmacological compounds for anxiolytic or anxiogenic effects. Here, a protocol for use of the open field maze to describe mouse behaviors is detailed and a simple analysis of general locomotor ability and anxiety-related emotional behaviors between two strains of C57BL/6 mice is performed. Briefly, using the described protocol we show Wild Type mice exhibited significantly less anxiety related behaviors than did age-matched Knock Out mice while both strains exhibited similar ambulatory ability.

Radiation protection of cyclotron vault with maze in PET Cyclotron Center

International Nuclear Information System (INIS)

Fueloep, Marko

2003-01-01

The PET Cyclotron center (PCC) is a complex for production, research and application of positron radiopharmaceuticals for PET (Positron Emission Tomography), which was commissioned this year (2004) in Bratislava, Slovak Republic. Positron radionuclides are produced by 18/9 MeV proton/deuteron cyclotron CYCLONE 18/9. Radiation protection of personnel and inhabitants against ionizing radiation in the PCC is solved with regard to the ICRP recommendations and Slovak regulatory system, protection rules and criteria and optimization of radiation protection. In the article comparisons of calculated and measured neutron and gamma dose equivalent rates around the CYCLONE 18/9 and at various points behind the shielding of cyclotron vault with maze are presented. Description of the CYCLONE 18/9 as a source of angular distribution of neutron energy spectra (production of 18 F was considered) was simulated by Monte Carlo code MCNPX. Code MCNP4B was used for shielding calculation of cyclotron vault with maze. Neutron energy spectra behind the shielding were measured by Bonner spectrometer. The values of neutron dose equivalent, which were calculated and measured around the CYCLONE 18/9 and at various points behind the shielding of cyclotron vault with maze, are within the range of factor 2. (authors)

Pregnanolone Glutamate, a Novel Use-Dependent NMDA Receptor Inhibitor, Exerts Antidepressant-Like Properties in Animal Models.

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Holubova, Kristina; Nekovarova, Tereza; Pistovcakova, Jana; Sulcova, Alexandra; Stuchlík, Ales; Vales, Karel

2014-01-01

A number of studies demonstrated a rapid onset of an antidepressant effect of non-competitive N-methyl-d-aspartic acid receptor (NMDAR) antagonists. Nonetheless, its therapeutic potential is rather limited, due to a high coincidence of negative side-effects. Therefore, the challenge seems to be in the development of NMDAR antagonists displaying antidepressant properties, and at the same time maintaining regular physiological function of the NMDAR. Previous results demonstrated that naturally occurring neurosteroid 3α5β-pregnanolone sulfate shows pronounced inhibitory action by a use-dependent mechanism on the tonically active NMDAR. The aim of the present experiments is to find out whether the treatment with pregnanolone 3αC derivatives affects behavioral response to chronic and acute stress in an animal model of depression. Adult male mice were used throughout the study. Repeated social defeat and forced swimming tests were used as animal models of depression. The effect of the drugs on the locomotor/exploratory activity in the open-field test was also tested together with an effect on anxiety in the elevated plus maze. Results showed that pregnanolone glutamate (PG) did not induce hyperlocomotion, whereas both dizocilpine and ketamine significantly increased spontaneous locomotor activity in the open field. In the elevated plus maze, PG displayed anxiolytic-like properties. In forced swimming, PG prolonged time to the first floating. Acute treatment of PG disinhibited suppressed locomotor activity in the repeatedly defeated group-housed mice. Aggressive behavior of isolated mice was reduced after the chronic 30-day administration of PG. PG showed antidepressant-like and anxiolytic-like properties in the used tests, with minimal side-effects. Since PG combines GABAA receptor potentiation and use-dependent NMDAR inhibition, synthetic derivatives of neuroactive steroids present a promising strategy for the treatment of mood disorders. -3α5�

A comparison of computerized adaptive testing and fixed-length short forms for the Prosthetic Limb Users Survey of Mobility (PLUS-MTM).

Science.gov (United States)

Amtmann, Dagmar; Bamer, Alyssa M; Kim, Jiseon; Bocell, Fraser; Chung, Hyewon; Park, Ryoungsun; Salem, Rana; Hafner, Brian J

2017-09-01

New health status instruments can be administered by computerized adaptive test or short forms. The Prosthetic Limb Users Survey of Mobility (PLUS-M TM ) is a self-report measure of mobility for prosthesis users with lower limb loss. This study used the PLUS-M to examine advantages and disadvantages of computerized adaptive test and short forms. To compare scores obtained from computerized adaptive test to scores obtained from fixed-length short forms (7-item and 12-item) in order to provide guidance to researchers and clinicians on how to select the best form of administration for different uses. Cross-sectional, observational study. Individuals with lower limb loss completed the PLUS-M by computerized adaptive test and short forms. Administration time, correlations between the scores, and standard errors were compared. Scores and standard errors from the computerized adaptive test, 7-item short form, and 12-item short form were highly correlated and all forms of administration were efficient. Computerized adaptive test required less time to administer than either paper or electronic short forms; however, time savings were minimal compared to the 7-item short form. Results indicate that the PLUS-M computerized adaptive test is most efficient, and differences in scores between administration methods are minimal. The main advantage of the computerized adaptive test was more reliable scores at higher levels of mobility compared to short forms. Clinical relevance Health-related item banks, like the Prosthetic Limb Users Survey of Mobility (PLUS-M TM ), can be administered by computerized adaptive testing (CAT) or as fixed-length short forms (SFs). Results of this study will help clinicians and researchers decide whether they should invest in a CAT administration system or whether SFs are more appropriate.

Reducing elevator energy use: A comparison of posted feedback and reduced elevator convenience

Science.gov (United States)

Houten, Ron Van; Nau, Paul A.; Merrigan, Michael

1981-01-01

The effects of two different procedures for reducing elevator energy use were assessed using a multiple-baseline design. In the first procedure, feedback about the amount of energy consumed by the elevators each week was posted on each elevator door. Later, signs advocating the use of stairs to save energy and improve health were posted next to the feedback signs. In the second procedure, the time required to travel between floors was increased by adding a delay to the elevator door closing mechanisms. Results indicated that neither feedback alone nor feedback plus educational signs reduced the amount of energy consumed by the elevators. However, use of the door delay reduced consumption by one-third in all elevators. A second experiment replicated the effect of the door delay on energy consumption and, in addition, demonstrated that the door delay also produced a reduction in the number of persons using the elevator. The second experiment also showed that, following an initial period during which a full delay was in effect, a gradual reduction of the delay interval resulted in continued energy conservation. Reduced convenience as a general strategy for energy conservation is discussed. PMID:16795648

High speed elevator s rise high rise building; Chokoso biru wo kakenoboru elevator

Energy Technology Data Exchange (ETDEWEB)

Tanabe, K. [Mitsubishi Electric Corp., Tokyo (Japan)

1994-10-20

The world`s fastest (750 m/min) elevators are operating in Yokohama Landmark Tower. This paper describes how engineers solved the technological problems to realize the high-speed elevator. Buildings in Japan have become higher and higher. At the present, this Tower is the highest in Japan (296 m, 70 stories). The Ministry of Construction is going to start a research team to study construction of buildings of the order of 1,000 m high. An important issue for a skyscraper is how to reduce the elevator space adapting to the increase of the number of inhabitants in the building. The basic solution is to increase the elevator speed and to plan the best elevator moving line. The 120 kW AC motor direct-driven winding machine that withstands the superhigh-speed suspending load was developed. Vibrations from the motor and the mechanical system are minimized and the touch-down tolerances for the elevator cage are controlled to {plus_minus}15 mm. The safety devices of the elevator include the emergency stopper of special ceramic material and the hydraulic shock absorber with the optimum reduction characteristic. 2 refs., 3 figs.

Aniracetam does not alter cognitive and affective behavior in adult C57BL/6J mice.

