Füllgrabe Marc W, Vengeliene Valentina, Spanagel Rainer
Department of Psychopharmacology, University of Heidelberg, Central Institute of Mental Health (CIMH), J5, 68159 Mannheim, Germany.
Pharmacol Biochem Behav. 2007 Feb;86(2):320-6. doi: 10.1016/j.pbb.2006.10.004. Epub 2006 Nov 13.
We have recently observed increased stress responsiveness with regard to alcohol consumption in male rats that consumed alcohol since their adolescent period. Thus, early age at drinking onset can induce enhanced stress-induced alcohol drinking in male rats. However, it is not known whether female rats respond in a similar way. Therefore, we compared the drinking behavior of two female Wistar rat groups--one that acquired alcohol consumption during adolescence (adolescent group) and the other that acquired their drinking during adulthood (adult group) in a model of long-term voluntary alcohol drinking with repeated deprivation and stress phases. Furthermore, we studied the influence of age at drinking onset on the efficacy of acamprosate treatment. Thirty-nine female Wistar rats aged 31 days (adolescents) and 71 days (adults) were given ad libitum access to water, as well as to 5% and 20% ethanol solutions during an observation period of 29 weeks. A deprivation phase of 14 days was introduced following 8 weeks of access to alcohol in order to measure the alcohol deprivation effect (ADE). After 15 and 25 weeks of alcohol access, all animals were subjected for 3 consecutive days of forced swim and electric foot-shock stress, respectively. After 29 weeks of access to alcohol all animals underwent a second deprivation phase and the subsequent ADE was measured either under acamprosate (200 mg/kg) or vehicle treatment. Drinking before the first deprivation phase was not different between animal groups. However, the expression of the first ADE was more pronounced in adult female rats and alcohol intake stayed increased for the remainder of the experiment in the adult group. Both repeated swim stress and foot-shock stress produced a more pronounced increase in ethanol consumption in the adolescent group compared to the adult group. Acamprosate reduced relapse-like drinking in the adult female rat group. However, it had no effect on the ADE in the adolescent group. In conclusion, female rats that initiate alcohol consumption during adolescence might be more susceptible to stress-induced alcohol consumption. Adolescent alcohol drinking might also result in a reduced response to acamprosate.
我们最近观察到，自青春期开始饮酒的雄性大鼠在酒精摄入方面的应激反应性增强。因此，饮酒起始年龄较早可诱导雄性大鼠应激诱导的酒精摄入增加。然而，尚不清楚雌性大鼠是否有类似反应。因此，我们在一个长期自愿饮酒且有反复剥夺和应激阶段的模型中，比较了两组雌性Wistar大鼠的饮酒行为——一组在青春期开始饮酒（青春期组），另一组在成年期开始饮酒（成年组）。此外，我们研究了饮酒起始年龄对阿坎酸治疗效果的影响。39只31日龄（青春期）和71日龄（成年期）的雌性Wistar大鼠在29周的观察期内可随意获取水以及5%和20%的乙醇溶液。在获取酒精8周后引入14天的剥夺期，以测量酒精剥夺效应（ADE）。在获取酒精15周和25周后，所有动物分别连续3天接受强迫游泳和电足部电击应激。在获取酒精29周后，所有动物进入第二个剥夺期，并在阿坎酸（200mg/kg）或赋形剂治疗下测量随后的ADE。在第一个剥夺期之前，两组动物的饮酒情况没有差异。然而，成年雌性大鼠中第一个ADE的表现更明显，并且在成年组中，酒精摄入量在实验剩余时间内持续增加。与成年组相比，青春期组反复的游泳应激和足部电击应激均使乙醇摄入量有更明显的增加。阿坎酸减少了成年雌性大鼠组中类似复发的饮酒行为。然而，它对青春期组的ADE没有影响。总之，青春期开始饮酒的雌性大鼠可能更容易受到应激诱导的酒精摄入影响。青春期饮酒还可能导致对阿坎酸的反应降低。
