Effects of adolescent administration of fluoxetine on novel object recognition memory, anxiety-like behaviors, and hippocampal brain-derived neurotrophic factor level.

AIMS: Fluoxetine (FLX) is a common selective serotonin reuptake inhibitor, which is used in adolescents with psychiatric disorders. Controversial results have been obtained in different studies about the effects of FLX on cognitive functions. The present study was designed to examine the effects of chronic FLX exposure during adolescence on cognitive function, anxiety-like behaviors, and hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression among adult male and female rats. MAIN METHODS: The sex-dependent effects of FLX chronic administration during adolescence (5 mg/kg/day, gavage) on short-term novel object recognition memory (NORM), anxiety-like behaviors, and BDNF mRNA expression in the hippocampus were examined. NORM and anxiety-like behaviors were assessed by novel object recognition, open field, and elevated plus-maze (EPM) tests, respectively. The expression of BDNF mRNA was also evaluated by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). KEY FINDINGS: The present findings revealed the dysfunction of short-term NORM among the adolescent male and female rats exposed to FLX, while the mRNA expression of BDNF was significantly higher among the males. Moreover, adolescent FLX administration had different effects on the anxiety-like behaviors of the male and female rats. Adolescent FLX treatment also decreased the body weight of the male animals. SIGNIFICANCE: In conclusion, adolescent FLX treatment impairs cognitive functions in both sexes and increases BDNF mRNA expression in the hippocampus of the male animals. FLX administration during adolescence has sex-dependent effects on anxiety-like behaviors. These findings indicate that the impairment of cognitive functions can occur following the adolescent manipulation of the serotonergic system. Therefore, the side effects of chronic FLX administration during adolescence should be more considered.

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.