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Thomas W Elston

Full Text Available There is a growing community of individuals who self-administer the nootropic aniracetam for its purported cognitive enhancing effects. Aniracetam is believed to be therapeutically useful for enhancing cognition, alleviating anxiety, and treating various neurodegenerative conditions. Physiologically, aniracetam enhances both glutamatergic neurotransmission and long-term potentiation. Previous studies of aniracetam have demonstrated the cognition-restoring effects of acute administration in different models of disease. No previous studies have explored the effects of aniracetam in healthy subjects. We investigated whether daily 50 mg/kg oral administration improves cognitive performance in naïve C57BL/6J mice in a variety of aspects of cognitive behavior. We measured spatial learning in the Morris water maze test; associative learning in the fear conditioning test; motor learning in the accelerating rotarod test; and odor discrimination. We also measured locomotion in the open field test, anxiety through the elevated plus maze test and by measuring time in the center of the open field test. We measured repetitive behavior through the marble burying test. We detected no significant differences between the naive, placebo, and experimental groups across all measures. Despite several studies demonstrating efficacy in impaired subjects, our findings suggest that aniracetam does not alter behavior in normal healthy mice. This study is timely in light of the growing community of healthy humans self-administering nootropic drugs.

Aniracetam Does Not Alter Cognitive and Affective Behavior in Adult C57BL/6J Mice

Science.gov (United States)

Elston, Thomas W.; Pandian, Ashvini; Smith, Gregory D.; Holley, Andrew J.; Gao, Nanjing; Lugo, Joaquin N.

2014-01-01

There is a growing community of individuals who self-administer the nootropic aniracetam for its purported cognitive enhancing effects. Aniracetam is believed to be therapeutically useful for enhancing cognition, alleviating anxiety, and treating various neurodegenerative conditions. Physiologically, aniracetam enhances both glutamatergic neurotransmission and long-term potentiation. Previous studies of aniracetam have demonstrated the cognition-restoring effects of acute administration in different models of disease. No previous studies have explored the effects of aniracetam in healthy subjects. We investigated whether daily 50 mg/kg oral administration improves cognitive performance in naïve C57BL/6J mice in a variety of aspects of cognitive behavior. We measured spatial learning in the Morris water maze test; associative learning in the fear conditioning test; motor learning in the accelerating rotarod test; and odor discrimination. We also measured locomotion in the open field test, anxiety through the elevated plus maze test and by measuring time in the center of the open field test. We measured repetitive behavior through the marble burying test. We detected no significant differences between the naive, placebo, and experimental groups across all measures. Despite several studies demonstrating efficacy in impaired subjects, our findings suggest that aniracetam does not alter behavior in normal healthy mice. This study is timely in light of the growing community of healthy humans self-administering nootropic drugs. PMID:25099639

Effects of acute or chronic ethanol exposure during adolescence on behavioral inhibition and efficiency in a modified water maze task.

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Shawn K Acheson

Full Text Available Ethanol is well known to adversely affect frontal executive functioning, which continues to develop throughout adolescence and into young adulthood. This is also a developmental window in which ethanol is misused by a significant number of adolescents. We examined the effects of acute and chronic ethanol exposure during adolescence on behavioral inhibition and efficiency using a modified water maze task. During acquisition, rats were trained to find a stable visible platform onto which they could escape. During the test phase, the stable platform was converted to a visible floating platform (providing no escape and a new hidden platform was added in the opposite quadrant. The hidden platform was the only means of escape during the test phase. In experiment 1, adolescent animals received ethanol (1.0 g/kg 30 min before each session during the test phase. In experiment 2, adolescent animals received chronic intermittent ethanol (5.0 g/kg for 16 days (PND30 To PND46 prior to any training in the maze. At PND72, training was initiated in the same modified water maze task. Results from experiment 1 indicated that acute ethanol promoted behavioral disinhibition and inefficiency. Experiment 2 showed that chronic intermittent ethanol during adolescence appeared to have no lasting effect on behavioral disinhibition or new spatial learning during adulthood. However, chronic ethanol did promote behavioral inefficiency. In summary, results indicate that ethanol-induced promotion of perseverative behavior may contribute to the many adverse behavioral sequelae of alcohol intoxication in adolescents and young adults. Moreover, the long-term effect of adolescent chronic ethanol exposure on behavioral efficiency is similar to that observed after chronic exposure in humans.

Tactile maze solving in congenitally blind individuals

DEFF Research Database (Denmark)

Gagnon, Léa; Kupers, Ron; Schneider, Fabien C

2010-01-01

and environmental cues such as temperature and echolocation. We hypothesize that by limiting these cues, blind individuals will lose their advantage compared with controls in spatial navigation tasks. We therefore evaluated the performance of blind and sighted individuals in small-scale, tactile multiple T mazes....... Our results show that blindfolded sighted controls outperformed blind participants in the route-learning tasks. This suggests that, contrary to indoor large-scale spaces, navigational skills inside small-scale spaces benefit from visual experience....

Comparing Exploration Strategies for Q-learning in Random Stochastic Mazes

NARCIS (Netherlands)

Tijsma, Arryon; Drugan, Madalina; Wiering, Marco

2016-01-01

Balancing the ratio between exploration and exploitation is an important problem in reinforcement learning. This paper evaluates four different exploration strategies combined with Q-learning using random stochastic mazes to investigate their performances. We will compare: UCB-1, softmax,

Elevated voltage level I.sub.DDQ failure testing of integrated circuits

Science.gov (United States)

Righter, Alan W.

1996-01-01

Burn in testing of static CMOS IC's is eliminated by I.sub.DDQ testing at elevated voltage levels. These voltage levels are at least 25% higher than the normal operating voltage for the IC but are below voltage levels that would cause damage to the chip.

The Aqueous Extract of Portulaca Oleracea Ameliorates Neurobehavioral Dysfunction and Hyperglycemia Related to Streptozotocin-Diabetes Induced in Ovariectomized Rats

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Fatemi Tabatabaei, Seyed Reza; Rashno, Masome; Ghaderi, Shahab; Askaripour, Majid

2016-01-01

Diabetes mellitus is one of the most common causes of neuropathy. Although antioxidant and antidiabetic effects of the aqueous extract of purslane (Portulaca oleracea) (AEOP) have been demonstrated before by other researchers, we did not find any study that assessed the psychobiological effects of AEOP in diabetes induced animals. Thirty ovariectomized (OVX) female Wistar rats were randomly divided into 3 groups of control, Dia and Dia+AEOP. The latter group was orally treated by 300 mg/kg of AEOP for 35 days. Dia and Dia+AEOP groups were made diabetic by IP injection of 60 mg/kg of streptozotocin (STZ). The psychobiological effects of AEOP were assessed by Morris water maze (MWM), elevated plus maze (EPM), forced swimming test (FST) and tail pinch stressor (TPS). AEOP significantly decreased hyperglycemia (p0.05). Diabetes significantly increased their non-functional masticatory activity in TPS (p≤0.001) while it was improved in Dia+AEOP group. We showed that AEOP has significant anxiolytic effects and it can improve spatial cognitive performance, locomotor deficit and stress in diabetic OVX rats. PMID:27642327

Studies on neuropharmacological profile of ethanol extract of Moringa oleifera leaves in mice.

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Bakre, Adewale G; Aderibigbe, Adegbuyi O; Ademowo, Olusegun G

2013-10-07

Moringa oleifera (family Moringaceae), commonly called Horseradish or tree of life, is traditionally used for the treatment of epilepsy and neurologic conditions. The objective of this study is to investigate the neurobehavioural and anticonvulsant properties of the ethanol extract from the leaves of Moringa oleifera. Neurobehavioural properties were evaluated using the open field, hole board, Y-maze, elevated plus maze (EPM) and pentobarbitone-induced hypnosis. Pentylenetetrazole (leptazol), picrotoxin and strychnine induced convulsion tests were used to investigate the anti-convulsive actions of Moringa oleifera. The result showed that the extract (250-2000mg/kg) caused a significant dose-dependent decrease in rearing, grooming, head dips and locomotion (P6.4g/kg. The findings from this study suggest that the ethanol extract of Moringa oleifera leaves possesses CNS depressant and anticonvulsant activities possibly mediated through the enhancement of central inhibitory mechanism involving release γ-amino butyric acid (GABA). The results partially justified the traditional use of the extract for the treatment of epilepsy. © 2013 Elsevier Ireland Ltd. All rights reserved.

