||RATIONALE: Experimental evidence indicates that the mesolimbic dopamine (DA) pathway innervating the ventral striatum is critically involved in the motivational effects of drug abuse. However, the role of DA transmission of the two main subdivisions of the nucleus accumbens (NAc), the shell and the core, in the motivational properties of nicotine is unknown. OBJECTIVES: The aim of this study was to investigate the role of DA D1 and D2 receptors of the rat NAc shell and core in the motivational effects of nicotine using a conditioned place preference (CPP) paradigm. METHODS: The effect of the intracerebral infusion of DA antagonists specific for DA D1 (SCH 39166) and D2 receptors (L-sulpiride) was studied in a single-trial place-conditioning paradigm with fixed assignment of the drug to the unpreferred compartment. RESULTS: Nicotine induced significant CPP at the dose of 0.4 and 0.6 mg/kg subcutaneously (s.c.). Intra-NAc shell infusion of SCH 39166 (6.25, 12.5, 25 and 50 ng bilaterally, 10 min before nicotine administration), impaired in a dose-dependent manner the acquisition of CPP by nicotine (0.4 mg/kg s.c.). SCH 39166 failed to affect nicotine CPP when infused into the NAc core. L-sulpiride (25 and 50 ng bilaterally) had no effect on acquisition after intra-Nac shell infusion. SCH 39166 and L-sulpiride were ineffective after infusion in the NAc shell and core 10 min before the test session. CONCLUSIONS: The results indicate that dopamine D1 but not D2 receptors of the NAc shell are specifically involved in the acquisition of nicotine-induced CPP.