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At least 811 records · Page 45Linked to original sources
PubMed2002

Short-term effects of an environmental enrichment program for adult cynomolgus monkeys.

Behavior patterns (including behavior disorders) of cynomolgus monkeys are established early in life, and exploratory behavior lessens with age. Whether environmental enrichment programs benefit these animals can be questioned, particularly for animals housed short-term. We evaluated the overall effect of our environmental enrichment program in 40 newly arrived male and female adult cynomolgus monkeys to determine whether it impacted animal well-being. Animals allocated into two groups one that received environmental enrichment (the enriched group) and one that did not (the nonenriched, control group) and behaviors were assessed over a 5-week period. We also examined the effect of enrichment on training time for a simple activity (entering a transfer box). Animals that had environmental enrichment made use of additional cage space, toys, and foraging items, but trends in observed in-cage behavior patterns were relatively unchanged throughout the course of the study. After study completion, physical evidence of self-trauma was found in 25% of the nonenriched animals but not in any of those in the enriched group. Enrichment had no notable effect on body weight or training time for a simple activity. Our findings suggest that provision of a comprehensive environmental enrichment program provides a beneficial effect to adult cynomolgus macaques singly housed short-term.

Animal Husbandry↗
PubMed1982

The effect of medial amygdala lesions on instrumental sexual responses in male rats.

In male rats bar press responses reinforced by the contact with estrous females were established during the preoperative training. Bilateral electrolytic lesions of the medial amygdala nuclei caused an impairment of copulatory behavior manifested by the appearance, during male-female contacts, of exploratory behavior or body investigation instead of copulatory behavior. In all subjects such noncopulatory contacts occurred alternately with those when the copulations took place. The latencies of instrumental responses immediately following the contacts during which intromissions took place remained unchanged. It is suggested that the medial amygdala exerts excitatory and regulatory influences on sexual arousal mechanisms in male rats.

Amygdala↗
PubMed2005

Increased measures of anxiety and weight gain in mice lacking the group III metabotropic glutamate receptor mGluR8.

To study the role of the metabotropic glutamate receptor 8 (mGluR8), mice lacking this receptor were generated by homologous recombination. Homozygous mGluR8-deficient mice are about 8% heavier than their wild-type age-matched controls after reaching 4 weeks of age. This weight difference is not caused by an altered food intake and is not exacerbated by feeding the animals a high-fat diet. Moreover, mGluR8-/- mice are mildly insulin resistant, possibly as a result of being overweight. Behavioral testing revealed a reduced locomotor activity of mGluR8-/- mice compared with wild-type mice during the first 3 days in a novel enclosed environment. However after 3 days, the locomotor activities of wild-type and mGluR8-/- mice were similar, suggesting a reduced exploratory behavior of mGluR8-/- mice in a novel enclosed environment. By contrast, there were no genotype differences in locomotor activity in the open field, plus maze, or in total time spent exploring objects during object recognition tests, indicating that there is a dissociation between effects of mGluR8 deficiency in exploratory activity in a novel safe enclosed environment vs. a more anxiogenic novel open environment. The absence of mGluR8 also leads to increased measures of anxiety in the open field and elevated plus maze. Whether the diverse phenotypic differences observed in mGluR8-/- mice result from the misregulation of a unique neural pathway, possibly in the thalamus or hypothalamus, or whether they are the consequence of multiple developmental and functional alterations in synaptic transmission, remains to be determined.

Absorptiometry, Photon↗
PubMed2000

Anxiety-like behavior in rats: a computational model.

This work describes a neural network model of the rat exploratory behavior in the elevated plus-maze, a test used to study anxiety. It involves three parameters: drive to explore; drive to avoid aversive stimuli; and spontaneous locomotor activity. Each network unit corresponds to a specific location in the maze and the connections, only between closest neighbors, represent the possible adjacent places to which a virtual rat can navigate. Competitive learning is used to generate a sequence of network states that correspond to the virtual rat successive locations in the maze. To evaluate the generality of the model it was also tested for two modifications of the elevated plus-maze: one with totally closed arms and the other with totally open arms. The results are compared with data obtained with rats. The simulations are consistent with experimental evidence and may provide an efficient way of describing the anxiety-like rat behavior in the elevated plus-maze. This could be useful for researching the emotional parameters involved in this anxiety animal model.

