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-HT(1B)) 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-HT(1B)) 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-HT(1B) 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 microM) 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-HT(1A/7) receptor agonist 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT; 100 microM) 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-HT(1A) receptors. Moreover, the effects of intra-VTA CP 93,129 (100 microM) 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-HT(1B) receptor antagonist 3-[3-(dimethylamine)propyl]-4-hydroxy-N-[4-(4-pyridinyl] phenyl] benzamide dihydrochloride (GR 55562; 300 microM). 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-HT(1B) receptors potentiates cocaine-induced increases in NAcc DA levels by enhancing the ability of cocaine to decrease VTA GABA efflux.
O'Dell
L E
LE
Department of Neuropharmacology, The Scripps Research Institute, CVN-7, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Parsons
L H
LH
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000378:metabolism*
D044302:Receptor, Serotonin, 5-HT1B; D018698:Glutamic Acid; D003042:Cocaine; D004298:Dopamine