Abstract
Rationale
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.
Objectives
Using a mouse model, we investigated the hypothesis that rearing environment (weaning time) and sex could impact responses to imipramine treatment.
Methods
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.
Results
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.
Conclusions
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.
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Acknowledgments
This work was supported financially by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (#s14760187 and 23248049) and partially supported by a research project grant awarded by the Azabu University.
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Mogi, K., Shimokawa, Y., Nagasawa, M. et al. Effects of sex and rearing environment on imipramine response in mice. Psychopharmacology 224, 201–208 (2012). https://doi.org/10.1007/s00213-012-2821-y
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DOI: https://doi.org/10.1007/s00213-012-2821-y