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PubMedDate not supplied

Open field behavior of rats reared in different social conditions: the effects of stress and imipramine.

Behavioral changes in rats divided on the weaning day into two groups (crowded and isolated) were studied in the computerized open field. At the end of the experiment the effects of an acute stress (1 h long immobilization) on open field behavior, body weight and body temperature, were examined. In a separate experiment both groups of rats were chronically pretreated with tricyclic antidepressant imipramine (5.0 mg/kg, po), and subsequently exposed to the same stress procedure. Social deprivation significantly enhanced spontaneous locomotion and exploratory activity. Restraint stress significantly decreased exploration, body weight and temperature, in the isolated animals only. Chronic pretreatment of rats with imipramine significantly attenuated the effect of stress on motor and exploratory behavior, as well as stress-induced changes in body weight and temperature, in the group of isolated animals. The present data indicate sensitization to stress of behavioral and vegetative processes in socially deprived animals. The relationship between rearing conditions and behavioral and vegetative reactivity to the environmental challenges is confirmed.

Acute Disease↗

PubMed1991

NTP technical report on the toxicity studies of of n-Hexane in B6C3F1 Mice (Inhalation Studies) (CAS No. 110-54-3).

Thirteen-week inhalation toxicity studies of n-hexane were conducted with B6C3F1 mice of each sex exposed to 0, 500, 1,000, 4,000, or 10,000 ppm, 6 hours per day, 5 days per week or to 1,000 ppm, 22 hours per day (referred to as 1,000c), 5 days per week. All mice lived to the end of the studies. The final mean body weights of mice exposed to 1,000c ppm or 10,000 ppm were 10% or 17% lower than that of the controls for males and 0% or 6% lower for females. Hematologic analyses were performed on whole blood samples collected at the end of the 13-week exposure. Segmented neutrophils were significantly increased in male mice exposed to 10,000 ppm. A battery of behavioral measurements was conducted on mice, and the only parameter affected was locomotor activity, which was decreased in female mice at 1,000c ppm and 10,000 ppm. The test battery performed included forelimb and hind limb grip strength, motor activity and exploratory behavior, acoustic startle response, foot splay, and analgesia response. Compound-related lesions of the nasal turbinates were seen in all groups of exposed mice except males exposed to 500 or 4,000 ppm. At the 10,000-ppm concentration, nasal lesions included inflammatory, erosive, and regenerative lesions of the olfactory and respiratory epithelium; luminal exudation and metaplastic lesions of the olfactory epithelium; and fibrosis of the submucosa. Lymphoid hyperplasia of the mandibular lymph nodes and neutrophilic hyperplasia of the bone marrow were also seen. At lower concentrations, lesions were not present in all mice and were limited to minimal regeneration or metaplasia of the olfactory epithelium. A few paranodal swellings in the teased fibers of the tibial nerve were observed in 3/4 males and 3/4 females exposed to 10,000 ppm, 3/4 males and 3/4 females exposed to 1,000c ppm, and 0/4 male and 0/4 female controls; the severity of the lesions was minimal. Neither segmental demyelination nor distal axonal degeneration was seen. Exposure of mice to n-hexane at concentrations up to 10,000 ppm resulted in only minimal toxicity. Paranodal swellings seen in nerves at 1,000c ppm and at 10,000 ppm were considered to be minimal nerve damage that would not result in paralysis. Exposure- related lesions of the nasal cavity occurred after n-hexane exposure, but minimal or no effects were seen at 1,000 ppm or below. Synonyms: Hexyl hydride. (NOTE: These studies were supported in part by funds from the Comprehensive Environmental Response, Compensation, and Liability Act trust fund (Superfund) by an interagency agreement with the Agency for Toxic Substances and Disease Registry, U.S. Public Health Service.)

Journal Article↗

PubMed1982

Histamine-induced arousal in the conscious and pentobarbital-pretreated rat.