Study of sedative preanaesthetic and anxiolytic effects of herbal extract of Tilia platyphyllos scop in comparison with diazepam in the rat

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A Rezaie

2011-05-01

Full Text Available Tilia platyphyllos scop belongs to the Tiliaceae family and mainly grows in northern parts of the country. It has various pharmacological effects including anxiolytic, antibacterial, anticonvulsant, spasmolytic, tranquilization and sedation, hypnotic and muscular relaxation. In order to study sedative, preanaesthetic and anxiolytic effects herbal extract of Tiliaplatyphyllos scop in comparison with diazepam in different groups of female Wistar rats with the same age and weight, doses of 150 mg/kg, 300 mg/kg and  450 mg/kg of herbal extract, 1.2 mg/kg of diazepam and equal volumes of dimethyl sulfoxide as a placebo were injected to rats intraperitoneally 30 minutes prior to evaluation of sedative and preanaesthetic effects (induced sleep duration following 40 mg/kg administration intraperitoneally and anxiolytic effects (using elevated plus maze and Rotarod test. Statistical results obtained represent a significant increase in sleep time induced with ketamine and also a significant increase in time spent by rats in open arms of maze with high and low doses of Tiliaplatyphyllos scop herbal extract (p

Study of sedative, preanaesthetic and anxiolytic effects of herbal extract of Lavandula stoechas in comparison with diazepam in rat

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A Rezaie

2010-11-01

Full Text Available Lavandula stoechas grows naturally in most parts of the world specifically south France, the Mediterranean region and Torento. The plant has various pharmacological properties including analgesic, anti-inflammatory, antidepressant, hypnotic, sedative and tranquilizer, muscle relaxant, anticonvulsant, antibacterial and antispasmodic. For studying the effectiveness of sedative, preanesthetic and anxiolytic effects of Lavandula  stoechas in comparison with diazepam different groups of female Wistar rats with the same age and weight conditions received intraperitoneal injections of Lavandula  stoechas (100, 200, 400 mg/kg, ip, diazepam (1.2 mg/kg, ip, dimethyl sulfoxide (DMSO as a placebo with equal volume 30 minutes before assessing the sedative and preanesthetic effects (induced sleep duration by ketamine, 40 mg/kg, ip and anxiolytic effects (using Elevated plus maze and (Rotarod test. Statistical analysis of the results obtained represent a significant increase in sleep time induced with ketamine and also a significant increase in the time the rats spent in open arms of maze with high and low doses of Lavandula stoechas herbal extract (p

Tests of the Aversive Summation Hypothesis in Rats: Effects of Restraint Stress on Consummatory Successive Negative Contrast and Extinction in the Barnes Maze

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Ortega, Leonardo A.; Prado-Rivera, Mayerli A.; Cardenas-Poveda, D. Carolina; McLinden, Kristina A.; Glueck, Amanda C.; Gutierrez, German; Lamprea, Marisol R.; Papini, Mauricio R.

2013-01-01

The present research explored the effects of restraint stress on two situations involving incentive downshift: consummatory successive negative contrast (cSNC) and extinction of escape behavior in the Barnes maze. First, Experiment 1 confirmed that the restraint stress procedure used in these experiments increased levels of circulating…

Spatial learning and psychomotor performance of C57BL/6 mice: age sensitivity and reliability of individual differences.

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de Fiebre, Nancyellen C; Sumien, Nathalie; Forster, Michael J; de Fiebre, Christopher M

2006-09-01

Two tests often used in aging research, the elevated path test and the Morris water maze test, were examined for their application to the study of brain aging in a large sample of C57BL/6JNia mice. Specifically, these studies assessed: (1) sensitivity to age and the degree of interrelatedness among different behavioral measures derived from these tests, (2) the effect of age on variation in the measurements, and (3) the reliability of individual differences in performance on the tests. Both tests detected age-related deficits in group performance that occurred independently of each other. However, analysis of data obtained on the Morris water maze test revealed three relatively independent components of cognitive performance. Performance in initial acquisition of spatial learning in the Morris maze was not highly correlated with performance during reversal learning (when mice were required to learn a new spatial location), whereas performance in both of those phases was independent of spatial performance assessed during a single probe trial administered at the end of acquisition training. Moreover, impaired performance during initial acquisition could be detected at an earlier age than impairments in reversal learning. There were modest but significant age-related increases in the variance of both elevated path test scores and in several measures of learning in the Morris maze test. Analysis of test scores of mice across repeated testing sessions confirmed reliability of the measurements obtained for cognitive and psychomotor function. Power calculations confirmed that there are sufficiently large age-related differences in elevated path test performance, relative to within age variability, to render this test useful for studies into the ability of an intervention to prevent or reverse age-related deficits in psychomotor performance. Power calculations indicated a need for larger sample sizes for detection of intervention effects on cognitive components of the

Elevated voltage level I{sub DDQ} failure testing of integrated circuits

Science.gov (United States)

Righter, A.W.

1996-05-21

Burn in testing of static CMOS IC`s is eliminated by I{sub DDQ} testing at elevated voltage levels. These voltage levels are at least 25% higher than the normal operating voltage for the IC but are below voltage levels that would cause damage to the chip. 4 figs.

Protective effect of maternal prenatal melatonin administration on rat pups born to mothers submitted to constant light during gestation

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C.D. Cisternas

2010-09-01

Full Text Available We studied the effects of adverse conditions such as constant light (LL on the circadian rhythm of malate (MDH, EC 1.1.1.37 and lactate (LDH, EC 1.1.1.27 dehydrogenase activities of the testes of male Wistar rats on postnatal day 28 (PN28, anxiety-like behavior (elevated plus-maze test at PN60 and sexual behavior at PN120. The rats were assigned to mother groups on day 10 of pregnancy: control (12-h light/dark, LL (light from day 10 to 21 of pregnancy, and LL+Mel (LL and sc injection to the mothers of a daily dose of melatonin, 1 mg/kg body weight at circadian time 12, from day 17 to 21 of pregnancy. LL offspring did not show circadian rhythms of MDH (N = 62 and LDH (N = 63 activities (cosinor and ANOVA-LSD Fisher. They presented a 44.7% decrease in open-arm entries and a 67.9% decrease in time (plus-maze test, N = 15, P < 0.001, Mann-Whitney U-test and Kruskal-Wallis test, an increase in mounting (94.4%, intromission (94.5% and ejaculation (56.6% latencies (N = 12, P < 0.01, Mann-Whitney U-test and Kruskal-Wallis test and lower numbers of these events (61, 59 and 73%, respectively; P < 0.01, N = 12 compared to controls. The offspring of the LL+Mel group presented MDH and LDH circadian rhythms (P < 0.05, N = 50, cosinor and ANOVA-LSD Fisher, anxiety-like and sexual behaviors similar to control. These findings supported the importance of the melatonin signal and provide evidence for the protective effects of hormones on maternal programming during gestation. This protective action of melatonin is probably related to its entrainment capacity, favoring internal coupling of the fetal multioscillatory system.

Co-segregation of hyperactivity, active coping styles, and cognitive dysfunction in mice selectively bred for low levels of anxiety

OpenAIRE

Yen, Yi-Chun; Anderzhanova, Elmira; Bunck, Mirjam; Schuller, Julia; Landgraf, Rainer; Wotjak, Carsten T.

2013-01-01

We established mouse models of extremes in trait anxiety, which are based on selective breeding for low vs. normal vs. high open-arm exploration on the elevated plus-maze. Genetically selected low anxiety-related behavior (LAB) coincided with hyperactivity in the home cage. Given the fact that several psychiatric disorders such as schizophrenia, mania, and attention deficit hyperactivity disorder (ADHD) share hyperactivity symptom, we systematically examined LAB mice with respect to unique an...

3, 4-methylenedioximethamphetamin reverses anxiety induced by chronic mild stress

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Laura Andrea León A

2013-01-01

Full Text Available Here we report the effects of subchronic 3, 4 methylenedioximethamphetamine (MDMA on the elevated plusmaze, a widely used animal model of anxiety. Rats exposed to a mild chronic stress (MCS protocol received intracerebroventricular microinjections of the selective serotonin reuptake inhibitor (SSRI – fluoxetine (2.0 ug/ul or MDMA, (2.0 ug/ul for seven days. On the eighth day rats were tested in the elevated plus-maze. Our results showed that sub chronic MDMA interacted with MCS leading to a decrease in anxiety related behaviors including: percentage of open arms entries (F [2, 26] = 4.00; p = 0.031, time spent in the open arms (F [2, 26] = 3.656; p = 0.040 and time spent in the open arms extremities (F [2, 26] = 5.842; p = 0.008. These results suggest a potential effect of MDMA in the reversion of the emotional significance of aversive stimuli.

Protracted effects of juvenile stressor exposure are mitigated by access to palatable food.