Animals↗
PubMed1994

Effects of antagonists at the NMDA receptor complex in two models of anxiety.

The effects of an antagonist at the strychnine insensitive glycine site (5,7-dichlorokynurenic acid, i.c.v.), and of noncompetitive (MK-801, i.p.) and competitive (CGP 37849, i.p.; CGP 39551, i.p.; AP-7, i.c.v.) NMDA antagonists were compared with diazepam (i.p.) in two animal models of anxiety (the open field exploratory behavior of non-habituated rats, and the Vogel conflict test). All drugs when applied in appropriate doses increased punished drinking in the Vogel test, without producing any significant changes in free drinking and the stimulus threshold at their lowest anticonflict doses. The effective doses were as follows: diazepam 1.5 and 2.5 mg/kg; MK-801 0.005 and 0.01 mg/kg; CGP 39551 5.0 and 20.0 mg/kg; CGP 37849 1.0 and 2.5 mg/kg; 5,7-dichlorokynurenic acid 5.0 microgram (i.c.v.); AP-7 0.5 microgram (i.c.v.). In the open field diazepam (0.05 mg/kg), MK-801 (0.1 mg/kg), CGP 37849 (0.01, 0.1, 1.0 mg/kg), and AP-7 2.5 micrograms (i.c.v.) significantly increased exploratory activity in the central sectors of the open field (anti-neophobic reaction), without changing motor activity of the rat. MK-801 at the highest tested dose of 0.2 mg/kg significantly stimulated animal locomotor activity. CGP 37849 in the largest dose examined (10 mg/kg) significantly depressed the motor behavior of rats. Overall, it appeared that different NMDA antagonists showed an anxiolytic-like profile, similar to that of the benzodiazepine diazepam. Among different NMDA receptor complex antagonists studied, CGP 37849 was characterized by the largest distinction between the doses showing an anxiolytic-like action in the open field test, and changing rat motor behavior.

2-Amino-5-phosphonovalerate↗
PubMed1995

Peripheral and intracerebroventricular administration of human chorionic gonadotropin alters several hippocampus-associated behaviors in cycling female rats.

Our recent demonstration of receptors for luteinizing hormone (LH)/human chorionic gonadotropin (hCG) in rat brain with the highest density within the hippocampus and dentate gyrus suggests novel functional roles for gonadotropic hormones within the brain. The present study investigated whether 125I-hCG can cross the blood-brain barrier and reach hippocampus and the possible role of hCG in the regulation of several behavioral activities associated with the hippocampal formation in the rat. About 1/100th of peripherally injected 125I-hCG crossed the blood-brain barrier in an intact form and was found in cerebrospinal fluid and in hippocampus. Intraperitoneal (IP) or intracerebroventricular (ICV) injections of highly purified hCG on the morning of proestrus of cycling female rats resulted in changes in several hippocampus-associated behaviors. hCG-treated animals were generally less active and showed less exploratory behavior as compared to saline-injected control animals. There was no difference, however, in latency to enter the open field between hCG-treated and control animals. Taste neophobia was dramatically decreased following IP as well as ICV injection of hCG. No differences were found in the memory component of T-maze performance; however, the hCG-treated rats exhibited decreased stereotypic behavior. In summary, hCG can cross the blood-brain barrier, and peripheral or central administration of hCG affects several hippocampus-associated behaviors suggesting that hippocampal LH/hCG receptors are most likely involved in mediating these effects. Some of the observed behavioral changes have parallels in pregnant women.

Animals↗
PubMed1982

Effects of histamine microinjections into the hippocampus on open-field behavior in rats.

