Sertraline and cocaine-induced locomotion in mice. II. Chronic studies.

The effects of repeated treatment with the serotonin uptake blocker sertraline on cocaine-induced locomotion in female C57BL/6ByJ mice were examined in three paradigms. First, when animals were treated for 2 weeks with a daily injection of 8 mg/kg IP of sertraline (or placebo) and challenged with cocaine (25 mg/kg IP) 1 h after the final sertraline injection, their cocaine-induced locomotion was the same as that of placebo-pretreated controls. Second, animals were treated for 2 weeks with cocaine (25 mg/kg IP once a day) (or saline) and then for 2 weeks with sertraline (8 mg/kg IP once a day) (or placebo). Locomotion induced by cocaine (25 mg/kg IP) administered 1 h after the final sertraline (placebo) injection was higher in cocaine- than saline-pretreated mice (sensitization), but there was no difference between sertraline- and placebo-pretreated animals. Third, daily treatment with sertraline (8 mg/kg IP) did not change the locomotor stimulatory effect of cocaine (25 mg/kg IP) administered after a 3-week continuous infusion of cocaine (22 mg/kg/day SC) by osmotic minipumps or after three, four, or seven injections of cocaine (15 or 25 mg/kg IP). After cocaine administration (25 mg/kg IP), animals pretreated repeatedly with sertraline (8 mg/kg IP once a day for 2 weeks) had the same plasma or brain levels of cocaine as those pretreated with placebo; there was no difference between cocaine- and saline-treated mice in brain levels of sertraline or desmethylsertraline.