Cannabis vapor self-administration elicits sex- and dose-specific alterations in stress reactivity in rats.

Cannabis vapor self-administration elicits sex- and dose-specific alterations in stress reactivity in rats.
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大麻蒸气自我给药会引起大鼠应激反应性的性别和剂量特异性改变。

DOI:
10.1016/j.ynstr.2020.100260
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发表时间:
2020-11
影响因子:
5
通讯作者:
McLaughlin RJ
McLaughlin RJ
中科院分区:
医学2区
文献类型:
--
作者:
Glodosky NC;Cuttler C;Freels TG;Wright HR;Rojas MJ;Baglot SL;Hill MN;McLaughlin RJ

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大麻使用者经常报告说,他们使用大麻的主要原因是缓解压力。最近的研究表明,人类大麻使用者表现出迟钝的应激反应;然而,目前尚不清楚这是长期使用大麻的原因还是后果。确定慢性大麻蒸汽自我服用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,或者蒸汽暴露前的应激反应性是否预测大麻蒸汽自我服用率。在蒸汽自我给药前,雄性和雌性大鼠进行30分钟的急性约束应激,评估应激反应性。然后训练大鼠每天以四种提取物浓度(0、75、150或300 mg/ml)中的一种自我施用含有69.9% Δ9-tetrahydrocannabinol (THC)的大麻提取物蒸汽,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,而另一半则作为无压力对照组。在应激前和应激后立即测量血浆CORT浓度。雌性大鼠比雄性大鼠产生更多的蒸汽。蒸汽前应激反应性不是男女自我给药率的预测因子。无论治疗条件如何,自我雾化后的基础CORT浓度相对于雾化前的评估有所增加。重要的是,大麻自我给药剂量依赖性地降低了雌性大鼠的应激反应,而不是雄性大鼠。这些数据表明,长期使用大麻可以显著抑制雌性大鼠的应激反应,并进一步支持大麻蒸汽自我给药模型在两性大鼠中的应用。
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. 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. 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. 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. 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.
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