Acute administration of the selective D3 receptor antagonist SB-277011A blocks the acquisition and expression of the conditioned place preference response to heroin in male rats
Acute administration of the selective D3 receptor antagonist SB-277011A blocks the acquisition and expression of the conditioned place preference response to heroin in male rats
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DOI：
10.1002/syn.10188
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发表时间：
2003-06-01
期刊：
影响因子：
2.3
通讯作者：
Hagan, JJ
中科院分区：
文献类型：
--
作者：
Ashby, CR;Paul, M;Hagan, JJ
边缘脑区，如杏仁核和杏仁核，被认为在介导成瘾药物的作用中起作用（Gardner，1997）。这些边缘系统区域的多巴胺神经支配似乎与成瘾药物产生的奖励和/或激励动机有关（Berridge和罗宾逊，1998）。许多工作致力于多巴胺D1和D2受体在介导成瘾药物作用中的作用（Platt et al.，2002年）。然而，多巴胺D3受体和成瘾的关注较少，尽管在边缘脑位点中存在大量与成瘾有关的D3受体（Shafer和Levant，1998）。此外，D3受体在成瘾中的作用在很大程度上仍然不确定，这是由于缺乏与D2和其他神经递质受体相比对D3具有高选择性的化合物。最近，据报道，化合物SB-277011 A是一种有效的、脑渗透的和高选择性的D3受体拮抗剂（Reavill等人，2000; Stemp等人，2000年）。SB-277011 A对人和大鼠D3受体都具有高亲和力，其选择性是D2受体的100-150倍，并且与66种其他受体、酶和离子通道相比具有显著的选择性（Reavill等人，2000年）。我们之前已经表明，在雄性大鼠中急性全身施用SB-277011 A：1）阻断可卡因对电脑刺激奖赏的增强，2）剂量依赖性地减弱可卡因诱导的条件性位置偏爱（CPP），和3）剂量依赖性地减弱可卡因触发的可卡因寻求行为的恢复（Vorel等人，2002年）。此外，已经证明SB-277011 A减弱可卡因的次级强化性质（DiCiano等人，2002; Everitt等人，2001）和可卡因诱导的条件性活动过度（LeFoll等，为了将我们先前关于SB-277011 A的CPP发现扩展到阿片类成瘾药物，进行了本研究以检查SB-277011 A对雄性Sprague-Dawley大鼠中海洛因诱导的CPP反应的获得和表达的影响。
Limbic brain areas, such as the amygdala and nucleus accumbens, are believed to play a role in mediating the action of addictive drugs (Gardner, 1997). Dopamine innervation of these limbic areas appears to be involved in the reward and/or incentive motivation produced by addictive drugs (Berridge and Robinson, 1998). Much work has been devoted to the role of dopamine D1 and D2 receptors in mediating addictive drug action (Platt et al., 2002). However, less attention has been paid to the dopamine D3 receptor and addiction, despite significant D3 receptor presence in limbic brain loci implicated in addiction (Shafer and Levant, 1998). Moreover, the role of the D3 receptor in addiction remains largely undefined due to a lack of compounds with high selectivity for D3 compared to D2 and other neurotransmitter receptors. Recently, it has been reported that the compound SB-277011A is a potent, brain penetrant, and highly selective D3 receptor antagonist (Reavill et al., 2000; Stemp et al., 2000). SB-277011A has high affinity for both human and rat D3 receptors, with a 100–150-fold selectivity over D2 receptors and significant selectivity compared to 66 other receptors, enzymes, and ion channels (Reavill et al., 2000). We have previously shown that acute systemic administration of SB-277011A in male rats: 1) blocked cocaine’s enhancement of electrical brain-stimulation reward, 2) dose-dependently attenuated cocaine-induced conditioned place preference (CPP), and 3) dosedependently attenuated cocaine-triggered reinstatement of cocaine-seeking behavior (Vorel et al., 2002). Furthermore, it has been demonstrated that SB-277011A attenuates the secondary reinforcing properties of cocaine (DiCiano et al., 2002; Everitt et al., 2001) and cocaine-induced conditioned hyperactivity (LeFoll et al., 2002), suggesting that the D3 dopamine receptor plays a key role in mediating the control of drug-seeking behavior.In order to extend our previous CPP findings with SB-277011A to an addictive drug of the opiate class, the current study was undertaken to examine the effect of SB-277011A on the acquisition and expression of heroin-induced CPP response in male Sprague-Dawley rats.