Murphy James M, Stewart Robert B, Bell Richard L, Badia-Elder Nancy E, Carr Lucinda G, McBride William J, Lumeng Lawrence, Li Ting-Kai
Department of Psychology, Purdue School of Science, Indiana University--Purdue University Indianapolis, 46202-1375, USA.
Behav Genet. 2002 Sep;32(5):363-88. doi: 10.1023/a:1020266306135.
The Indiana lines of selected rats, the HAD and LAD replicates and the P and NP lines, were bred for high and low alcohol preference. The P and HAD lines have met criteria for an animal model of alcoholism in that they voluntarily consume sufficient ethanol to achieve significant blood alcohol concentrations, and their alcohol-seeking behavior is reinforced by the pharmacological effects of ethanol rather than its taste, caloric content, or other properties. These lines have been characterized extensively for associated behavioral and physiological phenotypes. The P and HAD rats show an enhanced responsiveness to the stimulatory effects of ethanol and reduced sensitivity to the aversive sedative effects of ethanol. Consistent findings with the selected lines include differences in the mesolimbic dopamine reward system, as well as differences in serotonin, GABA, endogenous opioid, and neuropeptide Y systems. Genetic mapping studies have identified quantitative trait loci influencing alcohol preference on chromosomes 3, 4, and 8 in the inbred P/NP rats and on chromosomes 5, 10, 12, and 16 in the noninbred HAD1/LAD1 rats. The elucidation of the genotypes and phenotypes that result in excessive alcohol intake may lead to a better understanding of alcohol abuse and alcoholism and could guide strategies for potential treatment and prevention.
选用的大鼠印第安纳品系、HAD和LAD重复品系以及P和NP品系,是针对高酒精偏好和低酒精偏好进行培育的。P和HAD品系符合酒精中毒动物模型的标准,因为它们会自愿摄入足够的乙醇以达到显著的血液酒精浓度,并且它们对酒精的寻求行为是由乙醇的药理作用而非其味道、热量或其他特性强化的。这些品系已针对相关的行为和生理表型进行了广泛的特征描述。P和HAD大鼠对乙醇的刺激作用反应增强,对乙醇的厌恶镇静作用敏感性降低。所选品系的一致发现包括中脑边缘多巴胺奖赏系统的差异,以及血清素、γ-氨基丁酸、内源性阿片肽和神经肽Y系统的差异。基因定位研究已经确定了影响近交P/NP大鼠3号、4号和8号染色体以及非近交HAD1/LAD1大鼠5号、10号、12号和16号染色体上酒精偏好的数量性状位点。对导致过度饮酒的基因型和表型的阐明可能会更好地理解酒精滥用和酒精中毒,并可为潜在的治疗和预防策略提供指导。