From the, Department of Psychology, (RR, CMG), University of California San Diego, La Jolla, California.
The Neurosciences Graduate Program, (CC, CMG), University of California San Diego, La Jolla, California.
Alcohol Clin Exp Res. 2020 Apr;44(4):880-891. doi: 10.1111/acer.14302. Epub 2020 Feb 25.
A significant component of ethanol (EtOH) dependence is the disruption to decision-making processes. Prior work has shown EtOH dependence biases habitual seeking of EtOH and disrupts neural mechanisms supporting decision-making. This has contributed to the hypothesis that habitual EtOH seeking in EtOH dependence may promote excessive habitual or compulsive EtOH consumption. However, decision-making and behavioral processes underlying seeking and consummatory behaviors differ. Here, we examine the microstructure of EtOH consummatory behavior in the context of habitual EtOH seeking.
Following home cage pre-exposure to EtOH, C57Bl/6J mice underwent 4 rounds of chronic intermittent EtOH (CIE) or air exposure. Following acute withdrawal, mice began training for operant self-administration of 15% EtOH. Training consisted of 16-hour sessions in which mice were trained in a random ratio (RR) schedule of reinforcement for 30-second access to the EtOH sipper. To test for CIE-induced changes in action control, we used sensory-specific satiation and assessed the effect of outcome devaluation on EtOH seeking. Importantly, the use of a lickometer during operant training allowed us to measure the microstructure of lick behavior.
Prior induction of EtOH dependence led to increased EtOH seeking, consumption, and an insensitivity to outcome devaluation, the latter indicative of habitual EtOH seeking. We also found altered consummatory lick patterns in CIE-exposed mice compared to Air controls. While CIE mice had significantly more licks in a burst and a longer burst duration, there were no differences in the total number of bursts compared to Air controls. Furthermore, these EtOH consummatory behaviors correlated with blood EtOH concentrations (BECs), while EtOH-seeking responses did not.
Our results confirm that EtOH dependence can produce habitual EtOH seeking and suggests the increased EtOH consummatory behaviors following EtOH dependence are separable from decision-making processes controlling EtOH seeking.
乙醇(EtOH)依赖的一个重要组成部分是决策过程的中断。先前的工作表明,EtOH 依赖会使习惯性寻求 EtOH 的行为产生偏差,并破坏支持决策的神经机制。这促使人们提出假设,即 EtOH 依赖中的习惯性 EtOH 寻求可能会促进过度习惯性或强迫性的 EtOH 消费。然而,寻求和消费行为的决策和行为过程是不同的。在这里,我们在习惯性 EtOH 寻求的背景下研究 EtOH 消费行为的微观结构。
在经过家笼预暴露于 EtOH 后,C57Bl/6J 小鼠接受 4 轮慢性间歇性 EtOH(CIE)或空气暴露。在急性戒断后,小鼠开始接受 15%EtOH 的操作性自我给药训练。训练包括 16 小时的训练,在此期间,小鼠在随机比率(RR)强化方案中接受训练,以获得 30 秒的 EtOH 吸管访问。为了测试 CIE 诱导的动作控制变化,我们使用感觉特异性饱食并评估结果贬值对 EtOH 寻求的影响。重要的是,在操作性训练期间使用舔舐计可以测量舔舐行为的微观结构。
先前诱导的 EtOH 依赖导致 EtOH 寻求、消耗增加,并且对结果贬值不敏感,后者表明存在习惯性 EtOH 寻求。与空气对照相比,我们还发现 CIE 暴露的小鼠的消费性舔舐模式发生了改变。虽然 CIE 小鼠的爆发次数和爆发持续时间明显更长,但与空气对照相比,爆发总数没有差异。此外,这些 EtOH 消费行为与血液 EtOH 浓度(BEC)相关,而 EtOH 寻求反应则不相关。
我们的结果证实,EtOH 依赖可以产生习惯性 EtOH 寻求,并表明 EtOH 依赖后增加的 EtOH 消费行为与控制 EtOH 寻求的决策过程是可分离的。