Background Cannabis exposure during adolescence is associated with emotional and motivational alterations that may entail an enhanced risk of developing psychiatric disorders. In rodent models, exposure to cannabinoids during adolescence leads to increased self-administration of opiates and cocaine, however, the psychological and neural mechanisms and the sex-specificity of this phenomenon are largely unknown. Methods We exposed male and female adolescent rats to Δ9-tetrahydrocannabinol (THC) and studied at adulthood the effects of such treatment on psychological processes related to reward, such as Pavlovian conditioned approach, Pavlovian to instrumental transfer, habit formation and waiting impulsivity. In the light of these data and given the involvement of the nucleus accumbens in the processes examined, we performed an RNASeq transcriptomic study and assessed cocaine addiction-like behavior. Results THC exposure increased goal-tracking (in males and females) and enhanced Pavlovian to instrumental transfer (especially in males) but did not affect habit formation. THC-exposed rats exhibited subtle, state-dependent changes in premature responding in the 2-CSRTT task. RNASeq data showed gene expression alterations in a marked sex-specific manner. While no effects were found on the acquisition of cocaine self-administration or punished drug-seeking, rats exposed to THC self-administered more cocaine under a progressive ratio schedule (males), had a higher rebound upon returning to continuous access to the drug (females) and showed reduced drug-seeking after 30 days of withdrawal (females). Conclusions Adolescent THC affects specific aspects of reward- (and cocaine-) guided behavior and the function of a key brain region mediating these effects, in a remarkable sex-specific manner.

中文翻译：

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青春期期间的 Δ 9-四氢大麻酚会重新编程伏核转录组，以性别依赖性方式影响奖励处理、冲动和可卡因成瘾样行为的特定方面

背景 青春期接触大麻与情绪和动机改变有关，这可能会增加患精神疾病的风险。在啮齿动物模型中，青春期接触大麻素会导致阿片类药物和可卡因的自我施用增加，然而，这种现象的心理和神经机制以及性别特异性在很大程度上尚不清楚。方法我们将雄性和雌性青春期大鼠暴露于Δ9-四氢大麻酚（THC），并在成年后研究这种治疗对与奖励相关的心理过程的影响，例如巴甫洛夫条件方法、巴甫洛夫工具转移、习惯形成和等待冲动。根据这些数据并考虑到伏隔核参与所检查的过程，我们进行了 RNASeq 转录组研究并评估了可卡因成瘾样行为。结果 THC 暴露增加了目标追踪（男性和女性）并增强了巴甫洛夫到工具的转移（尤其是男性），但不影响习惯的形成。暴露于 THC 的大鼠在 2-CSRTT 任务中表现出微妙的、状态依赖性的过早反应变化。RNASeq 数据显示基因表达变化具有明显的性别特异性。虽然没有发现对可卡因自我给药或惩罚性药物寻求的影响，但接触 THC 的大鼠在渐进比例方案下自我给药更多可卡因（雄性），在恢复持续使用药物后有更高的反弹。女性），并且在戒断 30 天后（女性）表现出寻求药物的减少。结论 青少年 THC 以显着的性别特异性方式影响奖励（和可卡因）引导行为的特定方面以及介导这些影响的关键大脑区域的功能。