Histamine has been shown to possess many neurotransmitter-like properties, and a variety of studies indicate that central histamine may function in modulating behavioral arousal. To examine this possibility further, histamine was administered into the lateral cerebral ventricles of the conscious and pentobarbital-anesthetized rat. In the conscious animal, histamine induced a significant increase in spontaneous motor activity which consisted of increased grooming and exploratory behaviors (sniffing, rearing and locomotion) as compared to saline-treated controls. In the pentobarbital-pretreated rat, histamine caused a dose-related decrease in narcosis duration and hypothermia without altering the disposition of pentobarbital in brain or plasma. Administration of compounds structurally related to histamine did not alter spontaneous activity or shorten narcosis duration. While pretreatment with the H2-histamine antagonist, cimetidine, was no effective, H1-histamine antagonists were found to abolish histamine-induced arousal. Administration of haloperidol in doses that significantly attenuated increased spontaneous motor activity by amphetamine did not alter histamine-induced hyperactivity. Likewise, atropine did not significantly alter histamine-induced arousal. These data support the hypothesis that histamine may function in modulating behavioral arousal.

Animals↗

PubMed1995

Behavioural consequences of maternal exposure to natural cannabinoids in rats.

Cannabis sativa preparations (hashish, marijuana) are the most widely used illicit drugs during pregnancy in Western countries. The possible long-term consequences for the child of in utero exposure to cannabis derivatives are still poorly understood. Animal models of perinatal cannabinoid exposure provide a useful tool for examining the developmental effects of cannabinoids. Behavioral consequences of maternal exposure to either cannabis preparations or to its main psychoactive component, delta 9-tetrahydrocannabinol (THC) in rat models are reviewed in this paper. Maternal exposure to cannabinoids resulted in alteration in the pattern of ontogeny of spontaneous locomotor and exploratory behavior in the offspring. Adult animals exposed during gestational and lactational periods exhibited persistent alterations in the behavioral response to novelty, social interactions, sexual orientation and sexual behavior. They also showed a lack of habituation and reactivity to different illumination conditions. Adult offspring of both sexes also displayed a characteristic increase in spontaneous and water-induced grooming behavior. Some of the effects were dependent on the sex of the animals being studied, and the dose of cannabinoid administered to the mother during gestational and lactational periods. Maternal exposure to low doses of THC sensitized the adult offspring of both sexes to the reinforcing effects of morphine, as measured in a conditioned place preference paradigm. The existence of sexual dimorphisms on the developmental effects of cannabinoids, the role of sex steroids, glucocorticoids, and pituitary hormones, the possible participation of cortical projecting monoaminergic systems, and the mediation of the recently described cannabinoid receptors are also analyzed. The information obtained in animal studies is compared to the few data available on the long-term behavioral and cognitive effects on in utero exposure to cannabis in humans.

Abnormalities, Drug-Induced↗

PubMed2005

Enhanced learning of normal adult rodents by repeated oral administration of soybean transphosphatidylated phosphatidylserine.

Soybean lecithin transphosphatidylated phosphatidylserine (SB-tPS) is already known to improve the learning ability of aged or drug-induced amnesic rodents. In this study, its effect on normal adult rodents was evaluated using several learning tasks. Firstly, three behavioral tests (open-field, Y-maze, and active avoidance test) were consecutively carried out after the daily oral administration of SB-tPS (50 mg/kg per day, for 34 days). Repeated oral administration of SB-tPS did not affect either exploratory behavior in the open-field test or spontaneous alternation behavior in the Y-maze test, while mice pretreated with SB-tPS showed significant enhancement of conditioned avoidance response. Secondly, the brightness discrimination test was used to evaluate the effect of SB-tPS on learning ability. The daily oral administration of SB-tPS (50 mg/kg per day, for 27 days) to normal rats significantly increased the correct response ratio in the brightness discrimination test. Finally, to elucidate the necessity of SB-tPS pretreatment, another active avoidance test was carried out, and no enhancement of conditioned avoidance response was observed in non-pretreated mice. These results suggest that repeated administration of SB-tPS could enhance the learning ability of normal adult rodents as those of aged ones.

Acetylcholine↗

PubMed2002

Influence of forced swimming-induced stress on the anxiolytic-like effect of 5HT(1A) agents in mice.

