Fluoxetine Exposure Results in Decreased Sensitivity to Cocaine and Sucrose Later in Life: A Study in Female C57BL/6 Mice
Preclinical evidence indicates that exposure to psychotropic medications, during early development, results in long-lasting altered responses to stress- and reward-related stimuli. However, these animal studies have been conducted, primarily, using male subjects. This is surprising, given that clinical data suggests that females have a higher likelihood, than their male counterparts, to be diagnosed with mood-related illnesses, and thus, be prescribed with psychotropic medications, mostly antidepressants. Therefore, to examine whether enduring reward-related alterations are exhibited as a result of antidepressant exposure, in female subjects specifically, we exposed C57BL/6 female mice to fluoxetine (FLX; 250 mg/l in their drinking water). Specifically, separate groups of mice were exposed to FLX for 15 consecutive days, either during adolescence (postnatal day [PD] 35-49) or adulthood (PD70-84). Twenty-one days later, the mice were examined on their behavioral reactivity to cocaine (0, 2.5, 5, 7.5 mg/kg) using the condition place preference paradigm, or assessed on the 2-bottle choice sucrose (1%) test. Our results indicate that, regardless of age of antidepressant exposure, female mice pre-exposed to FLX displayed reliable conditioning to the cocaine-paired compartment in a dose-dependent manner. However, when compared to respective age-matched controls, antidepressant pre-exposure decreased the magnitude of conditioning at the 5 and 7.5 mg/kg cocaine doses. Furthermore, FLX pre-exposure reduced sucrose preference, without altering total liquid intake. Collectively, the data suggest that pre-exposure to FLX, during adolescence or adulthood, results in a prolonged decrease in sensitivity to the rewarding properties of both natural and drug rewards, in female C57BL/6 mice.
Flores Ramirez, Francisco Javier, "Fluoxetine Exposure Results in Decreased Sensitivity to Cocaine and Sucrose Later in Life: A Study in Female C57BL/6 Mice" (2018). ETD Collection for University of Texas, El Paso. AAI10814886.