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Jennifer Christine MacKay

Full Text Available Stressor experiences during the juvenile period may increase vulnerability to anxiety and depressive-like symptoms in adulthood. Stressors may also promote palatable feeding, possibly reflecting a form of self-medication. The current study investigated the short- and long-term consequences of a stressor applied during the juvenile period on anxiety- and depressive-like behavior measured by the elevated plus maze (EPM, social interaction and forced swim test (FST. Furthermore, the effects of stress on caloric intake, preference for a palatable food and indices of metabolic syndrome and obesity were assessed. Male Wistar rats exposed to 3 consecutive days of variable stressors on postnatal days (PD 27-29, displayed elevated anxiety-like behaviors as adults, which could be attenuated by consumption of a palatable high-fat diet. However, consumption of a palatable food in response to a stressor appeared to contribute to increased adiposity.

Dai-Kenchu-To, a Herbal Medicine, Attenuates Colorectal Distention-induced Visceromotor Responses in Rats.

Science.gov (United States)

Nakaya, Kumi; Nagura, Yohko; Hasegawa, Ryoko; Ito, Hitomi; Fukudo, Shin

2016-10-30

Dai-kenchu-to (DKT), a traditional Japanese herbal medicine, is known to increase gastrointestinal motility and improve ileal function. We tested our hypotheses that (1) pretreatment with DKT would block the colorectal distention-induced visceromotor response in rats, and (2) pretreatment with DKT would attenuate colorectal distention-induced adrenocorticotropic hormone (ACTH) release and anxiety-related behavior. Rats were pretreated with vehicle or DKT (300 mg/kg/5 mL, per os). Visceromotor responses were analyzed using electromyography in response to colorectal distention (10, 20, 40, 60, and 80 mmHg for 20 seconds at 3-minutes intervals). Anxiety-related behavior was measured during exposure to an elevated-plus maze after colorectal distention. Plasma ACTH and serum corticosterone levels were measured after exposure to the elevated-plus maze. Colorectal distention produced robust contractions of the abdominal musculature, graded according to stimulus intensity, in vehicle-treated rats. At 40, 60, and 80 mmHg of colorectal distention, the visceromotor responses of DKT-treated rats was significantly lower than that of vehicle-treated rats. At 80 mmHg, the amplitude was suppressed to approximately one-third in DKT-treated rats, compared with that in vehicle-treated rats. Smooth muscle compliance and the velocity of accommodation to 60 mmHg of stretching did not significantly differ between the vehicle-treated and DKT-treated rats. Similarly, the DKT did not influence colorectal distention-induced ACTH release, corticosterone levels, or anxiety-related behavior in rats. Our results suggest that DKT attenuates the colorectal distention-induced visceromotor responses, without increasing smooth muscle compliance, ACTH release or anxiety-related behavior in rats.

Effect of diet on brain metabolites and behavior in spontaneously hypertensive rats.

Science.gov (United States)

Liso Navarro, Ana A; Sikoglu, Elif M; Heinze, Cailin R; Rogan, Ryan C; Russell, Vivienne A; King, Jean A; Moore, Constance M

2014-08-15

Attention-deficit hyperactivity disorder (ADHD) is a heterogeneous psychiatric disorder affecting 5-10% of children. One of the suggested mechanisms underlying the pathophysiology of ADHD is insufficient energy supply to neurons. Here, we investigated the role of omega 3 fatty acids in altering neural energy metabolism and behavior of spontaneously hypertensive rats (SHR), which is an animal model of ADHD. To this end, we employed Proton Magnetic Resonance Spectroscopy ((1)H MRS) to evaluate changes in brain neurochemistry in the SHR following consumption of one of three experimental diets (starting PND 21): fish oil enriched (FOE), regular (RD) and animal fat enriched (AFE) diet. Behavioral tests were performed to evaluate differences in locomotor activity and risk-taking behavior (starting PND 44). Comparison of frontal lobe metabolites showed that increased amounts of omega 3 fatty acids decreased total Creatine levels (tCr), but did not change Glutamate (Glu), total N-Acetylaspartate (tNAA), Lactate (Lac), Choline (Cho) or Inositol (Ino) levels. Although behavior was not significantly affected by different diets, significant correlations were observed between brain metabolites and behavior in the open field and elevated plus maze. SHR with higher levels of brain tCr and Glu exhibited greater hyperactivity in a familiar environment. On the other hand, risk-taking exploration of the elevated plus maze's open arms correlated negatively with forebrain tNAA and Lac levels. These findings support the possible alteration in energy metabolites in ADHD, correlating with hyperactivity in the animal model. The data also suggest that omega 3 fatty acids alter brain energy and phospholipid metabolism. Copyright © 2014 Elsevier B.V. All rights reserved.

Kinoscope: An Open-Source Computer Program for Behavioral Pharmacologists

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Nikolaos Kokras

2017-05-01

Full Text Available Behavioral analysis in preclinical neuropsychopharmacology relies on the accurate measurement of animal behavior. Several excellent solutions for computer-assisted behavioral analysis are available for specialized behavioral laboratories wishing to invest significant resources. Herein, we present an open source straightforward software solution aiming at the rapid and easy introduction to an experimental workflow, and at the improvement of training staff members in a better and more reproducible manual scoring of behavioral experiments with the use of visual aids-maps. Currently the program readily supports the Forced Swim Test, Novel Object Recognition test and the Elevated Plus maze test, but with minor modifications can be used for scoring virtually any behavioral test. Additional modules, with predefined templates and scoring parameters, are continuously added. Importantly, the prominent use of visual maps has been shown to improve, in a student-engaging manner, the training and auditing of scoring in behavioral rodent experiments.

Medial Entorhinal Grid Cells and Head Direction Cells Rotate with a T-Maze More Often During Less Recently Experienced Rotations

Science.gov (United States)

Gupta, Kishan; Beer, Nathan J.; Keller, Lauren A.; Hasselmo, Michael E.

2014-01-01

Prior studies of head direction (HD) cells indicate strong landmark control over the preferred firing direction of these cells, with few studies exhibiting shifts away from local reference frames over time. We recorded spiking activity of grid and HD cells in the medial entorhinal cortex of rats, testing correlations of local environmental cues with the spatial tuning curves of these cells' firing fields as animals performed continuous spatial alternation on a T-maze that shared the boundaries of an open-field arena. The environment was rotated into configurations the animal had either seen or not seen in the past recording week. Tuning curves of both cell types demonstrated commensurate shifts of tuning with T-maze rotations during less recent rotations, more so than recent rotations. This strongly suggests that animals are shifting their reference frame away from the local environmental cues over time, learning to use a different reference frame more likely reliant on distal or idiothetic cues. In addition, grid fields demonstrated varying levels of “fragmentation” on the T-maze. The propensity for fragmentation does not depend on grid spacing and grid score, nor animal trajectory, indicating the cognitive treatment of environmental subcompartments is likely driven by task demands. PMID:23382518

Effects of 1.8 GHz Radiofrequency Fields on the Emotional Behavior and Spatial Memory of Adolescent Mice

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Jun-Ping Zhang

2017-11-01

Full Text Available The increasing use of mobile phones by teenagers has raised concern about the cognitive effects of radiofrequency (RF fields. In this study, we investigated the effects of 4-week exposure to a 1.8 GHz RF field on the emotional behavior and spatial memory of adolescent male mice. Anxiety-like behavior was evaluated by open field test (OFT and elevated plus maze (EPM test, while depression-like behavior was evaluated by sucrose preference test (SPT, tail suspension test (TST and forced swim test (FST. The spatial learning and memory ability were evaluated by Morris water maze (MWM experiments. The levels of amino acid neurotransmitters were determined by liquid chromatography-mass spectrometry (LC-MS. The histology of the brain was examined by hematoxylin-eosin (HE staining. It was found that the depression-like behavior, spatial memory ability and histology of the brain did not change obviously after RF exposure. However, the anxiety-like behavior increased in mice, while, the levels of γ-aminobutyric acid (GABA and aspartic acid (Asp in cortex and hippocampus significantly decreased after RF exposure. These data suggested that RF exposure under these conditions do not affect the depression-like behavior, spatial memory and brain histology in adolescent male mice, but it may however increase the level of anxiety, and GABA and Asp were probably involved in this effect.

A Wireless EEG Recording Method for Rat Use inside the Water Maze.

