SEROTONIN1B RECEPTORS IN THE VENTRAL TEGMENTAL AREA MODULATE COCAINE-INDUCED INCREASES IN NUCLEUS ACCUMBENS DOPAMINE LEVELS
O'Dell LE, Parsons LH.
THE SCRIPPS RESEARCH INSTITUTE.
J Pharmacol Exp Ther. 2004 Jun 28
ABSTRACTPrevious work has demonstrated that peripheral serotonin1B (5-HT1B) receptor agonist administration facilitates the behavioral and neurochemical effects of cocaine. This study employed dual probe microdialysis to investigate whether activation of serotonin1B (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 CP 93,129 by reverse dialysis produced a dose-dependent (30 and 100 micro M) potentiation of cocaine-induced (10 mg/kg, i.p.) increases in NAcc DA efflux, and concurrent cocaine-induced decreases in VTA gamma-aminobutyric acid (GABA) efflux. There was no effect of either local CP 93,129 or peripheral cocaine on VTA glutamate (GLU) efflux. Intra-VTA administration of the 5-HT1A/7 receptor agonist 8-OH-DPAT (100 micro M) 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 micro M) on both cocaine-induced increases in NAcc DA levels and cocaine-induced decreases in VTA GABA levels were reversed by co-administration of the selective 5-HT1B receptor antagonist GR 55562 (300 micro M). 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.5-HT3
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