Pharmacological actions of NGB 2904, a selective dopamine D3 receptor antagonist, in animal models of drug addiction.
Pharmacological actions of NGB 2904, a selective dopamine D3 receptor antagonist, in animal models of drug addiction.
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DOI：
10.1111/j.1527-3458.2007.00013.x
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发表时间：
2007-06
期刊：
影响因子：
--
通讯作者：
Z. Xi;E. Gardner
中科院分区：
文献类型：
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作者：
Z. Xi;E. Gardner
作为SB-277011A工作的继续，我们研究了另一种高选择性的多巴胺(DA)D3受体拮抗剂N-(4-[4-{2，3-dichlorophenyl}-1-piperazinyl]butyl)-2-fluorenylcarboxamide(NGB2904)在成瘾动物模型中的作用。我们的结果表明，NGB 2904通过全身给药抑制递增比率(PR)强化程序下维持的静脉注射可卡因自我给药，抑制可卡因或可卡因线索诱导的可卡因寻找行为的恢复，以及可卡因或其他成瘾药物增强的脑刺激奖赏(BSR)。NGB 2904对PR可卡因单次给药的作用持续时间较长(1-2天)，支持其在可卡因成瘾治疗中的潜在应用。在BSR范式中，NGB 2904对NGB 2904和可卡因的作用都是剂量依赖的；即，只有较低剂量的NGB 2904有效，其假定的抗成瘾作用可以通过增加可卡因或其他成瘾药物的剂量来克服。在这些药物成瘾动物模型中，提出了多巴胺依赖机制来解释NGB 2904对可卡因作用的影响。本文综述的数据表明，NGB 2904或其他D3选择性拮抗剂可能在控制吸毒行为或重新吸毒行为的动机方面具有潜力，但在对抗可卡因或其他成瘾药物产生的急性奖赏效应方面可能作用有限。此外，NGB 2904也可能成为研究D3受体在药物成瘾中作用的有用工具。
As a continuation of our work with SB-277011A, we have examined the effects of another highly elective dopamine (DA) D3 receptor antagonist, N-(4-[4-{2,3-dichlorophenyl}-1-piperazinyl]butyl)-2-fluorenylcarboxamide (NGB 2904), in animal models of addiction. Our results indicate that by systemic administration, NGB 2904 inhibits intravenous cocaine self-administration maintained under a progressive-ratio (PR) reinforcement schedule, cocaine- or cocaine cue-induced reinstatement of cocaine-seeking behavior, and cocaine- or other addictive drug-enhanced brain stimulation reward (BSR). The action of NGB 2904 on PR cocaine self-administration was long-lasting (1-2 days) after a single injection, supporting its potential use in treatment of cocaine addiction. The effects of NGB 2904 in the BSR paradigm were dose-dependent for both NGB 2904 and cocaine; that is, only lower doses of NGB 2904 were effective, and their putative antiaddiction effect could be overcome by increasing the doses of cocaine or other addictive drugs. A dopamine-dependent mechanism is proposed to explain the effects of NGB 2904 on cocaine's actions in these animal models of drug addiction. The data reviewed in this paper suggest that NGB 2904 or other D3-selective antagonists may have potential in controlling motivation for drug-taking behavior or relapse to drug-seeking behavior, but may have a limited role in antagonizing the acute rewarding effects produced by cocaine or other addictive drugs. In addition, NGB 2904 may also act as a useful tool to study the role of D3 receptors in drug addiction.