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Richard C Pinnell

Full Text Available With the continued miniaturisation of portable embedded systems, wireless EEG recording techniques are becoming increasingly prevalent in animal behavioural research. However, in spite of their versatility and portability, they have seldom been used inside water-maze tasks designed for rats. As such, a novel 3D printed implant and waterproof connector is presented, which can facilitate wireless water-maze EEG recordings in freely-moving rats, using a commercial wireless recording system (W32; Multichannel Systems. As well as waterproofing the wireless system, battery, and electrode connector, the implant serves to reduce movement-related artefacts by redistributing movement-related forces away from the electrode connector. This implant/connector was able to successfully record high-quality LFP in the hippocampo-striatal brain regions of rats as they undertook a procedural-learning variant of the double-H water-maze task. Notably, there were no significant performance deficits through its use when compared with a control group across a number of metrics including number of errors and speed of task completion. Taken together, this method can expand the range of measurements that are currently possible in this diverse area of behavioural neuroscience, whilst paving the way for integration with more complex behaviours.

Behavioral Characterization of the Effects of Cannabis Smoke and Anandamide in Rats.

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Adriaan W Bruijnzeel

Full Text Available Cannabis is the most widely used illicit drug in the world. Delta-9-tetrahydrocannabinol (Δ9-THC is the main psychoactive component of cannabis and its effects have been well-studied. However, cannabis contains many other cannabinoids that affect brain function. Therefore, these studies investigated the effect of cannabis smoke exposure on locomotor activity, rearing, anxiety-like behavior, and the development of dependence in rats. It was also investigated if cannabis smoke exposure leads to tolerance to the locomotor-suppressant effects of the endogenous cannabinoid anandamide. Cannabis smoke was generated by burning 5.7% Δ9-THC cannabis cigarettes in a smoking machine. The effect of cannabis smoke on the behavior of rats in a small and large open field and an elevated plus maze was evaluated. Cannabis smoke exposure induced a brief increase in locomotor activity followed by a prolonged decrease in locomotor activity and rearing in the 30-min small open field test. The cannabinoid receptor type 1 (CB1 receptor antagonist rimonabant increased locomotor activity and prevented the smoke-induced decrease in rearing. Smoke exposure also increased locomotor activity in the 5-min large open field test and the elevated plus maze test. The smoke exposed rats spent more time in the center zone of the large open field, which is indicative of a decrease in anxiety-like behavior. A high dose of anandamide decreased locomotor activity and rearing in the small open field and this was not prevented by rimonabant or pre-exposure to cannabis smoke. Serum Δ9-THC levels were 225 ng/ml after smoke exposure, which is similar to levels in humans after smoking cannabis. Exposure to cannabis smoke led to dependence as indicated by more rimonabant-precipitated somatic withdrawal signs in the cannabis smoke exposed rats than in the air-control rats. In conclusion, chronic cannabis smoke exposure in rats leads to clinically relevant Δ9-THC levels, dependence, and has

Polymethoxyflavones from Nicotiana plumbaginifolia (Solanaceae Exert Antinociceptive and Neuropharmacological Effects in Mice

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Md. Shafiullah Shajib

2018-02-01

Full Text Available Polymethoxylavones (PMFs are known to exhibit significant anti-inflammatory and neuroprotective properties. Nicotiana plumbaginifolia, an annual Bangladeshi herb, is rich in polymethoxyflavones that possess significant analgesic and anxiolytic activities. The present study aimed to determine the antinociceptive and neuropharmacological activities of polyoxygenated flavonoids namely- 3,3′,5,6,7,8-hexamethoxy-4′,5′-methylenedioxyflavone (1, 3,3′,4′,5′,5,6,7,8-octamethoxyflavone (exoticin (2, 6,7,4′,5′-dimethylenedioxy-3,5,3′-trimethoxyflavone (3, and 3,3′,4′,5,5′,8-hexamethoxy-6,7-methylenedioxyflavone (4, isolated and identified from N. plumbaginifolia. Antinociceptive activity was assessed using the acetic-acid induced writhing, hot plate, tail immersion, formalin and carrageenan-induced paw edema tests, whereas neuropharmacological effects were evaluated in the hole cross, open field and elevated plus maze test. Oral treatment of compounds 1, 3, and 4 (12.5–25 mg/kg b.w. exhibited dose-dependent and significant (p < 0.01 antinociceptive activity in the acetic-acid, formalin, carrageenan, and thermal (hot plate-induced pain models. The association of ATP-sensitive K+ channel and opioid systems in their antinociceptive effect was obvious from the antagonist effect of glibenclamide and naloxone, respectively. These findings suggested central and peripheral antinociceptive activities of the compounds. Compound 1, 3, and 4 (12.5 mg/kg b.w. demonstrated significant (p < 0.05 anxiolytic-like activity in the elevated plus-maze test, while the involvement of GABAA receptor in the action of compound 3 and 4 was evident from the reversal effects of flumazenil. In addition, compounds 1 and 4 (12.5–25 mg/kg b.w exhibited anxiolytic activity without altering the locomotor responses. The present study suggested that the polymethoxyflavones (1–4 from N. Plumbaginifolia could be considered as suitable candidates for the development

Gypenosides ameliorate memory deficits in MPTP-lesioned mouse model of Parkinson's disease treated with L-DOPA.

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Zhao, Ting Ting; Kim, Kyung Sook; Shin, Keon Sung; Park, Hyun Jin; Kim, Hyun Jeong; Lee, Kyung Eun; Lee, Myung Koo

2017-09-06

Previous studies have revealed that gypenosides (GPS) improve the symptoms of anxiety disorders in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned rat model of Parkinson's disease (PD). The present study aimed to investigate the effects of GPS on memory deficits in an MPTP-lesioned mouse model of PD treated with L-3,4-dihydroxyphenylalanine (L-DOPA). MPTP (30 mg/kg/day, 5 days)-lesioned mice were treated with GPS (50 mg/kg) and/or L-DOPA (10 and 25 mg/kg) for 21 days. After the final treatments, behavioral changes were assessed in all mice using passive avoidance and elevated plus-maze tests. We then evaluated the biochemical influences of GPS treatment on levels of tyrosine hydroxylase (TH), dopamine, N-methyl-D-aspartate (NMDA) receptors, extracellular signal-regulated kinase (ERK1/2), and cyclic AMP-response element binding protein (CREB) phosphorylation. MPTP-lesioned mice exhibited deficits associated with habit learning and spatial memory, which were further aggravated by treatment with L-DOPA (25 mg/kg). However, treatment with GPS (50 mg/kg) ameliorated memory deficits. Treatment with GPS (50 mg/kg) also improved L-DOPA (25 mg/kg)-treated MPTP lesion-induced decreases in retention latency on the passive avoidance test, as well as levels of TH-immunopositive cells and dopamine in the substantia nigra and striatum. GPS treatment also attenuated increases in retention transfer latency on the elevated plus-maze test and in NMDA receptor expression, as well as decreases in the phosphorylation of ERK1/2 and CREB in the hippocampus. Treatment with L-DOPA (10 mg/kg) also ameliorated deficits in habit learning and spatial memory in MPTP-lesioned mice, and this effect was further enhanced by treatment with GPS (50 mg/kg). GPS ameliorate deficits in habit learning and spatial memory by modulating the dopaminergic neuronal and N-methyl-D-aspartate receptor-mediated signaling systems in MPTP-lesioned mice treated with L-DOPA. GPS may serve as an adjuvant

Corticotropin Releasing Factor in the Bed Nucleus of the Stria Terminalis in Socially Defeated and Non-stressed Mice with a History of Chronic Alcohol Intake

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Lucas Albrechet-Souza

2017-10-01

Full Text Available Stress exposure has been identified as one risk factor for alcohol abuse that may facilitate the transition from social or regulated use to the development of alcohol dependence. Preclinical studies have shown that dysregulation of the corticotropin releasing factor (CRF neurotransmission has been implicated in stress-related psychopathologies such as depression and anxiety, and may affect alcohol consumption. The bed nucleus of the stria terminalis (BNST contains CRF-producing neurons which seem to be sensitive to stress. In this study, adult male C57BL/6 mice previously defeated in resident-intruder confrontations were evaluated in the elevated plus-maze and tail suspension test. Mice were also tested for sweet solution intake before and after social stress. After having had continuous access to ethanol (20% weight/volume for 4 weeks, control and stressed mice had CRF type 1 (CRFR1 or type 2 (CRFR2 receptor antagonists infused into the BNST and then had access to ethanol for 24 h. In separate cohorts of control and stressed mice, we assessed mRNA levels of BNST CRF, CRFR1 and CRFR2. Stressed mice increased their intake of sweet solution after ten sessions of social defeat and showed reduced activity in the open arms of the elevated plus-maze. When tested for ethanol consumption, stressed mice persistently drank significantly more than controls during the 4 weeks of access. Also, social stress induced higher BNST CRF mRNA levels. The selective blockade of BNST CRFR1 with CP376,395 effectively reduced alcohol drinking in non-stressed mice, whereas the selective CRFR2 antagonist astressin2B produced a dose-dependent increase in ethanol consumption in both non-stressed controls and stressed mice. The 10-day episodic defeat stress used here elicited anxiety- but not depressive-like behaviors, and promoted an increase in ethanol drinking. CRF-CRFR1 signaling in the BNST seems to underlie ethanol intake in non-stressed mice, whereas CRFR2 modulates

Corticotropin Releasing Factor in the Bed Nucleus of the Stria Terminalis in Socially Defeated and Non-stressed Mice with a History of Chronic Alcohol Intake.

