Department of Pharmacology, Addiction Science and Toxicology, University of Tennessee Health Science Center, Memphis, TN, USA.
Psychology Department, American University, Washington, DC, USA.
Neuropharmacology. 2023 Sep 1;235:109564. doi: 10.1016/j.neuropharm.2023.109564. Epub 2023 May 5.
The study of Alcohol Use Disorders (AUD) in preclinical models is hampered by difficulty in training rodents to voluntarily consume high levels of alcohol. The intermittency of alcohol access/exposure is well known to modulate alcohol consumption (e.g., alcohol deprivation effect, intermittent-access two-bottle-choice) and recently, intermittent access operant self-administration procedures have been used to produce more intense and binge-like self-administration of intravenous psychostimulant and opioid drugs. In the present study, we sought to systematically manipulate the intermittency of operant self-administered alcohol access to determine the feasibility of promoting more intensified, binge-like alcohol consumption. To this end, 24 male and 23 female NIH Heterogeneous Stock rats were trained to self-administer 10% w/v ethanol, before being split into three different-access groups. Short Access (ShA) rats continued receiving 30-min training sessions, Long Access (LgA) rats received 16-h sessions, and Intermittent Access (IntA) rats received 16-h sessions, wherein the hourly alcohol-access periods were shortened over sessions, down to 2 min. IntA rats demonstrated an increasingly binge-like pattern of alcohol drinking in response to restriction of alcohol access, while ShA and LgA rats maintained stable intake. All groups were tested on orthogonal measures of alcohol-seeking and quinine-punished alcohol drinking. The IntA rats displayed the most punishment-resistant drinking. In a separate experiment, we replicated our main finding, that intermittent access promotes a more binge-like pattern of alcohol self-administration using 8 male and 8 female Wistar rats. In conclusion, intermittent access to self-administered alcohol promotes more intensified self-administration. This approach may be useful in developing preclinical models of binge-like alcohol consumption in AUD.
在临床前模型中研究酒精使用障碍(AUD),由于难以训练啮齿动物自愿消耗高水平的酒精,因此受到阻碍。间歇性获得/暴露酒精会调节酒精消耗(例如,酒精剥夺效应,间歇性双瓶选择),最近,间歇性获得操作性自我给药程序已被用于产生更强烈和 binge 样的静脉内精神兴奋剂和阿片类药物的自我给药。在本研究中,我们试图系统地操纵操作性自我给药中酒精获得的间歇性,以确定促进更强化、 binge 样酒精消耗的可行性。为此,24 只雄性和 23 只雌性 NIH 异质品系大鼠接受训练以自我给予 10%w/v 乙醇,然后分为三组不同的访问组。短访问(ShA)大鼠继续接受 30 分钟的训练课程,长访问(LgA)大鼠接受 16 小时的课程,而间歇性访问(IntA)大鼠接受 16 小时的课程,其中每小时的酒精访问时间随着课程的进行而缩短,降至 2 分钟。IntA 大鼠在限制酒精摄入时表现出越来越 binge 样的酒精饮用模式,而 ShA 和 LgA 大鼠保持稳定的摄入。所有组都接受了酒精寻求和奎宁惩罚性酒精饮用的正交测量。IntA 大鼠显示出最具抵抗性的饮酒行为。在一项单独的实验中,我们使用 8 只雄性和 8 只雌性 Wistar 大鼠复制了我们的主要发现,即间歇性获得促进了更 binge 样的酒精自我给药模式。总之,间歇性获得自我给予的酒精会促进更强化的自我给药。这种方法可能有助于开发 AUD 中 binge 样酒精消耗的临床前模型。