RATIONALE: Stress has been related to both anxiety and mood disorders. Forced swimming (FS) is a type of stress that is able to modify the activity of serotonin (5-HT) and GABA in the central nervous system. 5-HT(1A) compounds have been shown to be anxiolytic in a variety of behavioral models and in clinical studies. OBJECTIVE: The main purpose of the present study was to analyze the effect of FS on the anxiolytic-like actions of three 5-HT(1A) compounds. METHODS: Stressed (ST) and unstressed (UST) mice were evaluated in the exploratory behavior test (EBT) or burying behavior test (BBT). In addition, the action of increasing doses of the 5-HT(1A) compounds buspirone, 8-OH-DPAT and indorenate in ST and UST mice was analyzed using the EBT. A spontaneous ambulatory behavior test was carried out immediately after the anxiety tests. RESULTS: One session of FS induced anxiolytic-like behavior in mice tested in both the EBT and the BBT. This effect of FS was blocked by a previous administration of either picrotoxin or WAY 100635. The 5-HT(1A) compounds produced a clear anxiolytic-like effect in UST animals. By contrast, with low doses of either 8-OH-DPAT (0.01 mg/kg), buspirone (0.03 mg/kg) or indorenate (0.3, 0.6 mg/kg) ST mice showed a decrease in the anti-anxiety-like effect observed after FS. No change in ambulation that could mask the results of the anxiety test was registered. CONCLUSIONS: The present data provide evidence that FS induces changes in the effect of 5-HT(1A) agents. The participation of the 5-HT and/or GABA systems in these stress-induced effects is discussed.

5-Methoxytryptamine↗

PubMed1991

A scaling approach to find order parameters quantifying the effects of dopaminergic agents on unconditioned motor activity in rats.

1. Three experiments were conducted in the Behavioral Pattern Monitor (BPM) to assess the effects of the D1 agonist SKF-38393, the D2 agonist quinpirole, and the interaction of the D2 antagonists haloperidol with amphetamine or cocaine on the amount, the structure, and the unpredictability of micro-events of rat exploratory behavior. 2. SKF-38393 (0.3, 1.0, 3.0, and 10.0 mg/kg) did not change the amount of motor behavior indicated by the temporal scaling exponent alpha, a descriptor of the local degree of acting, during a 60 min exposure in the BPM. However, SKF-38393 (3.0, and 10.0 mg/kg) significantly increased the spatial scaling exponent d, indicating an increased component of local circumscribed movements. 3. Quinpirole (0.03, 0.1, 0.3, and 1.0 mg/kg) produced a biphasic dose response with respect to the amount of motor behavior. Low doses (0.03, 0.1) significantly decreased the local degree of acting, whereas alpha returned to control group levels for higher doses (0.3, 1.0 mg/kg). The change in activity was accompanied by a significant increase of local movements, i.e. d was increased for the lower doses. 4. Haloperidol (15.0 micrograms/kg) reduced a slightly increased d measure for amphetamine (1.0 mg/kg) treated animals and increased a significantly reduced d for cocaine (20.0 mg/kg) treated animals, without affecting the increases of motor activity induced by both treatments. 5. It is concluded that the structure of motor activity provides an important measure of unconditioned motor behavior, which can be affected independently of the typically measured amount of motor activity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2003

Dietary fatty acids alter blood pressure, behavior and brain membrane composition of hypertensive rats.

The beneficial effect of dietary n-3 polyunsaturated fatty acids (PUFAs) on developing hypertension has been repeatedly demonstrated. However, related changes in brain membrane composition and its cognitive correlates have remained unclear. Our study aimed at a comprehensive analysis of behavior and cerebral fatty acid concentration in hypertension after long-term PUFA-rich dietary treatment. Hypertensive and normotensive rats were provided a placebo, or one of two PUFA-enriched diets with a reduced (n-6)/(n-3) ratio for 75 weeks. Exploratory behavior and spatial learning capacity were tested. Systolic blood pressure (BP) was repeatedly measured. Finally, brain fatty acid composition was analyzed by gas chromatography. Hypertensive rats exhibited more active exploration but impaired spatial learning compared to normotensives. Both diets reduced BP, increased PUFA and monounsaturated fatty acid (MUFA) concentration, and reduced saturated fatty acid content in brain. The level of cerebral PUFAs and MUFAs was lower in hypertensive than in normotensive rats. Furthermore, BP positively, while spatial learning negatively correlated with cerebral (n-6)/(n-3) PUFA ratio. We concluded that regular n-3 PUFA consumption could prevent the development of hypertension, but reached only a very delicate improvement in spatial learning. Furthermore, we consider a potential role of metabolically generated MUFAs in the beneficial effects of PUFA supplementation.

