Cunningham C L
Department of Medical Psychology, Oregon Health Sciences University, Portland 97201-3098, USA.
Psychopharmacology (Berl). 1995 Jul;120(1):28-41. doi: 10.1007/BF02246142.
Genetic differences in ethanol's ability to induce conditioned place preference were studied in 20 BXD Recombinant Inbred (RI) mouse strains and in the C57BL/6J and DBA/2J progenitor strains. Male mice from each strain were exposed to a Pavlovian conditioning procedure in which a distinctive floor stimulus (CS+) was paired four times with ethanol (2 g/kg). A different floor stimulus (CS-) was paired with saline. Control mice were injected only with saline. Floor preference testing without ethanol revealed significant genetic differences in conditioned place preference, with some strains spending nearly 80% time on the ethanol-paired floor while others spent only 50% (i.e., no preference). Control mice showed genetic differences in unconditioned preference for the floor cues, but unconditioned preference was not genetically correlated with conditioned preference. There were also substantial genetic differences in ethanol-stimulated activity, but contrary to psychomotor stimulant theory, ethanol-induced activity on conditioning trials was not positively correlated with strength of conditioned place preference. However, there was a significant negative genetic correlation (r = -0.42) between test session activity and preference. Quantitative trait loci (QTL) analyses showed strong associations (P < 0.01) between conditioned place preference and marker loci on chromosomes 4, 8, 9, 18 and 19. Weaker associations (0.01 < P < 0.05) were identified on several other chromosomes. Analysis also yielded several significant QTL for unconditioned preference, ethanol-stimulated activity, and sensitization. Overall, these data support the conclusion that genotype influences ethanol-induced conditioned place preference, presumably via genetic differences in sensitivity to ethanol's rewarding effects. Moreover, several chromosomal regions containing candidate genes of potential relevance to ethanol-induced conditioned place preference have been identified.
在20个BXD重组近交（RI）小鼠品系以及C57BL/6J和DBA/2J祖系品系中研究了乙醇诱导条件性位置偏好能力的遗传差异。每个品系的雄性小鼠都接受了巴甫洛夫条件反射程序，其中一种独特的地面刺激（CS+）与乙醇（2 g/kg）配对四次。另一种不同的地面刺激（CS-）与生理盐水配对。对照小鼠仅注射生理盐水。在没有乙醇的情况下进行的地面偏好测试显示，条件性位置偏好存在显著的遗传差异，一些品系在与乙醇配对的地面上花费近80%的时间，而其他品系仅花费50%（即无偏好）。对照小鼠在对地面线索的非条件性偏好方面表现出遗传差异，但非条件性偏好与条件性偏好没有遗传相关性。乙醇刺激的活动也存在显著的遗传差异，但与精神运动兴奋剂理论相反，乙醇在条件反射试验中诱导的活动与条件性位置偏好的强度没有正相关。然而，测试阶段的活动与偏好之间存在显著的负遗传相关性（r = -0.42）。数量性状基因座（QTL）分析表明，条件性位置偏好与4号、8号、9号、18号和19号染色体上的标记基因座之间存在强关联（P < 0.01）。在其他几条染色体上也发现了较弱的关联（0.01 < P < 0.05）。分析还产生了几个与非条件性偏好、乙醇刺激的活动和敏化相关的显著QTL。总体而言，这些数据支持以下结论：基因型影响乙醇诱导的条件性位置偏好，大概是通过对乙醇奖赏效应敏感性的遗传差异。此外，已经确定了几个含有与乙醇诱导的条件性位置偏好潜在相关候选基因的染色体区域。
