1. ¹Unité Mixte de Recherche-Centre National de la Recherche Scientifique (UMR-CNRS) 5541, Université Victor Segalen Bordeaux 2, Bordeaux Cedex, France
2. ²Center for Addiction Research and Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, USA

Correspondence: Dr U Spampinato, ^*Université Victor Segalen Bordeaux 2, Center Recherche Inserm U862, Institut Francois Magendie, 146 rue Léo Saignât, B.P. 59, Bordeaux Cedex, 33076, France. Tel: +33 557 57 37 57; Fax: +33 557 57 36 69, E-mail: umberto.spampinato@bordeaux.inserm.fr

Received 13 October 2006; Revised 14 February 2007; Accepted 6 March 2007; Published online 11 April 2007.

Abstract

Stimulation of central serotonin2C receptor (5-HT_2CR) inhibits dopamine (DA)-dependent neurochemical and behavioral effects of cocaine, while 5-HT_2CRs locally expressed into the ventral tegmental area (VTA) and the nucleus accumbens (NAc) exert opposite functional control over cocaine-induced behavioral effects. Using in vivo microdialysis in halothane-anesthetized rats, we tested the hypothesis that this functionally opposite regulation of the mesoaccumbens DA pathway relies on the ability of 5-HT_2CRs in the VTA and the NAc to inhibit and enhance respectively cocaine-induced accumbal DA outflow. Intra-VTA injection of the 5-HT_2CR agonist Ro 60–0175 at 5 g/0.2 l, but not 1 g/0.2 l, attenuated the increase in accumbal DA outflow induced by the systemic administration of 10 mg/kg of cocaine. Intra-VTA injection of the 5-HT_2CR antagonist SB 242084 at either dose (0.1 or 0.5 g/0.2 l) did not modify the effects of cocaine. Intra-NAc application of Ro 60–0175 dose-dependently excited (0.1 M) and inhibited (1 M) cocaine-induced DA outflow. In contrast, intra-NAc application of SB 242084 resulted in diametrically opposite effects when applied at these concentrations. These results further support the idea that the overall action of central 5-HT_2CRs on accumbal DA output is dependent, at least in part, on the functional balance between different 5-HT_2CR populations within the NAc and within the mesoaccumbens DA pathway (VTA vs NAc).