Effects of sex and rearing environment on imipramine response in mice

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Antidepressant treatments are commonly prescribed, but few studies have been published, even in animal models, on differences in reactivity to antidepressants with respect to rearing environment and sex. Using a mouse model, we investigated the hypothesis that rearing environment (weaning time) and sex could impact responses to imipramine treatment. ICR mice were assigned to four groups for each sex: early weaned saline or imipramine treated, normally weaned saline or imipramine treated. Early weaning was conducted on postnatal day 14. All groups were injected intraperitoneally with drug or vehicle for 2 weeks from the age of 6 weeks and tested in the elevated plus maze to estimate anxiety levels. Hippocampal neurogenesis was also assessed with immunostaining for calretinin and calbindin because it has suggested that neurogenesis is required for the behavioral effects of antidepressants. Imipramine treatment decreased anxiety levels in females, but not in males, in the normal weaning condition. By contrast, the same treatment decreased anxiety levels in males, but not females, in the early weaning condition. Hippocampal changes, which correlated these behavioral responses to imipramine, were seen in the extragranule cell layer: the number of calretinin-positive cells was increased by imipramine in females, but not in males, in the normal weaning condition. In the early weaning condition, however, the treatment was associated with similar changes in males but not in females. The results suggest that rearing environment and sex differences are implicated in responses to imipramine treatment with respect to anxiety behavior and neurogenesis in the hippocampus.