Increasing evidence supports the concept that histamine would subserve neurotransmitter functions in the brain. In hippocampus, some cases of histamine receptors coupled to adenylate cyclase has been described. In our laboratory we were interested in studying the possible physiological role of these histamine receptors and behavior. Unilateral cannulae were stereotaxically implanted in the caudal hippocampus in adult male rats. Forty-eight hours later, after an acute microinjection of histamine (1 microgram), 3-methyl-histamine (1 microgram) or saline (1 microliter), the following behavioral parameters were measured by an observer in an open-field: locomotor, rearing, sniffing, grooming, social sniffing and holding activities. It was observed that histamine inhibited locomotor and rearing activities; whereas, 3-methyl-histamine induced an increase in almost all behaviors. Results support the concept of a probable function of histamine in exploratory behavior in the rat.

Animals↗
PubMed2005

Testosterone's anti-anxiety and analgesic effects may be due in part to actions of its 5alpha-reduced metabolites in the hippocampus.

Although testosterone (T) may have effects to enhance analgesia and reduce anxiety, its effects and mechanisms are not well understood. We hypothesized that if T's anti-anxiety and analgesic effects are due in part to actions of its 5alpha-reduced metabolite (dihydrotestosterone-DHT) and/or its 3alpha-hydroxysteroid dehydrogenase reduced metabolite (3alpha-androstanediol-3alpha-diol), in the hippocampus, then androgen regimens that increase levels of these metabolites in the hippocampus should produce anti-anxiety behavior, and analgesic effects, in gonadectomized (GDX) male rats. In Experiment 1, GDX rats were administered T, DHT, 3alpha-diol (1 mg/kg, SC), or vehicle. In Experiment 2, GDX rats had T, DHT, 3alpha-diol-containing inserts, or empty control inserts applied to the dorsal hippocampus immediately prior to behavioral testing. Androgen-administered rats (SC or intrahippocampal) showed significantly more exploratory behavior in the open field and elevated plus maze, less freezing in response to shock, and longer tailflick and pawlick latencies. These findings suggest that T's anti-anxiety effects may be due in part to actions of its 5alpha-reduced metabolites in the dorsal hippocampus.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1999

Gender impacts behavioral and neurochemical adaptations in ethanol-dependent rats.

Previous investigations have found gender differences in the effects of chronic ethanol exposure on ethanol withdrawal behaviors as well as GABA(A) receptor gene expression. The present investigation extended these studies with additional behavioral and neurochemical measures of ethanol dependence and withdrawal. No significant gender differences in the elevated plus-maze assessment of ethanol withdrawal anxiety behaviors were found. However, the neuroactive steroid, 3alpha,5alpha-THP, increased exploratory behavior in ethanol withdrawn female, but not male, rats. GABA(A) receptor binding assays showed potent competition of [35S]TBPS binding by 3alpha,5alpha-THP. Control females displayed a decreased affinity for 3alpha,5alpha-THP compared to control males, as evidenced by a nearly 30% increase in the IC50 value. There was no significant effect of ethanol withdrawal on 3alpha,5alpha-THP modulation of [35S]TBPS binding. However, gender differences were observed in the effects of chronic ethanol exposure on GABA(A) receptor subunit peptide levels in the hypothalamus. Female rats had a significant increase in peptide levels for the alpha2 and alpha3 but not alpha4 subunit, whereas male rats displayed a significant increase in alpha4 and alpha3 but not alpha2 subunits compared to pair-fed control levels. Chronic ethanol-induced alterations in gene expression in the hypothalamus did not coincide with previous findings in the cerebral cortex. In particular, male rats showed an increase in alpha1 subunit peptide levels in the hypothalamus, whereas significant decreases in this subunit have been observed in the cerebral cortex. Both female and male rats showed significant increases in the alpha3 subunit in the hypothalamus but not the cerebral cortex. Taken together, these studies provide additional support for gender-selective effects of chronic ethanol-elicited adaptations at the molecular level.

