Department of Psychiatry, Alcohol Research Center, University of Connecticut Health Center, Farmington, CT 06030-2103, USA.
Alcohol Alcohol. 2013 Jan-Feb;48(1):28-38. doi: 10.1093/alcalc/ags105. Epub 2012 Sep 20.
We tested whether an exposure to alcohol in late adolescence, an age of rapid increase in neuroactive steroid precursors, would increase voluntary alcohol consumption in adult rats and whether this effect would be modulated by finasteride, an inhibitor of neuroactive steroid synthesis.
In Experiment 1, we exposed male Wistar rats to 8% alcohol during the dark cycle for 1 week during late adolescence [postnatal days (PNDs) 51-58], and then measured voluntary alcohol consumption 1 month later in adulthood (PNDs 91-104). In Experiment 2, finasteride was administered during the forced alcohol exposure in late adolescence and, in Experiment 3, during voluntary alcohol consumption in adulthood. Plasma was collected at the end of each finasteride treatment to confirm the reduction of plasma neuroactive steroid levels.
We found that a daily 12-h exposure to alcohol for 7 days in late adolescence significantly increased voluntary alcohol consumption (4-fold) a month later during adulthood. Finasteride administration in late adolescence increased group alcohol intake in late adolescence but did not block the effect of adolescent alcohol exposure on increasing alcohol preference in adulthood. There was no effect of finasteride treatment in adulthood on alcohol preference.
A daily 12-h exposure to alcohol for 7 days in late adolescence was sufficient to induce chronically increased alcohol preference in adulthood, indicating that this age may be sensitive to the effects of alcohol.
我们测试了在青春期后期（即神经活性类固醇前体快速增加的年龄）暴露于酒精是否会增加成年大鼠的自愿饮酒量，以及这种效应是否会被神经活性类固醇合成抑制剂非那雄胺所调节。
在实验 1 中，我们让雄性 Wistar 大鼠在青春期后期（PND51-58）的黑暗周期中每天暴露于 8%的酒精中 1 周，然后在成年后（PND91-104）测量自愿饮酒量。在实验 2 中，在青春期后期的强制饮酒暴露期间给予非那雄胺，在实验 3 中，在成年期的自愿饮酒期间给予非那雄胺。在每个非那雄胺治疗结束时收集血浆，以确认血浆神经活性类固醇水平的降低。
我们发现，青春期后期每天 12 小时暴露于酒精 7 天，会显著增加一个月后成年期的自愿饮酒量（增加 4 倍）。青春期后期给予非那雄胺会增加青春期后期的组间饮酒量，但不能阻止青春期酒精暴露对成年期增加酒精偏好的影响。成年期给予非那雄胺治疗对酒精偏好没有影响。
青春期后期每天 12 小时暴露于酒精 7 天足以诱导成年期慢性增加的酒精偏好，表明这个年龄段可能对酒精的影响敏感。
