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Compulsive behavior in the 5-HT2C receptor knockout mouse.

The efficacy of serotonergic pharmacotherapy indicates that serotonin (5-HT) plays a role in the treatment, if not the etiology, of obsessive-compulsive disorder (OCD). While some clinical evidence implicates 5-HT(2C) receptors in this disorder, a definitive function has yet to be validated. We hypothesized that 5-HT(2C) receptor knockout (KO) mice may display compulsive-like behavior. This paper describes characterization of several distinct, highly organized behaviors in mice lacking functional 5-HT(2C) receptors, which supports a compulsive-like syndrome.Compulsive-like behavior was assessed in male 5-HT(2C) receptor KO and wildtype (WT) mice. Chewing of non-nutritive clay, chewing patterns on plastic-mesh screens, and the frequency of head dipping were measured. 5-HT(2C) receptor KO mice chewed more clay, produced a distinct pattern of "neat" chewing of plastic screens and exhibited reduced habituation of head dipping activity compared to WT mice. We conclude that the 5-HT(2C) receptor null mutant mouse provides a promising model of compulsive behavior and a means to further explore the role of 5-HT in OCD.

Animals↗

Y chromosomal and sex effects on the behavioral stress response in the defensive burying test in wild house mice.

Genetically selected short attack latency (SAL) and long attack latency (LAL) male wild house mice behave differently in the defensive burying test. When challenged, SAL males respond actively with more time spent on defensive burying, whereas LAL males are more passive with more time remaining immobile. The first aim of this study was to find out whether the nonpairing part of the Y chromosome (Y(NPAR)) affects the behavioral stress response in this paradigm. Second, to determine if the differential behavioral profile found in males is also present in females, SAL and LAL females were tested. Third, nonattacking and attacking LAL males were compared. Five behavioral elements were recorded: defensive burying, immobility, rearing, grooming, and exploration. Males were first tested for attack latency. The results show that the Y(NPAR) influences defensive burying. However, the size of this effect is overshadowed by the background of the mice. Furthermore, although females differed from males, they tended to demonstrate the same behavioral profile as males. Nongenetic factors may also play a role, as attacking LAL males showed more defensive burying than nonattacking LAL males.

Aggression↗

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

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.

Animals↗

One-trial tolerance to midazolam is due to enhancement of fear and reduction of anxiolytic-sensitive behaviors in the elevated plus-maze retest in the rat.

The anxiolytic-like effects of benzodiazepines (BZDs) in rats is reduced after a single exposure to the elevated plus-maze test (EPM). Several hypotheses have been formulated but no conclusive explanation exists for this phenomenon called "one-trial tolerance." In this study, we examined this phenomenon further by carrying out an ethopharmacological analysis of the behavior of rats submitted to the EPM in two trials. Rats injected with saline before both trials (control), treated with 1.0 mg/kg of midazolam before both trials (MM), or only before Trial 2 (SM), were exposed to the EPM. The SM group did not differ from the controls in the Trial 1 and Trial 2 conditions. The MM group showed a clear anxioselective profile in Trial 1 and no anxiolytic-like effects in Trial 2. Whereas midazolam injected before the first trial caused no significant change in immobility, there was a pronounced increase in immobility during Trial 2 for all three conditions. These data suggest that the anxiolytic-like action of midazolam in the first trial gives way to the fear-related insensitive behaviors (phobic/avoidance responses) responsible for the one-trial tolerance to BZDs in Trial 2. Furthermore, an additional experiment showed that midazolam does not seem to affect the acquisition of the learned avoidance response since it is present upon retesting even after midazolam administration in Trial 1 (MS group). Rather, the present data suggest an emotional shift from Trial 1 to Trial 2, which leads to change in the responsiveness of the animals to BZDs.

Animals↗

Behavioral effects of acute and chronic imipramine in the elevated T-maze model of anxiety.

The elevated T-maze is an animal model of anxiety, consisting of three elevated arms: one enclosed and two open. Inhibitory avoidance of the open arms-representing learned fear-has been related to generalized anxiety and the unconditioned escape from one of the open arms to panic. In the present study, we investigated the effects of acute and chronic (21 days) administration of imipramine (5, 10, and 15 mg/kg; IP) in male Wistar rats that have been previously exposed for 30 min to one of the open arms of the T-maze, 24 h before the test. The results show that this preexposure shortens the first escape latency, without changing open-arm avoidance. Under these experimental conditions, chronic imipramine exerted anxiolytic-like effects in the two elevated T-maze tasks; impaired the acquisition of inhibitory avoidance and prolonged escape latency from the open arms. Acute imipramine enhanced both avoidance and escape latencies. Both acute and chronic imipramine decreased locomotor activity measured in a square arena. The obtained results are compatible with the view that inhibitory avoidance and one-way escape in the elevated T-maze reflect different types of fear/anxiety, that may be related to generalized anxiety and panic disorder, respectively.