Adaptation, Biological↗
PubMed2000

Effects of prenatal AZT+3TC treatment on open field behavior and responsiveness to scopolamine in adult mice.

Treatment of pregnant seropositive women and their neonates with the nucleoside analogs (reverse transcriptase inhibitors) zidovudine (AZT), lamivudine (3TC) and their combination has become a standard of care in industrialized countries to prevent transmission of the HIV-1 virus. Animal studies indicated limited but significant behavioral changes in AZT or 3TC-prenatally exposed offspring, whereas data on the potential neurobehavioral outcomes of AZT+3TC combination are still lacking. The aim of the present study was to assess in mice prenatally exposed to AZT+3TC the functional state of cholinergic muscarinic neuroregulation at adulthood. Pregnant CD-1 mice received per orem twice daily AZT+3TC (160 and 500 mg/kg, respectively) or vehicle solution (NaCl 0.9%) from gestational day (GD) 10 to delivery (GD 19). Locomotor activity, exploratory behavior and responsiveness to the muscarinic cholinergic blocker scopolamine (2 mg/kg) were analyzed at adulthood (PND 70) in offspring of both sexes in an open field test. Results indicated that prenatal AZT+3TC exposure does not influence responsiveness to the muscarinic cholinergic antagonist as measured by analysis of the drug's effects on locomotor and exploratory activity and different behavioral items. However, AZT+3TC-treated mice displayed higher frequency of rearing, and lower frequency and duration of self-grooming behavior, consistent with an effect on dopaminergic neurotransmission. However, this would need confirmatory experiments.

Animals↗
PubMed1990

5HT-2 mediation of acute behavioral effects of hallucinogens in rats.

In rats tested during their first exposure to a Behavioral Pattern Monitor chamber, acute injections of the 5HT-2 agonists mescaline, quipazine, 2,5-dimethoxy-4-iodoamphetamine (DOI), 2,5-dimethoxy-4-methylamphetamine (DOM), or 2,5-dimethoxy-4-ethylamphetamine (DOET) produced an inhibition of locomotor and investigatory behavior during the first 30 min of the test session. This suppression of exploratory behavior was attenuated when rats were familiarized with the testing chamber prior to the administration of DOI. Hence, as previously observed with both LSD and DOM, 5HT-2 agonists appear to potentiate the normal neophobic reaction to a novel environment. The mixed 5HT-1 and 5HT-2 agonist 5-methoxy-N,N-dimethyltryptamine (5MeODMT) also produced a decrease in activity when animals were tested in the novel environment. However, as previously found with 5HT-1A agonists, this effect was unchanged when animals were tested in the familiar environment and may therefore reflect a generalized sedation. The receptor specificity of these differential effects of 5HT-1 and 5HT-2 agonists in this paradigm was tested by assessing the ability of selective 5HT-2 antagonists to block the effects of the agonists. A dose of the 5HT-2 antagonist ketanserin which had no effect by itself significantly reduced the behavioral effects of mescaline, DOM, and quipazine. Similarly, the selective 5HT-2 antagonist ritanserin blocked the effect of quipazine. In contrast, ketanserin had no significant effect on the suppression of activity produced by the 5HT-1A agonist 8-hydroxy-2(di-n-propylamino)tetralin (8OHDPAT).(ABSTRACT TRUNCATED AT 250 WORDS)

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed2000

High social anxiety and low aggression in Fawn-Hooded rats.

