Individual differences in response to psychological stress and chlordiazepoxide in adult mice: Relations with changes in early social milieu

Abstract

Individual differences in the adult behavior of mice have been associated with variations in early social milieu, such as age of weaning and the sex of littermates. To better understand the roles that these two variables play in the organization of a behavioral profile, the long-term effects of their manipulation in CD-1 mice were assessed. On Postnatal Day (PND) 15, mouse litters were split in half. Each half litter contained 4 males or 4 females, or 2 of each sex. At the same time, one half litter was weaned (precocious weaning); the other half was left with the dam (regular weaning). At adulthood (PND 70), the animals were challenged with the benzodiazepine agonist chlordiazepoxide (CDP; at a 0-, 2.5-, or 5.0-mg/kg dose) and assessed in sequential order in an animal model for anxiety (black/white exploration test) and for pain reactivity (hot-plate test, set at 55° ± 1° C) after a 2-min exposure to a threatening stimulus represented by cat urine. Balanced-sex reared males exhibited a shorter latency to leave the white area than did males raised unisexually, being apparently more prompt to react in a novel situation. No such difference appeared in the female group. In the hot-plate test, precocious weaning significantly reduced the latency to lick a forepaw, and prior exposure to cat’s urine induced a clear-cut analgesia. The latter response was dose-dependently reduced by CDP administration in mice raised in a sex-balanced condition only. Baseline activity levels also differed as a consequence of gender and of rearing condition, and were slightly increased by CDP treatment. Overall, these results suggest that subtle variations of social environment early in development can exert long-term effects on both behavioral reactivity to environmental stimuli and on BDZ-induced behavioral changes.