Administration of clomipramine to neonatal mice alters stress response behavior and serotonergic gene expressions in adult mice

Early life exposure to antidepressants frequently occurs when pregnant mothers take the medication during late pregnancy. Previous studies in animal models have shown that early exposure to certain antidepressants can alter some behaviors in adulthood. We examined whether the administration of clomipramine, a serotonin reuptake inhibitor, to neonatal mice could result in depression-related behavioral alterations in adult mice. In addition, in an attempt to uncover the mechanism underlying these behavioral changes, we examined the expression of candidate genes in different areas of the brain. Here we show that mice chronically injected with clomipramine specifically during early postnatal development demonstrated depression-like behavior as well as altered stress responses in adulthood. An analysis of the expression of serotonergic genes after exposure to social defeat stress revealed small but significant changes in the expression of 5-HT1A receptor gene (Htr1a) and 5-HTT gene (Slc6a4) in the mice treated with clomipramine compared with the mice injected with saline. We concluded that antidepressant exposure in early days of life could alter stress-related behavior in adulthood and that the behavioral alterations are accompanied by altered serotonergic gene expressions.