Animals↗

PubMed1978

Somatic, behavioral, and reproductive disturbances in mice following neonatal administration of sodium L-aspartate.

Sodium L-aspartate (ASP) was administered to neonatal mice according to an increasing dose schedule from Days 2--11 after birth. Adult ASP-treated animals showed large increases in body weight over controls along with stunted body length. The ASP group also showed decreases in locomotor and exploratory behavior. Reproductive dysfunction occurred in both female and male ASP-treated animals. Among treated animals, females had fewer pregnancies and smaller litters while males showed reduced fertility. Evidence of multiple endocrine dysfunction in ASP-treated animals was reflected by decreased pituitary, thyroid, ovaries and tested weights, along with delayed onset of puberty in females. These results demonstrate that sodium L-aspartate produces a syndrome similar to that seen following the administration of monosodium L-glutamate.

Animals↗

PubMed1998

Targeting disruption of histamine H1 receptors in mice: behavioral and neurochemical characterization.

With gene targeting, one can practically knock out a gene in vivo and create a mutant organism that completely lacks the gene product. The mutant mice lacking histamine H1 receptors was generated by the method of gene targeting. In brains of homozygous mutant mice, no specific binding of [3H]pyrilamine was seen. The mutant mice showed impaired locomotor activity and exploratory behavior in an open field and activity wheel. Behaviors of the mutant mice were examined with several other tasks such as passive avoidance test, resident-intruder aggression test and formalin test to clarify the role for the H1 receptors in behaviors. Behavioral changes observed in the mutant mice are almost compatible with those obtained by the classical pharmacological tools. In correlation to the behavioral changes in the mutant mice, 5-hydroxytryptamine release was significantly increased in the brains of mutant mice.

Animals↗

PubMed2003

Conflict as a determinant of rat behavior in three types of elevated plus-maze.

Three groups of rats were tested in different types of elevated plus-mazes, a normal one (two closed and two open arms), a totally closed one (four closed arms) and a totally open (four open arms). Closed arms were surrounded by 40-cm high wooden walls and open arms were surrounded by 0.5-cm high transparent Plexiglas ledges. As expected, in the closed maze rats explored equally all the arms, both in terms of time and frequency of entries, as well as in exploration of the extremities. Rats in the totally open maze also presented a similar pattern of exploration, that is, no significant differences were found between the results obtained with the closed and the open mazes in terms of central and extremities exploration. It is suggested that the typical behavior of rats in the conventional elevated plus-maze is caused by the contrasting characteristics of open and closed arms rather than by the physical aversive characteristics of the open arms per se. Results also confirm a prediction made by a computer model simulating rat exploratory behavior in virtual mazes, normal, totally open and totally closed.

Journal Article↗

PubMed2005

Imprinted Nesp55 influences behavioral reactivity to novel environments.

