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

被引：115

作者：

Andreoli, M ^{[1
]}

Tessari, M ^{[1
]}

Pilla, M ^{[1
]}

Valerio, E ^{[1
]}

Hagan, JJ ^{[1
]}

Heidbreder, CA ^{[1
]}

机构：

[1] GlaxoSmithKline, Ctr Excellence Drug Discovery Psychiat, Dept Drug Dependence & Behav Neurochem, I-37135 Verona, Italy

来源：

NEUROPSYCHOPHARMACOLOGY | 2003年 / 28卷 / 07期

关键词：

self-administration; drug dependence; nicotine; relapse; dopamine receptors;

D O I：

10.1038/sj.npp.1300183

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：1272 / 1280

页数：9

共 93 条

[11] Role of dopamine D2-like receptors in cocaine self-administration: Studies with D2 receptor mutant mice and novel D2 receptor antagonists [J].