BUSPIRONE ENHANCES DULOXETINE-INDUCED AND FLUOXETINE-INDUCED INCREASES IN DIALYSATE LEVELS OF DOPAMINE AND NORADRENALINE, BUT NOT SEROTONIN, IN THE FRONTAL-CORTEX OF FREELY MOVING RATS

A serotonin (5-HT)(1A) receptor partial agonist, buspirone, potentiate s the clinical antidepressant properties of 5-HT reuptake inhibitors ( SSRIs). Herein, we examined the interaction of buspirone with two SSRI s, duloxetine and fluoxetine, on extracellular levels of 5-HT, dopamin e (DA), and noradrenaline (NAD) in single dialysate samples of freely moving rats. Duloxetine (5.0 mg/kg, s.c.) and fluoxetine (10.0 mg/kg, s.c.) increased dialysate levels of DA (65 and 60% vs. basal values, r espectively), NAD (400 and 90%, respectively), and 5-HT (130 and 110%, respectively) in the frontal cortex (FCX). Buspirone (2.5 mg/kg, s.c. ) similarly elevated levels of DA (100%) and NAD (160%) but reduced th ose of 5-HT (-50%). Administered with buspirone, the ability of duloxe tine and fluoxetine to increase 5-HT levels was transiently inhibited (over 60 min), although by the end of sampling (180 min) their actions were fully expressed. In contrast, buspirone markedly and synergistic ally facilitated the elevation in DA levels elicited by duloxetine (55 0%) and fluoxetine (240%). Furthermore, buspirone potentiated the indu ction of NAD levels by duloxetine (750%) and fluoxetine (350%). These data suggest that a reinforcement in the influence of SSRIs on DA and, possibly, NAD but not 5-HT release in FCX may contribute to their inc reased antidepressant activity in the presence of buspirone. More gene rally, they support the hypothesis that a reinforcement in dopaminergi c transmission in the FCX contributes to the actions of SSRIs and othe r antidepressant drugs.