Fluoxetine treatment reverses the intergenerational impact of maternal separation on fear and anxiety behaviors

- Maternal separation (MS) impaired contextual fear extinction in F1 male generation.
- F2 offspring generated from F1 MS male rats showed low anxiety-like behaviors.
- Fluoxetine treatment in F1 MS males reversed fear extinction impairment.
- Paternal fluoxetine treatment can reverse low anxiety-like behaviors in F2 offspring.

Early life stress increases risks of fear and anxiety related disorders in adulthood, which may be alleviated by fluoxetine treatment. However, the intergenerational impacts of maternal separation (MS) on fear and anxiety behaviors from father to their offspring are little known. And the potential effects of fluoxetine treatment on the intergenerational transmission have not been well tested. Here, we investigated whether fluoxetine can reverse the intergenerational effects of MS on fear and anxiety behaviors. The first generation (F1) male rats were exposed to MS 3 h daily from postnatal day 2-14 and then treated with fluoxetine for four weeks during adulthood before fear conditioning. We found that maternal separation significantly impaired contextual fear extinction in F1 adult male rats but not in their second generation (F2). Although no obvious effects of MS on anxiety were observed in F1 male rats, the F2 offspring displayed a phenotype of low anxiety-like behaviors despite they were reared in normal condition. Fluoxetine treatment in F1 males not only reversed the impairment of fear extinction in F1 males but also the low anxiety-like behaviors in their F2 offspring. These findings highlight the intergenerational impacts of early life stress on fear and anxiety behaviors, and provide a new sight of the intergenerational effect of fluoxetine therapy for early life stress related mental problems.