Laviolette Steven R, Nader Karim, van der Kooy Derek
Department of Anatomy and Cell Biology, Neurobiology Research Group, University of Toronto, Medical Sciences Building, Toronto, Ont., Canada.
Behav Brain Res. 2002 Feb 1;129(1-2):17-29. doi: 10.1016/s0166-4328(01)00327-8.
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, alpha-flupenthixol (0.3-3 microg/0.5 microl) into the nucleus accumbens (NAc), blocks morphine reward (10 mg/kg, i.p.) in opiate-withdrawn animals, but not in opiate-naive animals, suggesting that accumbal dopamine receptors are required for opiate reward signaling in drug-deprived motivational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 alpha-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, alpha-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.
我们之前曾报道，中脑边缘多巴胺（DA）底物仅在阿片类药物依赖和戒断状态下才对阿片类药物的奖赏效应起关键作用。然而，在先前未接触过药物的动物中，阿片类药物奖赏是通过一个不依赖多巴胺的神经系统介导的。在本研究中，我们报告称，向伏隔核（NAc）双侧微量注射多巴胺受体拮抗剂阿立哌唑（0.3 - 3微克/0.5微升），可阻断阿片类药物戒断动物的吗啡奖赏（10毫克/千克，腹腔注射），但对未接触过阿片类药物的动物无效，这表明在药物剥夺的动机状态下，伏隔核多巴胺受体是阿片类药物奖赏信号传导所必需的。接下来，研究了多巴胺在阿片类药物依赖和躯体戒断发展以及戒断厌恶表达中的作用。在阿片类药物依赖发展过程中，在注射吗啡前用阿立哌唑（0.8毫克/千克，腹腔注射）预处理，并不影响戒断厌恶的表达或躯体戒断的表现。我们之前曾报道，用多巴胺受体拮抗剂阿立哌唑预处理可阻断阿片类药物戒断的厌恶效应。我们现在报告，在戒断状态下进行条件反射前，用直接多巴胺受体激动剂阿扑吗啡（1.0 - 5.0毫克/千克，腹腔注射）预处理，也可阻断阿片类药物戒断的厌恶效应。我们提出，阿片类药物戒断的厌恶动机效应可能由特定的多巴胺能神经元信号介导。
