Translational Addiction Research Laboratory, Centre for Addiction and Mental Health, Toronto, Canada.
Int J Neuropsychopharmacol. 2010 Mar;13(2):181-90. doi: 10.1017/S1461145709991064. Epub 2009 Dec 9.
The dopamine D3 receptor (DRD3) has been suggested to be involved in the mechanisms underlying stimulus-controlled drug-seeking behaviour. Ligands acting as DRD3 antagonists (SB 277011-A) or DRD3 partial agonists (BP 897) have shown some promise for reducing the influence of drug-associated cues on motivational behaviour. Here, effects of SB 277011-A and BP 897 were evaluated on cue-induced reinstatement of nicotine-seeking in rats. The effects of BP 897 on nicotine self-administration under a fixed-ratio 5 (FR5) schedule of reinforcement were also evaluated. SB 277011-A (1-10 mg/kg) was able to block cue-induced reinstatement of nicotine-seeking, indicating that DRD3 selective antagonism may be an effective approach to prevent relapse for nicotine. In contrast, BP 897 did not block the cue-induced reinstatement of nicotine-seeking or nicotine-taking under the FR5 schedule. In a control study, rats did not respond to the light stimuli without nicotine delivery, indicating that the responding for the drug-associated cues was induced by the previous pairing of light stimuli with nicotine's effects. These findings validate the role of DRD3 on reactivity to drug-associated stimuli and suggest that the DRD3 antagonist, but perhaps not the DRD3 partial agonist, could be used to prevent relapse in tobacco smokers.
多巴胺 D3 受体（DRD3）被认为参与了刺激控制药物寻求行为的机制。作为 DRD3 拮抗剂（SB 277011-A）或 DRD3 部分激动剂（BP 897）的配体在减少药物相关线索对动机行为的影响方面显示出了一些希望。在这里，评估了 SB 277011-A 和 BP 897 对尼古丁寻求的线索诱导复吸的影响。还评估了 BP 897 在固定比率 5（FR5）强化方案下对尼古丁自我给药的影响。SB 277011-A（1-10 mg/kg）能够阻断线索诱导的尼古丁寻求复吸，表明 DRD3 选择性拮抗可能是预防尼古丁复发的有效方法。相比之下，BP 897 不能阻断线索诱导的尼古丁寻求复吸或 FR5 方案下的尼古丁摄取。在一项对照研究中，没有尼古丁给药的老鼠对光刺激没有反应，这表明与药物相关的线索的反应是由先前的光刺激与尼古丁的作用配对引起的。这些发现验证了 DRD3 在对药物相关刺激的反应中的作用，并表明 DRD3 拮抗剂，但可能不是 DRD3 部分激动剂，可用于预防烟草使用者的复发。