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Albrechet-Souza, Lucas; Viola, Thiago W; Grassi-Oliveira, Rodrigo; Miczek, Klaus A; de Almeida, Rosa M M

2017-01-01

Stress exposure has been identified as one risk factor for alcohol abuse that may facilitate the transition from social or regulated use to the development of alcohol dependence. Preclinical studies have shown that dysregulation of the corticotropin releasing factor (CRF) neurotransmission has been implicated in stress-related psychopathologies such as depression and anxiety, and may affect alcohol consumption. The bed nucleus of the stria terminalis (BNST) contains CRF-producing neurons which seem to be sensitive to stress. In this study, adult male C57BL/6 mice previously defeated in resident-intruder confrontations were evaluated in the elevated plus-maze and tail suspension test. Mice were also tested for sweet solution intake before and after social stress. After having had continuous access to ethanol (20% weight/volume) for 4 weeks, control and stressed mice had CRF type 1 (CRFR1) or type 2 (CRFR2) receptor antagonists infused into the BNST and then had access to ethanol for 24 h. In separate cohorts of control and stressed mice, we assessed mRNA levels of BNST CRF, CRFR1 and CRFR2 . Stressed mice increased their intake of sweet solution after ten sessions of social defeat and showed reduced activity in the open arms of the elevated plus-maze. When tested for ethanol consumption, stressed mice persistently drank significantly more than controls during the 4 weeks of access. Also, social stress induced higher BNST CRF mRNA levels. The selective blockade of BNST CRFR1 with CP376,395 effectively reduced alcohol drinking in non-stressed mice, whereas the selective CRFR2 antagonist astressin2B produced a dose-dependent increase in ethanol consumption in both non-stressed controls and stressed mice. The 10-day episodic defeat stress used here elicited anxiety- but not depressive-like behaviors, and promoted an increase in ethanol drinking. CRF-CRFR1 signaling in the BNST seems to underlie ethanol intake in non-stressed mice, whereas CRFR2 modulates alcohol

Differential roles for neuropeptide Y Y1 and Y5 receptors in anxiety and sedation

DEFF Research Database (Denmark)

Sørensen, Gunnar; Lindberg, Camilla; Wörtwein, Gitta

2004-01-01

PP(1-7),NPY(19-23),Ala(31),Aib(32),Gln(34)]hPP) in the elevated plus maze and open field tests. As with NPY, the Y1 agonist had a dose-dependent anxiolytic-like effect in both behavioral tests. In contrast to NPY, which caused significant sedation in the open field test, the Y1 agonist was without...... sedative effect. The Y2 agonist showed neither anxiolytic-like nor sedative effects. The Y5 agonist showed anxiolytic-like activity in both behavioral tests and caused sedation in the same dose range as NPY in the open field test. These results indicate that anxiolytic-like effects of i...... NPY receptors in anxiety and sedation remains a possibility. In the present study, we addressed this issue by testing the effects of intracerebroventricular (i.c.v.) injection of NPY as well as specific receptor agonists for the Y1 receptor ([D-His(26)]NPY), Y2 receptor (C2-NPY), and Y5 receptor ([c...

Comparative study of nasoalveolar molding methods: nasal elevator plus DynaCleft® versus NAM-Grayson in patients with complete unilateral cleft lip and palate.

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Monasterio, Luis; Ford, Alison; Gutiérrez, Carolina; Tastets, María Eugenia; García, Jacqueline

2013-09-01

Objective : To compare nasoalveolar molding (NAM) effect employing a nasal elevator plus DynaCleft® and NAM-Grayson system in patients with complete unilateral cleft lip and palate. Method : Prospective study in two groups. Group A included 20 consecutive patients treated with DynaCleft® and a nasal elevator before lip surgery. Group B included 20 patients treated with NAM-Grayson system. Maxillary casts and standard view photographs were done before and after treatment. Columella deviation angle, soft tissue distance of the cleft, intercommisural distance, and nostril height and width were traced and measured on the printed photos; a ratio was obtained and compared before and after treatment. Cleft width, anterior width, and anteroposterior distances were measured on the maxillary cast. Results : Group A began treatment at an average age of 14.3 days and group B at an average age of 16.9 days; no complications were observed. For group A, the initial average alveolar cleft within the cast was 10.7 mm, and after treatment it was 6.6 mm. For group B, pretreatment width was 11.2 mm, and after treatment it was 5.9 mm. No differences were found on the anterior and posterior width, and A-P distance of both groups. The initial mean columellar angle in group A was 38.1°, and after treatment it was 61.5°; for group B the initial mean columellar angle was 33.6°, and after treatment it was 59.5°. Results of Mann-Whitney U and Student's t tests showed no differences (P > .05). Width and height dimensions of the nostril showed minor differences. Conclusions : Both methods significantly reduced the cleft width and improved the nasal asymmetry. Our findings show that both methods produced similar results.

LIBRJMCMC: AN OPEN-SOURCE GENERIC C&plus;&plus; LIBRARY FOR STOCHASTIC OPTIMIZATION

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M. Brédif

2012-07-01

Full Text Available The librjmcmc is an open source C&plus;&plus; library that solves optimization problems using a stochastic framework. The library is primarily intended for but not limited to research purposes in computer vision, photogrammetry and remote sensing, as it has initially been developed in the context of extracting building footprints from digital elevation models using a marked point process of rectangles. It has been designed to be both highly modular and extensible, and have computational times comparable to a code specifically designed for a particular application, thanks to the powerful paradigms of metaprogramming and generic programming. The proposed stochastic optimization is built on the coupling of a stochastic Reversible-Jump Markov Chain Monte Carlo (RJMCMC sampler and a simulated annealing relaxation. This framework allows, with theoretical guarantees, the optimization of an unrestricted objective function without requiring any initial solution. The modularity of our library allows the processing of any kind of input data, whether they are 1D signals (e.g. LiDAR or SAR waveforms, 2D images, 3D point clouds... The library user has just to define a few modules describing its domain specific context: the encoding of a configuration (e.g. its object type in a marked point process context, reversible jump kernels (e.g. birth, death, modifications..., the optimized energies (e.g. data and regularization terms and the probabilized search space given by the reference process. Similar to this extensibility in the application domain, concepts are clearly and orthogonally separated such that it is straightforward to customize the convergence test, the temperature schedule, or to add visitors enabling visual feedback during the optimization. The library offers dedicated modules for marked point processes, allowing the user to optimize a Maximum A Posteriori (MAP criterion with an image data term energy on a marked point process of rectangles.

Phytochemical analysis, antioxidant, antistress, and nootropic activities of aqueous and methanolic seed extracts of ladies finger (Abelmoschus esculentus L.) in mice.

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Doreddula, Sathish Kumar; Bonam, Srinivasa Reddy; Gaddam, Durga Prasad; Desu, Brahma Srinivasa Rao; Ramarao, Nadendla; Pandy, Vijayapandi

2014-01-01

Abelmoschus esculentus L. (ladies finger, okra) is a well-known tropical vegetable, widely planted from Africa to Asia and from South Europe to America. In the present study, we investigated the in vitro antioxidant capacity and in vivo protective effect of the aqueous and methanolic seed extracts of Abelmoschus esculentus against scopolamine-induced cognitive impairment using passive avoidance task and acute restraining stress-induced behavioural and biochemical changes using elevated plus maze (EPM) and forced swimming test (FST) in mice. Our results demonstrated that the pretreatment of mice with aqueous and methanolic seed extracts of Abelmoschus esculentus (200 mg/kg, p.o.) for seven days significantly (P nootropic activities which promisingly support the medicinal values of ladies finger as a vegetable.

