Addiction Biology Unit, Section for Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Brain Res. 2009 Dec 11;1305 Suppl:S27-36. doi: 10.1016/j.brainres.2009.09.053. Epub 2009 Sep 23.
Ethanol is known to directly interact with the glycine receptor (GlyR). GlyRs are membrane proteins and are constituted as either alpha-homomers or alpha-beta heteromers with a subunit stoichiometry of 2 alpha 3 beta. Previous studies by our group have suggested a role for GlyRs and its endogenous ligands glycine and taurine in the mesolimbic dopamine activating and reinforcing effects of ethanol. Here we use quantitative PCR (qPCR) to compare the relative GlyR expression in Alko Alcohol/Non-Alcohol (AA/ANA) rats. These animals have been selectively bred to create distinct populations regarding alcohol consumption and preference, presumably mainly due to genetic differences. The aim of this study was to examine the relative gene expression of GlyR subunits (alpha1-3 and beta) in different brain areas and relate it to alcohol consumption. The hypothesis was that AA/ANA rats are differently disposed to ethanol consumption due to their GlyR set-ups and/or compositions. Results from the present study indicate that alpha2 is the most widely expressed alpha-subunit in the forebrain regions and that the alpha 2 beta-heteromer seems to be the most common subunit composition in this part of the CNS. Despite displaying different drinking behaviours the anticipated differences in mRNA expression were few. However, correlations found between alcohol consumption and/or preference and GlyR expression support a role for GlyRs in alcohol consumption. Tentative differences between AA and ANA animals related to GlyR transmission could therefore lie in, for example, the regulation of the levels of the endogenous ligand(s) for the receptor or in mechanisms downstream to GlyR activation.
乙醇已知直接与甘氨酸受体（GlyR）相互作用。GlyRs 是膜蛋白，由α-同聚物或α-β异源二聚体组成，亚基比例为 2α3β。我们小组的先前研究表明，GlyRs 及其内源性配体甘氨酸和牛磺酸在乙醇的中脑边缘多巴胺激活和强化作用中起作用。在这里，我们使用定量 PCR（qPCR）比较 Alko Alcohol/Non-Alcohol（AA/ANA）大鼠中的相对 GlyR 表达。这些动物经过选择性繁殖，形成了关于饮酒和偏好的不同群体，这主要归因于遗传差异。本研究的目的是检查不同脑区中 GlyR 亚基（α1-3 和β）的相对基因表达，并将其与饮酒行为相关联。假设是，由于 AA/ANA 大鼠的 GlyR 结构和/或组成，它们对乙醇的摄取有不同的倾向。本研究的结果表明，α2 是前脑区域表达最广泛的α亚基，并且α2β-异源二聚体似乎是 CNS 这部分最常见的亚基组成。尽管表现出不同的饮酒行为，但预期的 mRNA 表达差异很少。然而，在饮酒行为之间发现的相关性和/或偏好与 GlyR 表达之间的相关性支持 GlyRs 在饮酒行为中的作用。因此，与 GlyR 传递有关的 AA 和 ANA 动物之间的暂定差异可能在于，例如，受体的内源性配体（s）的水平的调节或 GlyR 激活后的下游机制。
