Prozac during puberty: distinctive effects on neurogenesis as a function of age and sex

Neurogenesis is a possible substrate through which antidepressants alleviate symptoms of depression. In adult male rodents and primates, chronic treatment with fluoxetine increases neurogenesis in the hippocampal formation. Little is known about the effects of the antidepressant on neurogenesis during puberty or in female animals at any age. Therefore we examined the effects of chronic fluoxetine treatment on cell proliferation and survival in male and female rats during puberty and adulthood. Adult and peri-pubescent male and female rats were treated chronically with fluoxetine (Prozac, 5 mg/kg) or saline. Subsequently rats received a single injection of 5-bromo-2'-deoxyuridine (BrdU; 200 mg/kg) to label DNA synthesis. Rats were sacrificed 2 h, 24 h, or 28 days after BrdU injection to examine cell proliferation, survival and cell fate. Fluoxetine increased cell proliferation in adult male rats but not in peri-pubescent males or female rats of any age or stage of the estrous cycle. Treatment did not alter the number of surviving cells in the male hippocampus but decreased survival in the female hippocampus. Thus, fluoxetine has distinctive effects on neurogenesis as a function of age and sex. Circulating levels of the stress hormone corticosterone were also examined. Treatment of female rats with fluoxetine during puberty decreased circulating levels of corticosterone in adults, even in the absence of the drug suggesting disruption of maturation of the hypothalamic-pituitary-adrenal axis.