Standard test methods for elevated temperature tension tests of metallic materials

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American Society for Testing and Materials. Philadelphia

2009-01-01

1.1 These test methods cover procedure and equipment for the determination of tensile strength, yield strength, elongation, and reduction of area of metallic materials at elevated temperatures. 1.2 Determination of modulus of elasticity and proportional limit are not included. 1.3 Tension tests under conditions of rapid heating or rapid strain rates are not included. 1.4 The values stated in inch-pound units are to be regarded as standard. The values given in parentheses are mathematical conversions to SI units that are provided for information only and are not considered standard. 1.5 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety and health practices and determine the applicability of regulatory limitations prior to use.

SENSOR&plus;&plus;: Simulation of Remote Sensing Systems from Visible to Thermal Infrared

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Paproth, C.; Schlüßler, E.; Scherbaum, P.; Börner, A.

2012-07-01

During the development process of a remote sensing system, the optimization and the verification of the sensor system are important tasks. To support these tasks, the simulation of the sensor and its output is valuable. This enables the developers to test algorithms, estimate errors, and evaluate the capabilities of the whole sensor system before the final remote sensing system is available and produces real data. The presented simulation concept, SENSOR&plus;&plus;, consists of three parts. The first part is the geometric simulation which calculates where the sensor looks at by using a ray tracing algorithm. This also determines whether the observed part of the scene is shadowed or not. The second part describes the radiometry and results in the spectral at-sensor radiance from the visible spectrum to the thermal infrared according to the simulated sensor type. In the case of earth remote sensing, it also includes a model of the radiative transfer through the atmosphere. The final part uses the at-sensor radiance to generate digital images by using an optical and an electronic sensor model. Using SENSOR&plus;&plus; for an optimization requires the additional application of task-specific data processing algorithms. The principle of the simulation approach is explained, all relevant concepts of SENSOR&plus;&plus; are discussed, and first examples of its use are given, for example a camera simulation for a moon lander. Finally, the verification of SENSOR&plus;&plus; is demonstrated.

Adolescent fluoxetine exposure produces enduring, sex-specific alterations of visual discrimination and attention in rats.

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LaRoche, Ronee B; Morgan, Russell E

2007-01-01

Over the past two decades the use of selective serotonin reuptake inhibitors (SSRIs) to treat behavioral disorders in children has grown rapidly, despite little evidence regarding the safety and efficacy of these drugs for use in children. Utilizing a rat model, this study investigated whether post-weaning exposure to a prototype SSRI, fluoxetine (FLX), influenced performance on visual tasks designed to measure discrimination learning, sustained attention, inhibitory control, and reaction time. Additionally, sex differences in response to varying doses of fluoxetine were examined. In Experiment 1, female rats were administered (P.O.) fluoxetine (10 mg/kg ) or vehicle (apple juice) from PND 25 thru PND 49. After a 14 day washout period, subjects were trained to perform a simultaneous visual discrimination task. Subjects were then tested for 20 sessions on a visual attention task that consisted of varied stimulus delays (0, 3, 6, or 9 s) and cue durations (200, 400, or 700 ms). In Experiment 2, both male and female Long-Evans rats (24 F, 24 M) were administered fluoxetine (0, 5, 10, or 15 mg/kg) then tested in the same visual tasks used in Experiment 1, with the addition of open-field and elevated plus-maze testing. Few FLX-related differences were seen in the visual discrimination, open field, or plus-maze tasks. However, results from the visual attention task indicated a dose-dependent reduction in the performance of fluoxetine-treated males, whereas fluoxetine-treated females tended to improve over baseline. These findings indicate that enduring, behaviorally-relevant alterations of the CNS can occur following pharmacological manipulation of the serotonin system during postnatal development.

Preventive effects of ginsenoside Rg1 on post-traumatic stress disorder (PTSD)-like behavior in male C57/B6 mice.

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Wang, Zhongli; Zhu, Kexuan; Chen, Lin; Ou Yang, Liufeng; Huang, Yufang; Zhao, Yunan

2015-09-25

We investigated the preventive effects of Rg1 on a model of mouse post-traumatic stress disorder (PTSD) induced by electric shock combined with situation reminder and explored the underlying mechanism. In the experiment, before the PTSD animal model was developed, Rg1 (10, 5, and 2.5mg/kg) was orally administered for one week. After the animal model was established, PTSD-like behavior was observed using elevated plus maze, black and light box, and open field tests. One hour after the behavior test, all mice were sacrificed, and then serum corticosterone (CORT) and hypothalamus corticotrophin-releasing hormone (CRH) assays were performed. Results showed that Rg1 (5mg/kg) treatments relieved PTSD-like behavior by altering elevated serum corticosterone and hypothalamus CRH levels. By contrast, fluoxetine (3mg/kg) treatment reversed the behavior changes and had no effect on increased CORT and CRH levels. These findings confirmed the preventive effect of Rg1 in PTSD model. Decreasing CORT and CRH levels may be one of the underlying mechanisms. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Learning to remember: Cognitive training-induced attenuation of age-related memory decline depends on sex and cognitive demand, and can transfer to untrained cognitive domains

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Talboom, Joshua S.; West, Stephen G.; Engler-Chiurazzi, Elizabeth B.; Enders, Craig K.; Crain, Ian; Bimonte-Nelson, Heather A.

2014-01-01

Aging is associated with progressive changes in learning and memory. A potential approach to attenuate age-related cognitive decline is cognitive training. In this study, adult male and female rats were given either repeated exposure to a T-maze, or no exposure to any maze, and then tested on a final battery of cognitive tasks. Two groups of each sex were tested from 6-18 months old on the same T-maze; one group received a version testing spatial reference memory, and the other group received only the procedural testing components with minimal cognitive demand. Groups three and four of each sex had no maze exposure until the final battery, and were comprised of aged or young rats. The final maze battery included the practiced T-maze plus two novel tasks, one with a similar, and one with a different, memory type to the practice task. The fifth group of each sex was not maze tested, serving as an aged control for the effects of maze testing on neurotrophin protein levels in cognitive brain regions. Results showed that adult intermittent cognitive training enhanced performance on the practice task when aged in both sexes, that cognitive training benefits transferred to novel tasks only in females, and that cognitive demand was necessary for these effects since rats receiving only the procedural testing components showed no improvement on the final maze battery. Further, for both sexes, rats that showed faster learning when young demonstrated better memory when aged. Age-related increases in neurotrophin concentrations in several brain regions were revealed, which was related to performance on the training task only in females. This longitudinal study supports the tenet that cognitive training can help one remember later in life, with broader enhancements and associations with neurotrophins in females. PMID:25104561

Gastrodia elata Bl. Attenuated learning deficits induced by forced-swimming stress in the inhibitory avoidance task and Morris water maze.

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Chen, Pei-Ju; Liang, Keng-Chen; Lin, Hui-Chen; Hsieh, Ching-Liang; Su, Kuan-Pin; Hung, Mei-Chu; Sheen, Lee-Yan

2011-06-01

This study adopted the forced-swimming paradigm to induce depressive symptoms in rats and evaluated the effects on learning and memory processing. Furthermore, the effects of the water extract of Gastrodia elata Bl., a well-known Chinese traditional medicine, on amnesia in rats subjected to the forced-swimming procedure were studied. Rats were subjected to the forced-swimming procedure, and the inhibitory avoidance task and Morris water maze were used to assess learning and memory performance. The acquisition of the two tasks was mostly impaired after the 15-minute forced-swimming procedure. Administration of the water extract of G. elata Bl. for 21 consecutive days at a dosage of 0.5 or 1.0 g/kg of body weight significantly improved retention in the inhibitory avoidance test, and the lower dose showed a better effect than the higher one and the antidepressant fluoxetine (18 mg/kg of body weight). In the Morris water maze, the lower dose of the water extract of G. elata Bl. significantly improved retention by shortening escape latency in the first test session and increasing the time in searching the target zone during the probe test. These findings suggest that water extracts of G. elata Bl. ameliorate the learning and memory deficits induced by forced swimming.

Use of maze in cyclotron hoppers

International Nuclear Information System (INIS)

Fernandes, Fernando A.; Alves, Juliano S.; Fochesatto, Cintia; Cerioli, Luciane; Borges, Joao Alfredo; Gonzalez, Delfin; Silva, Daniel C.

