Companion Animal Research, School of Veterinary Medicine, Azabu University, Sagamihara, Japan.
Psychopharmacology (Berl). 2012 Nov;224(1):201-8. doi: 10.1007/s00213-012-2821-y. Epub 2012 Aug 7.
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.
抗抑郁药物的治疗通常被开处，但即使在动物模型中，关于养育环境和性别对抗抑郁药物反应的差异，也很少有研究发表。
我们使用小鼠模型，研究了养育环境（断奶时间）和性别是否会影响对丙咪嗪治疗的反应的假说。
ICR 小鼠按性别分为四组：早期断奶盐水或丙咪嗪处理组，正常断奶盐水或丙咪嗪处理组。早期断奶在出生后第 14 天进行。所有组均在 6 周龄时开始接受为期 2 周的腹腔内注射药物或载体治疗，并在高架十字迷宫中进行测试，以评估焦虑水平。还通过钙结合蛋白免疫染色检测 calretinin 和 calbindin 来评估海马神经发生，因为它表明神经发生是抗抑郁药行为效应所必需的。
在正常断奶条件下，丙咪嗪治疗降低了雌性而不是雄性的焦虑水平。相比之下，在早期断奶条件下，相同的治疗降低了雄性而不是雌性的焦虑水平。与丙咪嗪治疗对焦虑行为和海马神经发生的反应相关的海马变化见于颗粒细胞外层：在正常断奶条件下，丙咪嗪增加了 calretinin 阳性细胞的数量，但在雄性中而不是在雌性中。然而，在早期断奶条件下，该治疗与雄性相似的变化相关，但与雌性无关。
这些结果表明，养育环境和性别差异与焦虑行为和海马神经发生对丙咪嗪治疗的反应有关。
