Chester Julia A, Blose Annette M, Froehlich Janice C
Department of Psychological Sciences, Purdue University, 703 Third Street, West Lafayette, IN 47907-2081, USA.
Alcohol Alcohol. 2005 Sep-Oct;40(5):379-87. doi: 10.1093/alcalc/agh172. Epub 2005 Jun 6.
The purpose of the present study is to determine whether the inverse genetic association between alcohol withdrawal magnitude and genetic propensity for alcohol drinking that we have previously identified in alcohol-naive rats given alcohol acutely, would also be seen following chronic alcohol exposure. The effect of forced, chronic alcohol treatment on subsequent voluntary alcohol drinking was also examined.
Male rats from the high alcohol drinking (HAD2) and low alcohol drinking (LAD2) lines received two intragastric (IG) infusions of alcohol (3.0 g/kg BW; 25% v/v) or an equal volume of water, separated by 5 h, every day for 20 consecutive days (chronic alcohol treatment). Acoustic startle reactivity was assessed at 10, 14, and 18 h after the second infusion on days 1, 5, 10, 15, and 20. After acoustic startle testing was completed, all rats received two IG infusions of 3.0 g alcohol/kg BW, separated by 5 h, and blood alcohol content was assessed at 10, 14, and 18 h after the second alcohol infusion. All rats were then given a 24 h free-choice between alcohol and water for 8 weeks.
Startle magnitude to a 120 dB tone was suppressed during alcohol withdrawal in both alcohol-treated HAD2 and LAD2 rats after 5, 10, and 15 days of alcohol treatment. Forced, chronic alcohol treatment produced metabolic tolerance in both the HAD2 and LAD2 lines and significantly suppressed subsequent voluntary alcohol intake in rats of the HAD2 line.
Reduced acoustic startle reactivity during alcohol withdrawal in both HAD2 and LAD2 rats is consistent with our previous findings in the HAD2 but not the LAD2 line and may reflect reduced CNS excitability during withdrawal from forced alcohol exposure. Forced alcohol exposure robustly retarded the expression of a genetic predisposition toward alcohol drinking in rats selectively bred for high alcohol intake.
本研究的目的是确定我们之前在急性给予酒精的未接触过酒精的大鼠中所发现的酒精戒断程度与饮酒遗传倾向之间的反向遗传关联,在慢性酒精暴露后是否也会出现。还研究了强迫性慢性酒精处理对随后自愿饮酒的影响。
来自高饮酒量(HAD2)和低饮酒量(LAD2)品系的雄性大鼠连续20天每天接受两次胃内(IG)酒精输注(3.0 g/kg体重;25% v/v)或等体积的水,两次输注间隔5小时(慢性酒精处理)。在第1、5、10、15和20天,在第二次输注后10、14和18小时评估听觉惊吓反应性。在听觉惊吓测试完成后,所有大鼠接受两次3.0 g酒精/kg体重的IG输注,间隔5小时,并在第二次酒精输注后10、14和18小时评估血液酒精含量。然后所有大鼠在酒精和水之间自由选择24小时,持续8周。
在酒精处理的HAD2和LAD2大鼠中,经过5、10和15天的酒精处理后,在酒精戒断期间对120 dB音调的惊吓幅度受到抑制。强迫性慢性酒精处理在HAD2和LAD2品系中均产生了代谢耐受性,并显著抑制了HAD2品系大鼠随后的自愿酒精摄入量。
HAD2和LAD2大鼠在酒精戒断期间听觉惊吓反应性降低与我们之前在HAD2品系而非LAD2品系中的发现一致,可能反映了在强迫性酒精暴露戒断期间中枢神经系统兴奋性降低。强迫性酒精暴露强烈抑制了为高酒精摄入量而选择性培育的大鼠中饮酒遗传倾向的表达。