Effects of postnatal exposure to fluoxetine: behavioral and neurogenesis in juvenile and adult mice.

Perinatal exposure to antidepressants may have long term consequences in affective behaviors during childhood. These impairments have been also well characterized in adult mice after postnatal exposition to selective serotonin reuptake inhibitor (SSRI) antidepressants. Nevertheless, the impact of this kind of exposition on memory tasks as well as on the process of adult neurogenesis has been less explored so far. We orally treated C57BL/6 male and female mice from Postnatal day 2 (P2) to P14 with the SSRI fluoxetine (10 mg/kg) or vehicle. Proliferation and survival of hippocampal newborn neurons was analyzed in P90 mice by means of Ki67 and BrdU labeling, respectively. In addition, 3-weeks-old and 3-month-old mice treated with SSRI were assayed in the memory object recognition test and performed significantly worse than control animals. Similarly, in the object pattern separation test, fluoxetine-treated adult mice were less able to pattern separate, an ability linked to the role of immature neurons. Anxiety-like behaviors were evaluated by novelty suppressed feeding test and elevated plus maze, and were more pronounced in antidepressant-treated animals. Furthermore, weight gain was measured with marked reductions in treated mice at juvenile and adult age. All in all, our results show that early exposition to SSRI antidepressants in mice affects the development of newborn neurons in the hippocampus with lasting consequences on memory abilities and anxious behaviors.