Kimbrough Adam, Kim Sarah, Cole Maury, Brennan Molly, George Olivier
Department of Neuroscience, The Scripps Research Institute, La Jolla, California.
Alcohol Clin Exp Res. 2017 Aug;41(8):1502-1509. doi: 10.1111/acer.13434. Epub 2017 Jul 5.
Alcohol binge drinking in humans is thought to increase the risk for alcohol use disorder (AUD). Unclear is whether drinking patterns (e.g., bingelike or stable drinking) differentially affect the transition to compulsive-like drinking in dependent individuals. We examined whether chronic bingelike drinking facilitates the transition to compulsive-like drinking in rats.
Male Wistar rats were given 5 months of intermittent access to ethanol (EtOH) (IAE) or continuous access to EtOH (CAE) in a 2-bottle choice paradigm. Then, rats were given chronic intermittent EtOH (CIE) vapor exposure. Escalation of EtOH intake and compulsive-like responding for EtOH, using a progressive-ratio schedule of reinforcement and quinine-adulterated EtOH, were measured.
IAE rats escalated EtOH drinking after 2 weeks of 2-bottle choice, whereas CAE rats exhibited stable EtOH drinking for 5 months. After 8 weeks of CIE, both IAE + CIE and CAE + CIE rats escalated their EtOH intake. However, IAE rats escalated their EtOH intake weeks sooner than CAE rats and exhibited greater EtOH intake. No differences in compulsive-like responding were found between IAE + CIE and CAE + CIE rats. However, both IAE + CIE and CAE + CIE rats showed strong compulsive-like responding compared with rats without prior IAE or CAE.
Chronic EtOH drinking at stable or escalated levels for several months is associated with more compulsive-like responding for EtOH in rats that are exposed to CIE compared with rats without a prior history of EtOH drinking. Moreover, IAE facilitated the transition to compulsive-like responding for EtOH after CIE exposure, reflected by the escalation of EtOH intake. These results suggest that IAE may facilitate the transition to AUD. This study indicates that despite a moderate level of EtOH drinking, the IAE animal model is highly relevant to early stages of alcohol abuse and suggests that it may be associated with neuroadaptations that produce a faster transition to alcohol dependence.
人们认为人类酗酒会增加酒精使用障碍（AUD）的风险。目前尚不清楚饮酒模式（如暴饮式或稳定饮酒）是否会对依赖个体向强迫性饮酒的转变产生不同影响。我们研究了长期暴饮式饮酒是否会促进大鼠向强迫性饮酒的转变。
在双瓶选择范式中，给雄性Wistar大鼠5个月间歇性接触乙醇（IAE）或持续接触乙醇（CAE）。然后，让大鼠接受慢性间歇性乙醇（CIE）蒸汽暴露。使用渐进比率强化程序和奎宁掺杂乙醇，测量乙醇摄入量的增加和对乙醇的强迫性反应。
在双瓶选择2周后，IAE组大鼠的乙醇饮用量增加，而CAE组大鼠在5个月内乙醇饮用稳定。CIE 8周后，IAE + CIE组和CAE + CIE组大鼠的乙醇摄入量均增加。然而，IAE组大鼠的乙醇摄入量比CAE组大鼠提前数周增加，且乙醇摄入量更高。IAE + CIE组和CAE + CIE组大鼠在强迫性反应方面没有差异。然而，与没有先前IAE或CAE的大鼠相比，IAE + CIE组和CAE + CIE组大鼠均表现出强烈的强迫性反应。
与没有乙醇饮用史的大鼠相比，在稳定或增加水平下长期饮用乙醇数月的大鼠，在接触CIE后对乙醇表现出更多的强迫性反应。此外，IAE促进了CIE暴露后向对乙醇的强迫性反应的转变，这表现为乙醇摄入量的增加。这些结果表明IAE可能促进向AUD的转变。这项研究表明，尽管乙醇饮用量适中，但IAE动物模型与酒精滥用的早期阶段高度相关，并表明它可能与导致更快向酒精依赖转变的神经适应性有关。