2013-01-01

Introduction: the increasing number of cyclotrons in Brazil due to constitutional amendment 49 /06 that enabled the production of radiopharmaceuticals with a short half - life by private companies. The radionuclides used for PET - CT require production centers near or within the diagnostic centers. In order to minimize maintenance and operating risks, gaining efficiency, our facility was the first in Brazil to use the access to a cyclotron bunker via maze, rather than armored door stopper type. Materials: the design calculations were based on the Monte Carlo method (MCNP5 - Monte Carlo N-Particletransportcode version 5). At the ends of the labyrinth are installed a door of polyethylene, for thermalization of neutrons, and other of wood for limiting access. Both legs of the maze have wall thickness of 100cm. In inspection Brazilian CNEN realize measures of dose rate for neutrons and gamma 9 points: 7 around the bunker, 1 over the bunker and 1 in the exhaust with the cyclotron operating with maximum load, double beam of 50uA for 2 hours. After commissioning were carried out around the bunker, the following measures: cumulative dose in three months with dosimeters for neutron rate dose with a gas proportional detector type filled with 3 He and polyethylene neutron moderator and dose rate with a Geiger - Mueller detector for gamma radiation. Readings with neutron detectors were classified as background radiation and dose rates were always below the limits established in standard EN 3.01, and the calculation of the predicted regardless of the intensity of irradiation inside the bunker. Conclusion: the use of labyrinths as a way to access the bunkers cyclotron has been shown to be effective as the radiation shielding and efficient by allowing quick and easy access, virtually eliminating the maintenance

Declarative virtual water maze learning and emotional fear conditioning in primary insomnia.

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Kuhn, Marion; Hertenstein, Elisabeth; Feige, Bernd; Landmann, Nina; Spiegelhalder, Kai; Baglioni, Chiara; Hemmerling, Johanna; Durand, Diana; Frase, Lukas; Klöppel, Stefan; Riemann, Dieter; Nissen, Christoph

2018-05-02

Healthy sleep restores the brain's ability to adapt to novel input through memory formation based on activity-dependent refinements of the strength of neural transmission across synapses (synaptic plasticity). In line with this framework, patients with primary insomnia often report subjective memory impairment. However, investigations of memory performance did not produce conclusive results. The aim of this study was to further investigate memory performance in patients with primary insomnia in comparison to healthy controls, using two well-characterized learning tasks, a declarative virtual water maze task and emotional fear conditioning. Twenty patients with primary insomnia according to DSM-IV criteria (17 females, three males, 43.5 ± 13.0 years) and 20 good sleeper controls (17 females, three males, 41.7 ± 12.8 years) were investigated in a parallel-group study. All participants completed a hippocampus-dependent virtual Morris water maze task and amygdala-dependent classical fear conditioning. Patients with insomnia showed significantly delayed memory acquisition in the virtual water maze task, but no significant difference in fear acquisition compared with controls. These findings are consistent with the notion that memory processes that emerge from synaptic refinements in a hippocampal-neocortical network are particularly sensitive to chronic disruptions of sleep, while those in a basic emotional amygdala-dependent network may be more resilient. © 2018 European Sleep Research Society.

Learning and memory enhancing activity of Ficus carica (Fig: An experimental study in rats

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Meera Sumanth

2014-01-01

Full Text Available Objective: The study aimed to assess the learning and memory enhancing activity of the ethanolic fruit extract of Ficus carica in rats using elevated plus maze (EPM, Hebb-William maze (HWM and Morris water maze (MWM. Materials and Methods: Wistar rats (100-150 g of either sex, were divided into 5 groups (n = 6. Group I (control animals received vehicle, Group II (scopolamine control animals received scopolamine (0.4 mg/kg i.p, Groups III and IV animals received ethanolic fruit extract of F. carica (200 mg/kg and 400 mg/kg p.o and Group V animals received piracetam (400 mg/kg i.p for 27 days. The rats of Groups III-V were injected with a single dose of scopolamine (0.4 mg/kg i.p on 19 th and 27 th day. Assessment of transfer latency (TL, time taken to reach reward chamber (TRC and swim latency (SL was done on 19 th and 27 th day using EPM, HWM and MWM, respectively. The data was analyzed by one-way Analysis of Variance followed by Dunnett′s test. P ≤ 0.05 was considered to be significant. Results: Ethanolic fruit extract of F. carica decreased TL, TRC and SL in comparison to scopolamine treated rats. Conclusion: The fruit of F. carica enhanced learning and memory activity.

Neudesin is involved in anxiety behavior: structural and neurochemical correlates

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Ashley eNovais

2013-09-01

Full Text Available Neudesin (also known as neuron derived neurotrophic factor, Nenf is a scarcely studied putative non-canonical neurotrophic factor. In order to understand its function in the brain, we performed an extensive behavioral characterization (motor, emotional and cognitive dimensions of neudesin-null mice. The absence of neudesin leads to an anxious-like behavior as assessed in the elevated plus maze, light/dark box and novelty suppressed feeding tests, but not in the acoustic startle test. This anxious phenotype is associated with reduced dopaminergic input and impoverished dendritic arborizations in the dentate gyrus granule neurons of the ventral hippocampus. Interestingly, shorter dendrites are also observed in the bed nucleus of the stria terminalis (BNST of neudesin-null mice. These findings lead us to suggest that neudesin is a novel relevant player in the maintenance of the anxiety circuitry.

The effect of cage size on reproductive performance and behavior of C57BL/6 mice.

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Whitaker, Julia; Moy, Sheryl S; Saville, Benjamin R; Godfrey, Virginia; Nielsen, Judith; Bellinger, Dwight; Bradfield, John

2007-11-01

Scientific research has yet to conclusively determine the optimal cage size for mice. The authors examined the effect of cage size on mouse breeding performance and on offspring behavior, which can serve as indications of overall well-being. They housed breeding trios of C57BL/6Tac mice in standard or large individually ventilated cages and measured four reproductive parameters: litter size; litter survival to weaning age; average pup weight at 7, 14 and 21 days; and the number of days between litter births. They investigated the behavior of a subset of male and female pups from parents housed in cages of each size in the elevated plus maze test, the open field assay and the acoustic startle test. Cage size had no significant effect on any of the reproductive parameters measured and few or inconsistent effects on behavior in weaned pups.

Effects of Mimosa pudica L. leaves extract on anxiety, depression and memory

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Ganesh Patro

2016-11-01

Full Text Available Objective: The present study was carried out to investigate the neuropharmacological activities of ethyl acetate extract of Mimosa pudica (EAMP leaves on anxiety, depression and memory in a mouse model. Materials and Methods: Anti-anxiety potential of EAMP was evaluated by elevated plus maze (EPM, light-dark box (LDB and social interaction (SI tests in mice.Anti-depressant potential of EAMP was evaluated by forced swimming (FST, tail suspension (TST, and open field tests (OFT. The behavioral findings were further corroborated with estimation of neurotransmitters and their metabolites from mouse brain homogenate. Effect on learning and memory was evaluated by EPM, passive avoidance (PA tests. Further, it was confirmed with assessment of acetylcholinesterase and caspase-3 activity in brain homogenate. Results: EAMP showed significant anti-anxiety activity by increasing the time spent in open arm of EPM, light box of LDB. Social interaction time was increased significantly (p

Mutation of the key residue for extraribosomal function of ribosomal protein S19 cause increased grooming behaviors in mice.

Science.gov (United States)

Chen, Jun; Kaitsuka, Taku; Fujino, Rika; Araki, Kimi; Tomizawa, Kazuhito; Yamamoto, Tetsuro

2016-08-26

Ribosomal protein S19 (RP S19) possesses ribosomal function as RP S19 monomer and extraribosomal function as cross-linked RP S19 oligomers which function as a ligand of the complement 5a (C5a) receptor (CD88). We have generated a Gln137Glu-RP S19 knock-in (KI) mouse, which is shown to possess the weakened extraribosomal function of RP S19. Because whether the extraribosomal function of RP S19 has a role in brain function had been unclear, we performed behavioral analysis on these mice and demonstrated that KI mice displayed an increased grooming behavior during open-field test and elevated plus maze test and an enhanced freezing behavior in contextual fear conditioning test. These results suggest an involvement of RP S19 oligomers in some anxiety-like behavior, especially grooming behavior. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.