Serotonin1B receptors in the ventral tegmental area modulate cocaine-induced increases in nucleus accumbens dopamine levels

Previous work has demonstrated that peripheral serotonin(1B) (5-HT1B) receptor agonist administration facilitates the behavioral and neurochemical effects of cocaine. This study used dual probe microdialysis to investigate whether activation of serotonin(1B) (5-HT1B) receptors in the ventral tegmental area (VTA) alters the ability of peripherally administered cocaine to elevate dopamine (DA) levels in the ipsilateral nucleus accumbens (NAcc) of drug-naive Wistar rats. Intra-VTA administration of the selective 5-HT1B agonist 1,4-dihydro-3-(1,2,3,6-tetrahydro-4- pyridinyl)-5H-pyrrolo [3,2-b] pyridin-5-one dihydrochloride (CP 93,129) by reverse dialysis produced a dose-dependent ( 30 and 100 muM) potentiation of cocaine-induced ( 10 mg/kg i.p.) increases in NAcc DA efflux and concurrent cocaine-induced decreases in VTA GABA efflux. There was no effect of either local CP 93,129 or peripheral cocaine on VTA glutamate efflux. Intra-VTA administration of the 5-HT1A/7 receptor agonist 8-hydroxy-2-dipropylaminotetralin (8-OH- DPAT; 100 muM) did not alter cocaine-induced alterations in NAcc DA or VTA GABA, suggesting that the effects of CP 93,129 were not mediated through 5-HT1A receptors. Moreover, the effects of intra-VTA CP 93,129 ( 100 muM) on both cocaine-induced increases in NAcc DA levels and cocaine-induced decreases in VTA GABA levels were reversed by coadministration of the selective 5-HT1B receptor antagonist 3-[3-( dimethylamine) propyl]-4-hydroxy-N-[4( 4-pyridinyl] phenyl] benzamide dihydrochloride (GR 55562; 300 muM). In the absence of cocaine, intra-VTA CP 93,139 produced an increase in NAcc DA and decrease in VTA GABA levels. However, intra-VTA GR 55562 alone had no effect on any of our neurochemical measures. These findings indicate that activation of VTA 5-HT1B receptors potentiates cocaine-induced increases in NAcc DA levels by enhancing the ability of cocaine to decrease VTA GABA efflux.