Wake Forest University School of Medicine, Department of Physiology and Pharmacology, Winston-Salem, NC, United States.
J Exp Anal Behav. 2023 May;119(3):488-500. doi: 10.1002/jeab.834. Epub 2023 Feb 14.
The progression of recreational drinking to alcohol use disorder is characterized by loss of control over seeking, which involves continued use of alcohol despite negative consequences. The present study proposes a novel maladaptive alcohol self-administration task in which animals are trained to withhold alcohol drinking in the presence of an auditory cue signaling consequence (conflict phase) but to drink freely when there is no consequence (neutral phase). These phases are performed within trial; successful performance involves waiting for the conflict phase to end and drinking during the neutral phase. We discuss the background and implementation of the task, its relation to existing models, and its relevance to the field of translational alcohol research. Importantly, we also present evidence of its efficacy. Both male and female Long-Evans rats are capable of performing the maladaptive alcohol self-administration task for both sweetened and unsweetened alcohol solutions. Finally, we show that acute injection of a pharmacological stressor (yohimbine) significantly disrupted performance of the task in both sexes and reinforcers. We suggest the maladaptive alcohol self-administration task may prove particularly useful in models of alcohol use disorder or vulnerability to this disorder where its application may reveal maladaptive neural circuit adaptations responsible for motivational perturbations associated with loss of control over alcohol seeking.
消遣性饮酒发展为酒精使用障碍的特征是寻求失控,这涉及到尽管有负面后果仍继续使用酒精。本研究提出了一种新颖的适应性不良的酒精自我给药任务,在该任务中,动物被训练在听觉提示信号后果(冲突阶段)的存在下抑制酒精摄入,但在没有后果(中性阶段)的情况下自由饮酒。这些阶段在试验内进行;成功的表现包括等待冲突阶段结束并在中性阶段饮酒。我们讨论了任务的背景和实施,它与现有模型的关系,以及它与转化酒精研究领域的相关性。重要的是,我们还提供了其功效的证据。雄性和雌性长耳大仓鼠均能够对加糖和无糖酒精溶液执行适应性不良的酒精自我给药任务。最后,我们表明,急性注射药理学应激源(育亨宾)会显著破坏两性动物的任务表现和强化作用。我们认为,适应性不良的酒精自我给药任务可能在酒精使用障碍或对这种障碍的易感性模型中特别有用,因为它的应用可能会揭示导致对酒精寻求失去控制的动机波动的适应性不良的神经回路适应性。