Prozac and puberty: the effects of fluoxetine treatment on neurogenesis in the pubescent hippocampus

Chronic treatment with fluoxetine (Prozac) increases cell proliferation and neurogenesis in the dentate gyrus of the adult male rat (Encinas et al., 2006; Malberg et al., 2000). Therefore neurogenesis was proposed to be a mechanism through which antidepressants alleviate some symptoms of depression (Jacobs et al., 2000; Duman, 2004a; Sapolsky, 2004). Here we tested whether chronic fluoxetine treatment increases cell proliferation and neurogenesis in pubescent and adult female rats. Rats were injected with fluoxetine (5mg/kg) or saline for 14 days. One day later subjects were injected with 5-bromo-2’- deoxyuridine (BrdU; 200mg/ kg), a marker of dividing cells. Rats in experiment 1 were sacrificed 2hrs after BrdU injection to measure cell proliferation. Subjects in experiment 2 were sacrificed at 24 hrs to measure cell proliferation after a full cell cycle. In experiment 3 subjects were sacrificed 28 days after BrdU injection to measure neurogenesis. At all time points fluoxetine increased proliferation and neurogenesis in adult male rats. However, the drug did not alter proliferation or neurogenesis in pubescent males. Proliferation and neurogenesis were elevated during puberty for both sexes, irrespective of treatment. There were no effects of fluoxetine treatment on proliferation or neurogenesis in females at either age, or across the estrous cycle. Immunofluorescent labeling with BrdU and NeuN a marker of mature neurons verified an effect of fluoxetine treatment only in adult male subjects. Double labeling also indicated that cell fate was not altered at any age by treatment. Blood samples were taken to determine whether fluoxetine altered circulating levels of sex and stress hormones 24 hrs or 29 days after treatment. Treatment decreased corticosterone concentrations in pubescent female rats sacrificed at the later time. There were no other hormonal effects of fluoxetine treatment. These data indicate that pubescent rats respond differently to antidepressants than adults. Hormonal changes in the pubescent female seem especially susceptible to the effects of fluoxetine. In addition, fluoxetine may operate differently in adult females than in adult males. Together, these results indicate that antidepressants probably operate via different neuronal mechanisms in adult males than in other age groups or even the other sex.Ph.D.Includes abstractVitaIncludes bibliographical referencesby Georgia E. Hode