在为高酒精偏好或低酒精偏好而选择性培育的复制小鼠品系中，基线时以及急性酒精戒断期间的听觉惊吓反应。
Acoustic startle at baseline and during acute alcohol withdrawal in replicate mouse lines selectively bred for high or low alcohol preference.
作者信息
Chester Julia A, Barrenha Gustavo D
机构信息
Department of Psychological Sciences, Purdue University, West Lafayette, Indiana 47907-2081, USA.
出版信息
Alcohol Clin Exp Res. 2007 Oct;31(10):1633-44. doi: 10.1111/j.1530-0277.2007.00462.x.
BACKGROUND
Previous data in both rat and mouse genetic models suggest that there is a genetic relationship between acute alcohol withdrawal responses and innate alcohol drinking behavior. The purpose of the present study was to examine whether acute alcohol withdrawal responses, as measured by acoustic startle and prepulse inhibition (PPI) of acoustic startle, may be genetically related to innate differences in alcohol preference in 2 mouse lines selectively bred for high (HAP1 and HAP2) or low (LAP1 and LAP2) alcohol preference. Line differences in startle responses at baseline, prior to alcohol or saline treatment, were also measured.
METHODS
Alcohol-naive, male and female HAP1 (n = 35) and LAP1 (n = 32) and HAP2 (n = 43) and LAP2 (n = 40) mice were tested under baseline conditions and during withdrawal from a single injection of 4.0 g/kg alcohol or equal volume of saline at 4, 8, and 12 hours post-injection.
RESULTS
On most trial types, baseline startle responses and PPI were greater in both HAP lines than in both LAP lines, and startle responses were greater in males than in females. During acute alcohol withdrawal, both male LAP lines, and LAP1 females, showed reduced startle responses at the 4-hour time point during acute alcohol withdrawal. In contrast, both HAP1 males and females showed a trend toward enhanced startle at 4 hours in withdrawal. No clear differences in PPI during withdrawal were evident.
CONCLUSIONS
These findings indicate good evidence for a genetic relationship between greater baseline acoustic startle responses and PPI and high alcohol preference. Modest support for a genetic correlation between low alcohol preference and reduced startle responses at 4 hours in withdrawal was found in male mice. The suppression in acoustic startle during acute alcohol withdrawal in male LAP lines but not in male HAP lines suggests that a genetic propensity toward low alcohol preference may be related to greater sensitivity to alcohol as measured by acoustic startle responses during acute alcohol withdrawal.
背景
以往在大鼠和小鼠遗传模型中的数据表明，急性酒精戒断反应与先天性饮酒行为之间存在遗传关系。本研究的目的是检验通过听觉惊吓和听觉惊吓的前脉冲抑制（PPI）所测量的急性酒精戒断反应是否可能与两种为高（HAP1和HAP2）或低（LAP1和LAP2）酒精偏好而选择性培育的小鼠品系中酒精偏好的先天性差异存在遗传关系。还测量了在酒精或生理盐水处理之前基线时惊吓反应的品系差异。
方法
对未接触过酒精的雄性和雌性HAP1（n = 35）、LAP1（n = 32）、HAP2（n = 43）和LAP2（n = 40）小鼠在基线条件下以及在单次注射4.0 g/kg酒精或等量生理盐水后的4、8和12小时撤药期间进行测试。
结果
在大多数试验类型中，两个HAP品系的基线惊吓反应和PPI均高于两个LAP品系，并且雄性的惊吓反应大于雌性。在急性酒精戒断期间，两个雄性LAP品系以及LAP1雌性在急性酒精戒断的4小时时间点惊吓反应降低。相比之下，HAP1雄性和雌性在撤药4小时时均呈现惊吓增强的趋势。戒断期间PPI没有明显差异。
结论
这些发现为更高的基线听觉惊吓反应和PPI与高酒精偏好之间的遗传关系提供了充分证据。在雄性小鼠中发现了低酒精偏好与撤药4小时时惊吓反应降低之间存在遗传相关性的适度支持。雄性LAP品系而非雄性HAP品系在急性酒精戒断期间听觉惊吓的抑制表明，低酒精偏好的遗传倾向可能与急性酒精戒断期间通过听觉惊吓反应测量的对酒精更高的敏感性有关。
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