Altered Sensitivity to the Rewarding Properties of Cocaine in Adult Female c57bl/6 Mice Exposed to Fluoxetine during Adolescence

RM 215

Accumulating preclinical evidence indicates that early-life exposure to psychotropic medications results in long-lasting altered behavioral responses to drugs of abuse – suggesting a risk of enhanced drug liability, later in life. However, to date, these preclinical experimental approaches have been conducted primarily using male subjects. This is surprising given that females, when compared to males, are more likely to be diagnosed with mood-related disorders, and thus be prescribed with psychotropic drugs, such as antidepressants. Therefore, to examine whether long-lasting alterations to the rewarding properties of drugs of abuse are exhibited as a result of juvenile antidepressant exposure, we exposed adolescent female mice to the selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX, Prozac). We selected FLX given that it is the only SSRI approved by the US Food and Drug Administration for the treatment of pediatric depression. Specifically, female C57BL/6 mice were treated with FLX (20 mg/kg) during adolescence (postnatal days [PD] 35-49) and were later assessed in adulthood (PD 70+) on behavioral responsivity to cocaine (0, 2.5, 5, and 7.5 mg/ kg) place conditioning (CPP). Our results show that adult female mice pretreated with FLX during adolescence displayed a decreased preference for environments previously paired with moderately low doses of cocaine, when compared to saline pretreated controls. Collectively, our data suggest that adolescent exposure to the antidepressant FLX causes behavioral adaptations that endure into adulthood, and that are indicative of a decreased sensitivity to the rewarding properties of cocaine.