Continuous cocaine treatment and monoamine transmission measured by microdialysis in the rat ventral tegmental area

Rats were treated on a continuous cocaine administration schedule (85 mumol/kg/day s.c. by osmotic minipumps for 2 weeks followed by a 1-week drug-free period) that makes them tolerant to the locomotor-activating effect of cocaine. Subsequently, extracellular serotonin (5-HT) and dopamine (DA) were assayed in the ventral tegmental area (VTA) by microdialysis in the awake animal. Local infusion of the 5-HT 1A, B, D, 2, 6, 7 receptor antagonist methiothepin (50 muM for 3 hours) into the VTA caused a smaller increase in dialysate 5-HT in cocaine- than saline-pretreated rats (902±189 versus 1630±210%; area under the curve, p<0.02), whereas the increase in DA was small and unchanged (281±50 versus 290±76%; area under the curve, p=0.09). The results provide preliminary support for a cocaine-induced subsensitivity of 5-HT 1B autoreceptors in the VTA in agreement with our previous results obtained ex vivo.