Rationale

Cannabis users frequently report stress relief as their primary reason for use. Recent studies indicate that human cannabis users exhibit blunted stress reactivity; however, it is unknown whether this is a cause or a consequence of chronic cannabis use.

Objectives

To determine whether chronic cannabis vapor self-administration elicits sex- and/or dose-dependent alterations in stress reactivity and basal corticosterone (CORT) concentrations, or whether pre-vapor exposure stress reactivity predicts rates of cannabis vapor self-administration.

Methods

Male and female rats were subjected to 30 min acute restraint stress to assess stress reactivity prior to vapor self-administration. Rats were then trained to self-administer cannabis extract vapor containing 69.9% Δ⁹-tetrahydrocannabinol (THC) at one of four extract concentrations (0, 75, 150, or 300 mg/ml) daily for 30 days. Half of the rats were then subjected to a second restraint stress challenge 24 h after the final self-administration session, while the other half served as no-stress controls. Plasma CORT concentrations were measured prior to stress and immediately post-stress offset.

Results

Female rats earned significantly more vapor deliveries than male rats. Pre-vapor stress reactivity was not a predictor of self-administration rates in either sex. Basal CORT concentrations were increased following vapor self-administration relative to pre-vapor assessment, irrespective of treatment condition. Importantly, cannabis self-administration dose-dependently reduced stress reactivity in female, but not male, rats.

Conclusions

These data indicate that chronic cannabis use can significantly dampen stress reactivity in female rats and further support the use of the cannabis vapor self-administration model in rats of both sexes.

中文翻译：

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大麻蒸气自我给药引起大鼠应激反应的性别和剂量特异性改变

基本原理

大麻使用者经常报告缓解压力是他们使用大麻的主要原因。最近的研究表明，人类大麻使用者表现出迟钝的压力反应；然而，尚不清楚这是长期使用大麻的原因还是结果。

目标

确定慢性大麻蒸气自我给药是否会引起应激反应性和基础皮质酮 (CORT) 浓度的性别和/或剂量依赖性改变，或者蒸汽暴露前应激反应性是否可以预测大麻蒸气自我给药的速率。

方法

雄性和雌性大鼠在蒸汽自我给药前受到 30 分钟的急性约束压力，以评估压力反应性。然后训练大鼠以四种提取物浓度（0、75、150 或 300 毫克/毫升）之一每天自我施用含有 69.9% Δ ^{9 -四氢大麻酚 (THC) 的大麻提取物蒸气，持续 30 天。}一半的大鼠在最后一次自我给药后 24 小时接受第二次约束压力挑战，而另一半作为无压力对照组。血浆 CORT 浓度在应激前和应激后立即测量。

结果

雌性大鼠比雄性大鼠获得更多的蒸汽输送。蒸汽前应激反应不是任何性别自我给药率的预测指标。与蒸汽前评估相比，蒸汽自我给药后基础 CORT 浓度增加，与治疗条件无关。重要的是，大麻自我给药剂量依赖性地降低了雌性而非雄性大鼠的应激反应。

结论

这些数据表明，长期使用大麻可以显着抑制雌性大鼠的应激反应，并进一步支持在两性大鼠中使用大麻蒸气自我给药模型。