Genomic imprinting results in parent-of-origin-dependent monoallelic expression of selected genes. Although their importance in development and physiology is recognized, few imprinted genes have been investigated for their effects on brain function. Gnas is a complex imprinted locus whose gene products are involved in early postnatal adaptations and neuroendocrine functions. Gnas encodes the stimulatory G-protein subunit Gsalpha and two other imprinted protein-coding transcripts. Of these, the Nesp transcript, expressed exclusively from the maternal allele, codes for neuroendocrine secretory protein 55 (Nesp55), a chromogranin-like polypeptide associated with the constitutive secretory pathway but with an unknown function. Nesp is expressed in restricted brain nuclei, suggesting an involvement in specific behaviors. We have generated a knockout of Nesp55 in mice. Nesp55-deficient mice develop normally, excluding a role of this protein in the severe postnatal effects associated with imprinting of the Gnas cluster. Behavioral analysis of adult Nesp55 mutants revealed, in three separate tasks, abnormal reactivity to novel environments independent of general locomotor activity and anxiety. This phenotype may be related to prominent Nesp55 expression in the noradrenergic locus coeruleus. These results indicate a role of maternally expressed Nesp55 in controlling exploratory behavior and are the first demonstration that imprinted genes affect such a fundamental behavior.

Adaptation, Psychological↗

PubMed1999

Selection, evolution of behavior and animal models in behavioral neuroscience.

We investigated whether genetic differences in various forms of intraspecific aggression and anxiety in four different genetic lines of mice (i.e. wild, outbred Swiss-CD1, inbred DBA/2 and inbred C57/BL6N) may reflect modifications in behavioral strategy. Experiments 1 and 2 used ethologically based paradigms to analyze aggressive and anxiety responses both in social (i.e. aggression) and non-social (i.e. novel environment exploration) contexts. In Experiment 3, an anxiolytic drug (chlordiazepoxide (CDP)) was used to examine possible differences in proximal mechanisms underlying anxiety-related behaviors. The data show that intrasexual aggression, infanticide and maternal aggressions are related and covarying. Genetic lines with the highest levels of intermale attack (i.e. Wild and Swiss-CD1) also have highest levels of infanticide, interfemale attack and maternal aggression but, interestingly, the lowest levels of anxiety. In fact, exploratory behavior is lower and risk assessment behavior markedly higher in DBA/2 and C57/BL6N mice (i.e. the less aggressive strains) compared to Swiss and Wild genetic lines. Although reproductive status influences anxiety levels in female mice, our findings show that (contrary to previous studies) lactating mice are more anxious than virgin females in terms of risk assessment activities. These data demonstrate the importance of studying behavior in a more ecologically-relevant context which emphasizes the function of behavior in a specific situation. Moreover, differential strain sensitivity to the behavioral effects of CDP suggests that genetic lines of mice may differ in the underlying mechanisms mediating behavior. It is therefore possible that artificial selection of different genotypes has resulted in differences in proximate mechanisms modulating the levels of aggression and anxiety, thereby leading to modification of social behavior. Overall, the results presented here suggest that subtle genetic alterations in specific underlying neural mechanisms are likely to cause profound effects on behavioral responses and their adaptive significance. Implications for behavioral neuroscience research that seeks to understand both the proximal and ultimate mechanisms of behavior are discussed.

Animals↗

PubMed2002

Misguided axonal projections, neural cell adhesion molecule 180 mRNA upregulation, and altered behavior in mice deficient for the close homolog of L1.

Cell recognition molecules are involved in nervous system development and participate in synaptic plasticity in the adult brain. The close homolog of L1 (CHL1), a recently identified member of the L1 family of cell adhesion molecules, is expressed by neurons and glia in the central nervous system and by Schwann cells in the peripheral nervous system in a pattern overlapping, but distinct from, the other members of the L1 family. In humans, CHL1 (also referred to as CALL) is a candidate gene for 3p- syndrome-associated mental impairment. In the present study, we generated and analyzed CHL1-deficient mice. At the morphological level, these mice showed alterations of hippocampal mossy fiber organization and of olfactory axon projections. Expression of the mRNA of the synapse-specific neural cell adhesion molecule 180 isoform was upregulated in adult CHL1-deficient mice, but the mRNA levels of several other recognition molecules were not changed. The behavior of CHL1-deficient mice in the open field, the elevated plus maze, and the Morris water maze indicated that the mutant animals reacted differently to their environment. Our data show that the permanent absence of CHL1 results in misguided axonal projections and aberrant axonal connectivity and alters the exploratory behavior in novel environments, suggesting deficits in information processing in CHL1-deficient mice.