Animals↗

Risk-taking behavior in adolescent mice: psychobiological determinants and early epigenetic influence.

Epidemiological research has emphasized that adolescence is associated with some temperamental and behavioral traits that are typical of this age and that might substantially contribute to both psychological and psychobiological vulnerability. The contribution of the important developmental rearrangements in neurobiological and neuroendocrinological processes has received surprisingly little investigation. The present review summarizes recent work in animal models, indicating that adolescent rodents exhibit marked peculiarities in their spontaneous behavioral repertoire. When compared to adults, adolescents show an unbalanced and 'extremes-oriented' behavior, consisting of an increased novelty seeking, together with decreased novelty-induced stress and anxiety, an increased risk-taking behavior in the plus-maze, as well as elevated levels of impulsivity and restlessness. Age-related discontinuities in the function of monoaminergic systems, which are a main target of abused drugs, can perhaps account for such a profile. In particular, a peculiar function within reward-related dopaminergic brain pathways actually seems to underlie the search for novel and rewarding sensations, as well as changes in the magnitude of psychostimulant effects. The role played by early epigenetic factors in the shaping of novelty-seeking behavior of adolescent and adult rodents are also reviewed. Two examples are considered, namely, subtle variations in the hormonal milieu as a function of intrauterine position and precocious or delayed maturation of nutritional independence as a function of changes in time of weaning. As for spontaneous drug consumption, a prominent vulnerability to the oral intake of nicotine during early adolescence is reported. In conclusion, adolescence in rodents may represent a suitable animal model with enough face- and construct-validity. Actually, this model is able to show behavioral features that resemble those found in human adolescents, including vulnerability to the consumption of psychoactive drugs.

Adolescent↗

Neophobia in spontaneous hypertensive (SHR) and normotensive control (WKY) rats.

Latency of approaching a novel object (white-colored cube) placed in an unfamiliar open field, duration of object exploration, ambulation, rearing, grooming, and defecation were investigated in spontaneous hypertensive rats (SHR), their genetic normotensive controls (WKY), and standard Laboratory rats of Wistar origin (Tif:RAIf). The parameters measured were taken as indices of fear due to novelty (neophobia). Remarkable differences in behavior of all three strains were observed. By comparison to RAIf and WKY rats, SHR showed decreased neophobia as reflected in the significantly shorter latency of approaching the object and enhanced ambulation and rearing activity in the open field. By comparison to RAIf rats SHR also showed reduced grooming and defecation. WKY rats distinguished themselves from both SHR and RAIf by almost total absence of all responses in this test situation. This behavioral suppression was antagonized by 7.5 mg/kg ip of chlordiazepoxide. The results of this study further support the notion that, by comparison to standard laboratory rats, both SHR and WKY rats show possible genetically determined, altered behaviors which are diametrically opposite to each other.

Animals↗

Zinc-induced peripheral anosmia and behavioral responses to novelty in mice: a quantitative-genetic analysis.

Adult male mice were made anosmic by intranasal flushing with a 5% zinc sulfate solution. Twelve behavioral variables were measured in treated as well as saline-irrigated control animals placed in a novel environment. The genetic underpinnings and the genotype-treatment interactions with regard to these behaviors were analyzed in a classical Mendelian cross between the inbred strains C57BL/6 and DBA/2 and in a full 4 X 4 diallel cross, replicated five times, between these strains and strains C3H/St an CPB-K. Based on the hypothesis of an evolutionary history of directional selection for a well-balanced information-processing system, one might expect directional dominance for decrease in exploration after anosmization. Although decreases were found for several behavioral phenotypes, only few and relatively unimportant genotype-treatment interactions were present. This absence of any kind of genetic variation for behavioral change after anosmization points to an extremely strong directional selection which has eliminated all less favorable alleles. The findings support the hypothesis of directional selection for an efficient olfactory information-processing system.

Animals↗