Gremel Christina M, Cunningham Christopher L
Department of Behavioral Neuroscience, Portland Alcohol Research Center, Oregon Health & Science University, Portland, OR, USA.
Neuropsychopharmacology. 2009 May;34(6):1443-53. doi: 10.1038/npp.2008.179. Epub 2008 Oct 1.
Although progress has been made identifying neural mechanisms underlying ethanol's primary reinforcing effects, few studies have examined the mechanisms mediating ethanol-induced conditioned effects. A recent lesion study suggests that expression of ethanol-conditioned behaviors depends upon an intact amygdala and nucleus accumbens core. However, specific mechanisms within these nuclei are unknown. In the present experiments, we used site-specific microinfusions of dopamine and NMDA receptor antagonists to examine the roles of accumbens and amygdala in the expression of ethanol conditioned place preference (CPP) in mice. In experiments 1 and 2, a D1/D2/D3 receptor antagonist (flupenthixol) was infused into accumbens or amygdala before testing, whereas experiment 3 used pretest infusions of an NMDA antagonist (AP-5) to examine the role of intra-accumbens NMDA receptors. Dopamine antagonism of accumbens was without effect, but intra-amygdala infusions of flupenthixol blocked CPP expression. Moreover, this effect was dependent upon dopamine antagonism within the basolateral nucleus but not the central nucleus of the amygdala. Antagonism of NMDA receptors in accumbens also blocked CPP expression. The present findings suggest that expression of the ethanol-conditioned response depends upon amygdala dopamine and accumbens NMDA receptors. These are the first studies in any species to show a role for amygdala dopamine receptors and the first studies in mice to implicate accumbens NMDA receptors in ethanol-induced conditioned effects.
尽管在确定乙醇主要强化作用的神经机制方面已取得进展，但很少有研究探讨介导乙醇诱导的条件性效应的机制。最近的一项损伤研究表明，乙醇条件性行为的表达依赖于完整的杏仁核和伏隔核核心。然而，这些核内的具体机制尚不清楚。在本实验中，我们使用多巴胺和NMDA受体拮抗剂的位点特异性微量注射来研究伏隔核和杏仁核在小鼠乙醇条件性位置偏爱（CPP）表达中的作用。在实验1和2中，在测试前将D1/D2/D3受体拮抗剂（氟哌噻吨）注入伏隔核或杏仁核，而实验3使用NMDA拮抗剂（AP-5）的测试前注射来研究伏隔核内NMDA受体的作用。伏隔核的多巴胺拮抗作用无效，但杏仁核内注射氟哌噻吨可阻断CPP表达。此外，这种效应依赖于杏仁核基底外侧核而非中央核内的多巴胺拮抗作用。伏隔核内NMDA受体的拮抗作用也可阻断CPP表达。目前的研究结果表明，乙醇条件性反应的表达依赖于杏仁核多巴胺和伏隔核NMDA受体。这些是在任何物种中首次表明杏仁核多巴胺受体作用的研究，也是在小鼠中首次表明伏隔核NMDA受体与乙醇诱导的条件性效应有关的研究。
