Neuroscience Department, Oberlin College, 173 Lorain St., Oberlin, OH, USA.
Department of Biomedical Science, Grand Valley State University, Allendale, MI, USA.
Behav Brain Res. 2022 Sep 26;434:114023. doi: 10.1016/j.bbr.2022.114023. Epub 2022 Jul 25.
Habits are inflexible behaviors that persist despite changes in outcome value. While habits allow for efficient responding, neuropsychiatric diseases such as drug addiction and obsessive-compulsive disorder are characterized by overreliance on habits. Recently, the commercially popular drug cannabidiol (CBD) has emerged as a potential treatment for addictive behaviors, though it is not entirely clear how it exerts this therapeutic effect. As brain endocannabinoids play a key role in habit formation, we sought to determine how CBD modifies goal-directed behaviors and habit formation. To explore this, mice were administered CBD (20 mg/kg i.p.) or vehicle as a control and trained on random interval (RI30/60) or random ratio (RR10/20) schedules designed to elicit habitual or goal-directed lever pressing, respectively. Mice were tested for habitual responding using probe trials following reinforcer-specific devaluation as well as omission trials, where mice had to withhold responding to earn rewards. We found that while CBD had little effect on operant behaviors or reward devaluation, CBD inhibited goal-directed behavior in a sex-specific and context dependent manner during the omission task. Beyond drug treatment, we found an effect of sex throughout training, reward devaluation, and omission. This work provides evidence that CBD has no effect on habit formation in a reward devaluation paradigm. However, the omission results suggest that CBD may slow learning of novel action outcome contingencies or decrease goal-directed behavior. This work calls for further examination of sex-dependent outcomes of CBD treatment and highlights the importance of investigating sex effects in habit-related experiments.
习惯是一种尽管结果价值发生变化仍持续存在的不灵活行为。虽然习惯可以提高反应效率，但药物成瘾和强迫症等神经精神疾病的特点是过度依赖习惯。最近，商业上流行的药物大麻二酚 (CBD) 已成为治疗成瘾行为的潜在药物，尽管其发挥这种治疗效果的机制尚不完全清楚。由于大脑内源性大麻素在习惯形成中起着关键作用，我们试图确定 CBD 如何改变目标导向行为和习惯形成。为此，我们给小鼠腹腔注射 CBD（20mg/kg）或对照溶剂，并分别在随机间隔（RI30/60）或随机比率（RR10/20）程序上进行训练，以分别引出习惯或目标导向的压杆反应。在强化物特异性贬值以及省略试验后，我们用探针试验测试小鼠的习惯反应，在省略试验中，小鼠必须抑制反应才能获得奖励。我们发现，虽然 CBD 对操作性行为或奖励贬值几乎没有影响，但 CBD 以性别特异性和上下文依赖的方式抑制了省略任务中的目标导向行为。除了药物治疗，我们还在整个训练、奖励贬值和省略过程中发现了性别的影响。这项工作提供了证据，表明 CBD 在奖励贬值范式中对习惯形成没有影响。然而，省略结果表明，CBD 可能会减缓对新的行为结果关联的学习，或降低目标导向行为。这项工作呼吁进一步研究 CBD 治疗的性别依赖性结果，并强调了在与习惯相关的实验中研究性别效应的重要性。
