Department of Psychiatry, University of Michigan, Ann Arbor, USA.
Addiction Center, University of Michigan, Ann Arbor, USA.
Psychopharmacology (Berl). 2020 Sep;237(9):2767-2776. doi: 10.1007/s00213-020-05571-3. Epub 2020 Jun 3.
Pavlovian conditioned approach paradigms are used to characterize the nature of motivational behaviors in response to stimuli as either directed toward the cue (i.e., sign-tracking) or the site of reward delivery (i.e., goal-tracking). Recent evidence has shown that activity of the endocannabinoid system increases dopaminergic activity in the mesocorticolimbic system, and other studies have shown that sign-tracking behaviors are dependent on dopamine.
Therefore, we hypothesized that administration of a cannabinoid agonist would increase sign-tracking and decrease goal-tracking behaviors.
Forty-seven adult male Sprague-Dawley rats were given a low, medium, or high dose of the cannabinoid agonist CP-55,940 (N = 12 per group) or saline (N = 11) before Pavlovian conditioned approach training. A separate group of rats (N = 32) were sacrificed after PCA training for measurement of cannabinoid receptor type 1 (CB1) and fatty acid amide hydrolase (FAAH) using in situ hybridization.
Contrary to our initial hypothesis, CP-55,940 dose-dependently decreased sign-tracking and increased goal-tracking behavior. CB1 expression was higher in sign-trackers compared with that in goal-trackers in the prelimbic cortex, but there were no significant differences in CB1 or FAAH expression in the infralimbic cortex, dorsal or ventral CA1, dorsal or ventral CA3, dorsal or ventral dentate gyrus, or amygdala.
These results demonstrate that cannabinoid signaling can specifically influence behavioral biases toward sign- or goal-tracking. Pre-existing differences in CB1 expression patterns, particularly in the prelimbic cortex, could contribute to individual differences in the tendency to attribute incentive salience to reward cues.
巴甫洛夫条件趋近范式被用于描述对刺激的动机行为的本质,这些行为要么是指向线索(即信号追踪),要么是指向奖励传递的地点(即目标追踪)。最近的证据表明,内源性大麻素系统的活动增加了中脑边缘多巴胺系统的多巴胺活性,而其他研究表明,信号追踪行为依赖于多巴胺。
因此,我们假设给予大麻素激动剂会增加信号追踪行为并减少目标追踪行为。
47 只成年雄性 Sprague-Dawley 大鼠在接受低、中、高剂量的大麻素激动剂 CP-55,940(每组 12 只)或生理盐水(每组 11 只)之前接受了巴甫洛夫条件趋近训练。另一组大鼠(n = 32)在 PCA 训练后被处死,用于通过原位杂交测量大麻素受体 1(CB1)和脂肪酸酰胺水解酶(FAAH)。
与我们最初的假设相反,CP-55,940 剂量依赖性地降低了信号追踪行为并增加了目标追踪行为。在额前皮质中,与目标追踪者相比,信号追踪者的 CB1 表达更高,但在边缘下皮质、背侧或腹侧 CA1、背侧或腹侧 CA3、背侧或腹侧齿状回或杏仁核中,CB1 或 FAAH 表达没有显著差异。
这些结果表明,大麻素信号可以特异性地影响对信号或目标追踪的行为偏向。CB1 表达模式的预先存在差异,特别是在额前皮质中,可能导致对奖励线索归因于激励显著性的个体差异。