背景:内源性大麻素系统对奖励处理做出了重要贡献,动机,和行为控制。反复暴露于THC或其他大麻素药物可导致内源性大麻素系统和相关神经回路的持续适应。目前尚不清楚此类治疗如何影响处理和追求奖励的方式。
目的:我们研究了在青春期或成年期重复暴露THC(5mg/kg/天,持续14天)是否会导致大鼠灵活编码和使用行动-结果关联进行目标导向决策的能力的长期变化。还评估了对快感喂养和渐进比例反应的影响。
结果:THC暴露对大鼠在奖励贬值后灵活选择动作的能力没有影响。然而,仪器应急退化学习,这包括避免奖励传递不必要的行动,在有成年但青少年THC暴露史的大鼠中增加。在这项研究中,暴露于THC的大鼠也表现出更有力的工具行为,建议动机增强。一项单独的实验发现,虽然暴露于THC对享乐进食行为没有影响,它增加了老鼠以渐进的比例计划为食物工作的意愿,当向成人施用THC时,效果更明显。青少年和成人THC暴露对CB1受体依赖性的渐进比率表现有相反的影响,对利莫那班诱导的行为抑制的敏感性降低和增加,分别。
结论:我们的发现表明,暴露于与翻译相关的THC暴露方案会导致长期持续,调节奖励追求的认知和动机过程中的年龄依赖性变化。
BACKGROUND: The endocannabinoid system makes critical contributions to reward processing, motivation, and behavioral control. Repeated exposure to THC or other cannabinoid drugs can cause persistent adaptions in the endocannabinoid system and associated neural circuitry. It remains unclear how such treatments affect the way rewards are processed and pursued.
OBJECTIVE: We examined if repeated THC exposure (5 mg/kg/day for 14 days) during adolescence or adulthood led to long-term changes in rats\' capacity to flexibly encode and use action-outcome associations for goal-directed decision making. Effects on hedonic feeding and progressive ratio responding were also assessed.
RESULTS: THC exposure had no effect on rats\' ability to flexibly select actions following reward devaluation. However, instrumental contingency degradation learning, which involves avoiding an action that is unnecessary for reward delivery, was augmented in rats with a history of adult but not adolescent THC exposure. THC-exposed rats also displayed more vigorous instrumental behavior in this study, suggesting a motivational enhancement. A separate experiment found that while THC exposure had no effect on hedonic feeding behavior, it increased rats\' willingness to work for food on a progressive ratio schedule, an effect that was more pronounced when THC was administered to adults. Adolescent and adult THC exposure had opposing effects on the CB1 receptor dependence of progressive ratio performance, decreasing and increasing sensitivity to rimonabant-induced behavioral suppression, respectively.
CONCLUSIONS: Our findings reveal that exposure to a translationally relevant THC exposure regimen induces long-lasting, age-dependent alterations in cognitive and motivational processes that regulate the pursuit of rewards.