Sex-dependent effects of chronic fluoxetine exposure during adolescence on passive avoidance memory, nociception, and prefrontal brain-derived neurotrophic factor mRNA expression

Fluoxetine, a common antidepressant drug, is widely used for mental disorders therapy in adolescents. Previous animal experiments have indicated that exposure to fluoxetine during adolescence leads to persistent behavioral changes and neuroplasticity in the hippocampal formation and cortex which may continue until adulthood. Therefore, in the present experimental study, we examined the effects of chronic fluoxetine exposure (5 mg/kg/day, gavage) throughout adolescence (postnatal day 21-60) on passive avoidance learning and memory, pain sensitivity, and brain-derived neurotrophic factor (BDNF) level in the prefrontal cortex of young adult male and female rats. Passive avoidance learning, memory, and nociception were assessed by the shuttle box and hot plate tests respectively. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was applied to estimate the BDNF mRNA expression. Our data showed that chronic administration of fluoxetine had an increasing effect on passive avoidance memory in female animals. As well as, chronic fluoxetine treatment decreased latency of response to thermal stimulus in male and female rats. The mRNA expression of BDNF in the prefrontal cortex significantly increased in fluoxetine- exposed female rats. In conclusion, chronic fluoxetine treatment has sex-dependent effects on passive avoidance memory and BDNF mRNA expression, but the pain threshold decreases in both sexes. Therefore, passive avoidance memory, pain sensitivity, and the BDNF level are influenced by the manipulation of the serotonergic system.