Selective antagonism at dopamine D3 receptors prevents nicotine-triggered relapse to nicotine-seeking behavior
Selective antagonism at dopamine D3 receptors prevents nicotine-triggered relapse to nicotine-seeking behavior
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DOI：
10.1038/sj.npp.1300183
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发表时间：
2003-07-01
影响因子：
7.6
通讯作者：
Heidbreder, CA
中科院分区：
文献类型：
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作者：
Andreoli, M;Tessari, M;Heidbreder, CA
包括尼古丁在内的滥用药物已被证明可以增强中皮质-边缘多巴胺（DA）系统的大脑奖励功能，尤其是伏隔核。后者在腹侧纹状体中占据突出位置，并表达高密度的DA D-3受体。因此，本研究旨在研究选择性D-3受体拮抗剂SB-277011 -A对大鼠静脉内尼古丁自我给药的稳定维持和尼古丁触发的尼古丁寻求行为复发的影响。SB-277011-A（3-10 mg/kg i.p.）显著减少尼古丁寻求行为的恢复，而不影响尼古丁自身给药。这些结果表明，DA D-3受体参与尼古丁寻求行为的恢复，独立于与尼古丁本身的主要强化作用的任何相互作用。这些研究结果指向潜在的使用选择性DA D-3受体拮抗剂的药物治疗管理复发的药物寻求行为。
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.