Motivational state determines the functional role of the mesolimbic dopamine system in the mediation of opiate reward processes
Motivational state determines the functional role of the mesolimbic dopamine system in the mediation of opiate reward processes
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DOI：
10.1016/s0166-4328(01)00327-8
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发表时间：
2002-02-01
影响因子：
2.7
通讯作者：
van der Kooy, D
中科院分区：
文献类型：
--
作者：
Laviolette, SR;Nader, K;van der Kooy, D
我们之前已经报道，只有在阿片依赖和戒断状态下，中脑边缘多巴胺(DA)底物才与阿片类药物的奖赏效应密切相关。然而，在以前药物幼稚的动物中，阿片奖励是通过DA不依赖的神经系统来调节的。在本研究中，我们报道了双侧伏核(NAC)微量注射DA受体拮抗剂α-氟苯硫醇(0.3-3mug/0.5mul)，阻断吗啡奖赏(10 mg/kg，i.p.)。在阿片戒断的动物中，但在阿片幼稚的动物中不是，这表明在剥夺药物的激励状态中，阿片奖励信号需要伏隔多巴胺受体。接下来，研究了多巴胺在阿片类药物依赖和躯体戒断以及戒断厌恶情绪表达中的作用。预先注射α-氟苯硫醇(0.8 mg/kg，i.p)。吗啡注射前阿片类药物依赖发展过程中不影响戒断厌恶的表达，也不影响躯体戒断的表达。我们以前曾报道，用多巴胺受体拮抗剂a-flupenthixol预处理，可以阻断阿片类药物戒断的不良影响。我们现在报告用直接的多巴胺受体激动剂阿朴吗啡(1.0-5.0 mg/kg，i.p.)预处理。在戒断状态下进行条件反射之前，也可以阻止阿片类药物戒断的不良影响。我们认为，阿片类药物戒断的厌恶动机效应可能是由特定的多巴胺能神经元信号介导的。(C)2002 Elsevier Science B.V.保留所有权利。
We have previously reported that mesolimbic dopamine (DA) substrates are critically involved in the rewarding effects of opiates only during states of opiate-dependence and withdrawal. However, in previously drug-naive animals, opiate reward is mediated through a DA-independent neural system. In the present study, we report that bilateral microinjections of a DA receptor antagonist, a-flupenthixol (0.3-3 mug/0.5 mul) into the nucleus accumbens (NAc), blocks morphine reward (10 mg/kg, i.p.) in opiate-withdrawn animals, but not in opiate-naive animals, suggesting that accumbal dopamine receptors are required for opiate reward signaling in drug-deprived motivational states. Next, the role of dopamine was examined in the development of opiate dependence and somatic withdrawal, and expression of withdrawal aversions. Pretreatment with a-flupenthixol (0.8 mg/kg, i.p.) before morphine injections during the development of opiate dependence did not effect expression of withdrawal aversions or the expression of somatic withdrawal. We have previously reported that pretreatment with a dopamine receptor antagonist, a-flupenthixol, blocks the aversive effects of opiate withdrawal. We now report that pretreatment with a direct dopamine receptor agonist, apomorphine (1.0-5.0 mg/kg, i.p.) before conditioning in a state of withdrawal, also blocks the aversive effects of opiate withdrawal. We propose that the aversive motivational effects of opiate withdrawal may be mediated by a specific dopaminergic neuronal signal. (C) 2002 Elsevier Science B.V. All rights reserved.