The Fawn-Hooded (FH) rat strain, with well-documented changes in their serotonergic and noradrenergic systems, is a putative genetic model for some neuropsychiatric disorders like depression, alcohol abuse, and anxiety. Because social phobia frequently occurs in combination with these disorders and there are no social anxiety-related data in FH rats in the literature, we measured the behavior of FH rats in the social interaction test. In addition, the effects of the anxiogenic Serotonin-2C (5-HT2C) receptor agonist, m-chlorophenylpiperazine (m-CPP), were studied. Male FH, Wistar (W), and Sprague-Dawley (SD) rats were used in two different test conditions of the social interaction test: the high light, unfamiliar arena, associated with high anxiety, and the low light, familiar arena, associated with low anxiety-like behavior. All social behaviors were markedly diminished in FH rats that suggested higher anxiety in these animals. Total social interaction time was reduced by 60-70% in FH rats compared either to W or SD rats under high light, unfamiliar or low light, familiar conditions, respectively. Aggressive behavior was reduced at least by 85% in FH rats. Locomotor activity and exploratory behavior were only minimally, in most comparisons, not significantly affected in FH rats. Total social interaction time, aggression, and locomotor activity were decreased, and self-grooming increased by m-CPP (0.5 mg/kg, ip) in all three strains. m-CPP decreased total social interaction time thus, caused anxiety most efficiently in FH rats (reduced by 69%, 50%, and 55% in FH, W, and SD rats, respectively), but other effects of the drug were similar in the three strains. Our studies provide evidence that the FH rat strain may be a genetic model of social phobia or other anxiety disorders with impaired social behavior.

Aggression↗
PubMed2003

Complexin II is essential for normal neurological function in mice.

Complexins (CPLXs) are modulators of synaptic vesicle release. At 1 year of age, CPLXII knockout (KO) mice appear normal. However, behavioral testing reveals underlying deficits of motor and cognitive function in these mice. We found motor deficits on the rotarod, and learning deficits in the Morris water maze (both acquisition and reversal) and the two-choice swim tank (reversal). The reversal learning deficits are particularly noticeable, being present from the earliest time of testing, when most other behaviors are normal. CPLXII KO mice also fail to develop adult patterns of exploratory behavior in the open field and show deficits in interactive grooming behaviors. The behavioral deficits worsen with age. For example, while rotarod performance is normal until 10 weeks, it is impaired from 24 weeks onwards. Similarly, deficits in spatial learning in the Morris water maze are mild at 8 weeks, but pronounced by 1 year of age. The deficits seen in CPLXII KO mice are not due to physical weakness, since their ability to run, swim and grip is unimpaired. Rather, the mice appear to have deficits of higher function. The deficits seen in CPLXII KO mice are strikingly similar to those seen in the R6/2 model of Huntington's disease (HD) where a progressive depletion of CPLXII is seen. This suggests that depletion of CPLXII contributes to cognitive abnormalities in R6/2 mice. Given that decreased expression of CPLXII is seen in HD and schizophrenic patients, a role for CPLXII depletion should be considered in other diseases where motor, cognitive and psychiatric symptoms co-exist.

Adaptor Proteins, Vesicular Transport↗
PubMed1999

Behavioral profile of quinpirole in agonistic encounters between male mice.

Most neuroleptic drugs that act as dopaminergic D2 receptor antagonists are effective antiaggressive agents. Although the action of D2 antagonists on aggression has been extensively documented, little is known about the influence of D2 agonists. This study was designed to examine the effect of quinpirole (0.2, 0.4 and 0.8 mg/kg i.p.), a potent agonist at D2 receptors,on agonistic behavior elicited by isolation in male mice. Individually housed mice were exposed to anosmic standard opponents 30 min after drug administration and encounters were videotaped and evaluated using an ethologically based analysis. Quinpirole exhibited an ethopharmacological profile characterized by a selective decrease in offensive behaviors (threat and attack) at low doses (0.2 mg/kg) without affecting motility or exploratory behaviors. This action could be related to the activation of presynaptic D2 receptors. In contrast, at higher doses (0.8 mg/kg), this drug produced a behavioral pattern defined by a significant increase in defense/submission and avoidance/fleeing as well as a reduction in digging and social investigation behaviors suggesting that it could also show anxiogenic-like properties.

Aggression↗
PubMed1997

Differential behavioral responses to cocaethylene of Long-Evans and Sprague-Dawley rats: role of serotonin.

