Fadda P, Tronci S, Colombo G, Fratta W
Department of Neuroscience, University of Cagliari, Italy.
Alcohol Clin Exp Res. 1999 Aug;23(8):1296-305.
Previous studies have suggested that alcohol-reinforcing effects are mediated by the endogenous opioid system, which, in turn, stimulates mesolimbic dopaminergic neurotransmission. In addition, evidence obtained in both humans and rats indicates that genetic factors may influence alcohol-drinking behavior. In the present study, we examined several components of the opioid system in selected brain regions of rats bred selectively for their innate alcohol preference (Sardinian preferring = sP) or alcohol aversion (Sardinian nonpreferring = sNP).
To evaluate whether differences observed were consequent to alcohol intake, sP rats were divided into two subgroups, ethanol-naive sP (sP) and ethanol-experienced sP (sPexp). Opioid receptors were labeled, using [3H]naloxone (mu, delta, and kappa receptors), [D-Ala2,N-Me-Phe4,Gly,ol5]enkephalin ([3H]DAMGO; mu receptors), and [D-Ala2,D-Leu5]enkephalin ([3H]DADLE; delta receptors), by means of quantitative autoradiography. Enkephalin and dynorphin mRNA contents were measured by in situ hybridization by using 25- and 47-base oligonucleotide probes with sequences complementary to mRNA encoding rat enkephalin or dynorphin.
Our results revealed a significant reduction of opioid receptors in caudate-putamen nucleus and in the shell portion of the nucleus accumbens in sP compared with sNP rats. Alcohol intake partially reversed this reduction in the caudate-putamen nucleus. In addition, enkephalin mRNA expression was found to be decreased in the ventral part of caudate-putamen nucleus and increased in the cerebral cortex of sP rats compared with sNP rats; no significant differences were found in dynorphin mRNA expression in any of the brain areas examined.
Differences observed between the two lines of rats may implicate that genetic modifications in the opioid system are possibly responsible for the innate preference of sP rats toward alcohol intake. At the same time, it cannot be excluded that other functions might also be affected to some degree.
先前的研究表明，酒精强化效应是由内源性阿片系统介导的，而内源性阿片系统反过来又会刺激中脑边缘多巴胺能神经传递。此外，在人类和大鼠身上获得的证据表明，遗传因素可能会影响饮酒行为。在本研究中，我们检查了选择性培育出具有先天酒精偏好（撒丁岛偏好型 = sP）或酒精厌恶（撒丁岛非偏好型 = sNP）的大鼠特定脑区中阿片系统的几个组成部分。
为了评估观察到的差异是否是由酒精摄入导致的，将 sP 大鼠分为两个亚组，即未接触过乙醇的 sP（sP）和接触过乙醇的 sP（sPexp）。使用[³H]纳洛酮（μ、δ和κ受体）、[D - Ala²，N - Me - Phe⁴，Gly - ol⁵]脑啡肽（[³H]DAMGO；μ受体）和[D - Ala²，D - Leu⁵]脑啡肽（[³H]DADLE；δ受体），通过定量放射自显影法标记阿片受体。使用与编码大鼠脑啡肽或强啡肽的mRNA序列互补的25个碱基和47个碱基的寡核苷酸探针，通过原位杂交法测量脑啡肽和强啡肽mRNA的含量。
我们的结果显示，与 sNP 大鼠相比，sP 大鼠尾状核 - 壳核和伏隔核壳部的阿片受体显著减少。酒精摄入部分逆转了尾状核 - 壳核中的这种减少。此外，与 sNP 大鼠相比，发现 sP 大鼠尾状核 - 壳核腹侧部分的脑啡肽mRNA表达降低，而大脑皮层中的表达增加；在所检查的任何脑区中，强啡肽mRNA表达均未发现显著差异。
在这两种大鼠品系之间观察到的差异可能意味着阿片系统中的基因改变可能是 sP 大鼠对酒精摄入具有先天偏好的原因。同时，也不能排除其他功能可能在某种程度上也受到影响。
