Prozac Exposure during Adolescence Enhances Sensitivity to Cocaine in Adulthood

RM 215-218

Diagnosing pediatric populations with major depressive disorder (MDD) was almost unthinkable until several years ago. Children and adolescents who suffer from MDD often develop conduct and anxiety illnesses, and up to 25% develop substance abuse disorders. Consequently, this has resulted in a disproportionate increase in the prevalence of antidepressants prescribed to these populations. In particular, prescription rates of Fluoxetine (FLX), a selective serotonin reuptake inhibitor, are on the rise. Despite the heightened rates of antidepressant use in the population, it is surprising how little is known about the potential long-term consequences resulting from FLX treatment during periods prior to adulthood. To address this issue at the preclinical level, we examined whether FLX (20 mg/kg) exposure during adolescence, or adulthood, results in long-lasting changes in sensitivity to the rewarding effects of cocaine. Specifically, separate groups of adolescent [postnatal day (PD)-35] and adult (PD65) male C57BL/6 mice were exposed to FLX for 15 consecutive days. Three-weeks post antidepressant treatment (PD75 for adolescents and PD105 for adults), mice were assessed on behavioral responsivity to cocaine (0, 2.5, 5, 10, or 20 mg/kg) using the conditional place preference (CPP) paradigm. We found that mice pre-treated with FLX during adolescence (PD35-49), but not adulthood (PD65-79), displayed enhanced preference for environments previously paired with moderately low doses of cocaine ( 5 or 10 mg/kg), when compared to saline pre-tested age-matched controls. Together, our findings indicate that repeated exposure to FLX during the adolescent stage of development increases sensitivity to the rewarding effects of cocaine, later in life.