Animals↗

PubMed1991

Pyrethroid insecticides and pregnancy: effect on physical and behavioral development of rats.

We investigated the prenatal effects of cyhalothrin exposure on the physical and behavioral development of infant and adult rats. Female rats were treated by dermal exposure with a 0.018% cyhalothrin aqueous solution (1 ml/d) or the cyhalothrin vehicle during their entire pregnancy. The pesticide delayed development of fur, the ear and eye openings and descent of the testes in the offspring. The exploratory behavior of the rats prenatally exposed to cyhalothrin decreased. No differences were observed between control and experimental animals in inhibitory avoidance tasks at 90 d of age in open field activity. Alterations in physical parameters and possible effects of the pesticide on epidermal growth factor and hormonal levels were considered. Since no overt of signs of maternal or neonatal toxicity were observed, the decrease in adult motivational behavior was attributed to a specific effect of the pesticide administered during the prenatal period. We concluded that prenatal cyhalothrin exposure induced subtle and persistent changes in the physical development and behavior of rats.

Animals↗

PubMed2005

Spatial navigation and causal analysis in a brain-based device modeling cortical-hippocampal interactions.

We describe Darwin X, a physical device that interacts with a real environment, whose behavior is guided by a simulated nervous system incorporating aspects of the detailed anatomy and physiology of the hippocampus and its surrounding regions. This brain-based device integrates cues from its environment and solves a spatial memory task. The responses of simulated neuronal units in the hippocampal areas during its exploratory behavior are comparable to place cells in the rodent hippocampus and emerged by associating sensory cues during exploration. To identify different functional hippocampal pathways and their influence on behavior, we employed a time series analysis that distinguishes causal interactions within and between simulated hippocampal and neocortical regions while the device is engaged in a spatial memory task. Our analysis identified different functional pathways within the neural simulation and prompts novel predictions about the influence of the perforant path, the trisynaptic loop and hippocampal-cortical interactions on place cell activity and behavior during navigation. Moreover, this causal time series analysis may be useful in analyzing networks in general.

Animals↗

PubMed1999

Effects of chronic nicotine administration on locomotion depend on rat sex and housing condition.

Nicotine's behavioral actions in the human smoker by self-report depend, in part, on the individual's gender and environment. The purpose of the present experiment was to determine whether effects of nicotine on unconditioned behaviors of rats also depend on sex and environmental conditions. Long-Evans rats (96 males and 96 females) living in individual or grouped housing were administered saline or 12 mg/kg/day nicotine via osmotic minipump for 14 days. Horizontal activity (a measure of overall activity and arousal), vertical activity (a measure of exploratory behavior), and center time (a possible index of anxiety) were measured on Day 10 of drug administration and on Day 2 of nicotine cessation. Group housing decreased horizontal and vertical activity and center time, with effects occurring sooner in females. Nicotine's effects depended on housing and sex. For males, nicotine altered indices of arousal and exploration, increasing these variables for group-housed males but decreasing them for individually housed males. For females, nicotine altered possible indices of anxiety, reducing anxiety for group-housed females. In cessation, housing effects continued in females and appeared more robustly in males. Results indicate that nicotine's chronic effects depend on subjects' sex and living environment.

Animals↗

PubMed2003

The effects of Coenzyme Q10 on locomotor and behavioral activity in young and aged C57BL/6 mice.

To explore the possibility that Coenzyme Q10 (CoQ10) supplementation stabilizes psychomotor behavioral function in the aging organism, the behavioral effects of CoQ10 were evaluated in young adult male C57BL/6 mice (3 months of age) and aged C57BL/6 mice (24 months of age). Mice treated with CoQ10 exhibited significantly greater locomotor activity as reflected by an increase in square crosses than non-drug controls. The administration of CoQ10 increased all aspects of exploratory behavior in the open field. The effect was uniform across all mice and did not interact with age. Younger animals and aged animals treated with CoQ10 may adapt rapidly to novel areas, or they are less fearful of exploration. The behavioral activation observed in CoQ10 treated mice may be the result of increased locomotor activity, psychomotor stimulation, or decreased anxiety.

Aging↗