Selective antagonism at dopamine D3 receptors prevents nicotine-triggered relapse to nicotine-seeking behavior

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 D-3 receptors. As such, the present study aimed at investigating the effect of the selective D-3 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 D-3 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 D-3 receptor antagonists for the pharmacotherapeutic management of relapse to drug-seeking behaviors.