Cocaethylene is a neuroactive metabolite derived from the concurrent consumption of cocaine and ethanol. The effects of cocaethylene on locomotor activity, stereotypy, and rearing in Long-Evans and Sprague-Dawley rats were compared. A single cocaine injection (molar equivalent of 60 mumol/kg cocaethylene, intraperitoneal) elicited a robust series of motor output behaviors, including locomotion, stereotypy, and rearing over a 30-minute testing period in Long-Evans rats. In contrast, cocaethylene administration, under comparable testing conditions, produced no significant changes in locomotor and investigatory behaviors. Because cocaethylene has relatively little impact on serotonin (5-HT) reuptake as opposed to reuptake of dopamine, we pretreated Long-Evans rats with fluoxetine (10 mg/kg; i.p.), a selective 5-HT reuptake inhibitor. Fluoxetine profoundly augmented cocaethylene-stimulated behaviors in this rat phenotype. To examine whether other rat strains exhibit a similar response to cocaethylene, Sprague-Dawley rats were injected (i.p.) with cocaethylene and their behavior patterns monitored over a 30-minute testing period. Cocaethylene produced marked locomotor and exploratory behaviors in this strain, suggesting therefore that Long-Evans and Sprague-Dawley rat differ in their response to cocaethylene. To relate these behavioral differences to possible structural differences in the neuronal density of dopaminergic or serotonergic neurons, Long-Evans and Sprague-Dawley brains were evaluated for tyrosine hydroxylase and 5-HT immunocytochemistry. No gross morphological differences in neuronal architecture or density were found in the ventral tegmental area or dorsal raphe nucleus of the two rat phenotypes. These results indicate that two commonly used rat strains show a differential response to cocaethylene and the neurochemical basis for this behavioral difference may be related to synaptic 5-HT bioavailability.

Animals↗
PubMed2004

Accelerated extinction of conditioned taste aversion in P301L tau transgenic mice.

Neurofibrillary tangles, insoluble protein deposits composed of filamentous tau aggregates, are neuropathological hallmarks of Alzheimer's disease and familial frontotemporal dementia (FTDP-17). Transgenic mice expressing the FTDP-17 mutation P301L of tau recapitulate key features of the human pathology, that is, tau proteins aggregate and neurofibrillary tangles begin to appear in the amygdala at 6 months of age. To detect early signs of tau aggregate-associated changes, we investigated behavioral alterations and cognitive deficits in such mice using an amygdala-specific test battery for anxiety-related and cognitive behavior. P301L mice had anxiety levels not different from wild-types, but their exploratory behavior was significantly increased. Acquisition of a fear response to tone and context as well as taste aversion was comparable to wild-types. However, extinction of a conditioned taste aversion was significantly accelerated. We conclude that already aggregation of tau proteins not yet accompanied by massive formation of neurofibrillary tangles causes selective behavioral deficits.

Animals↗
PubMed1991

Effects of neonatal administration of vasopressin on cardiac and behavioral responses to emotional stress in adult male rats.

Arginine-8-vasopressin (AVP) was administered subcutaneously on postnatal days 3-7 in a high (10 micrograms/100 g b.wt.) or a low dose (1 microgram/100 g b.wt.) to male Wistar rats. Control pups were untreated or saline injected. Behavioral observations in a complex maze after maturation indicated that neonatal administration of AVP increases exploratory behavior in this novel environment in a dose-dependent way. Cardiac monitoring during the conditioned emotional stress of fear of inescapable electric footshock showed that only the high dose of AVP attenuates the bradycardiac stress response. The analysis of cardiac responses also suggested an adult hyposensitivity to AVP in rats treated neonatally with AVP. In addition, the low dose of neonatal AVP was impairing the retention of a passive avoidance behavior. The data indicate that the neonatal administration of AVP exerts long-term effects upon the behavioral adaptation to novelty and memory processes related to emotional stress. That neonatal AVP is less effective in influencing adult vagally mediated cardiac stress responses suggests differences in the developmental sensitivity ("critical periods") of the central vasopressinergic systems involved in the regulation of behavior and autonomic functioning.

Animals↗