¹Center of Excellence for Drug Discovery in Psychiatry, GlaxoSmithKline Pharmaceuticals, Via A. Fleming 4, 37135 Verona, Italy

Correspondence: Dr CA Heidbreder, Department of Drug Dependence & Behavioral Neurochemistry, Center of Excellence for Drug Discovery in Psychiatry, GlaxoSmithKline Pharmaceuticals, Via A. Fleming 4, 37135 Verona, Italy. Tel: +39 045 921 9769; Fax: +39 045 921 8047; E-mail: Christian_A_Heidbreder@gsk.com

Received 2 August 2002; Revised 6 February 2003; Accepted 7 February 2003; Published online 16 April 2003.

Abstract

Drugs of abuse, including, nicotine have been shown to enhance brain reward functions in the mesocortico-limbic dopamine (DA) system in general, and the nucleus accumbens in particular. The latter occupies a prominent position in the ventral striatum and expresses a high density of DA D₃ receptors. As such, the present study aimed at investigating the effect of the selective D₃ receptor antagonist SB-277011-A on both the stable maintenance of intravenous nicotine self-administration and nicotine-triggered relapse to nicotine-seeking behavior in the rat. SB-277011-A (3–10 mg/kg i.p.) significantly reduced reinstatement of nicotine-seeking behavior without affecting nicotine self-administration per se. These results suggest that DA D₃ receptors are involved in the reinstatement of nicotine-seeking behavior independently of any interaction with the primary reinforcing effects of nicotine itself. These findings point toward the potential use of selective DA D₃ receptor antagonists for the pharmacotherapeutic management of relapse to drug-seeking behaviors.