Sertraline and cocaine-induced locomotion in mice. I: Acute studies

The present study assessed the behavioral and pharmacokinetic interaction between the serotonin uptake blocker sertraline and cocaine in C57BL/6ByJ mice. Pretreatment with sertraline (1-32 mg/kg IP) did not affect the total amount of spontaneous locomotor activity during 50 min following administration of cocaine (15-40 mg/kg IP). At doses of sertraline (16 and 32 mg/kg) much higher than those found to inhibit ex vivo neuronal uptake of serotonin by 50% (1-2 mg/kg), the peak of cocaine-induced locomotor activity was shifted towards a later time. A similar effect was seen after pretreatment with serotonin uptake blockers other than sertraline, and also after desipramine. Sertraline (16 and 32 mg/kg), given 60 min prior to cocaine, did not affect levels of cocaine in brain and plasma, and cocaine administration did not alter the brain level of sertraline. Although female mice were more responsive to cocaine than male mice, they were not different in their response to sertraline.