Marusich Julie A, Lefever Timothy W, Antonazzo Kateland R, Craft Rebecca M, Wiley Jenny L
RTI International, Research Triangle Park, NC 27709-2194, USA.
Department of Psychology, Washington State University, Pullman, WA 99164-4820, USA.
Drug Alcohol Depend. 2014 Apr 1;137:20-8. doi: 10.1016/j.drugalcdep.2014.01.019. Epub 2014 Feb 12.
Chronic recreational marijuana users often report withdrawal symptoms when trying to quit, with some reports suggesting withdrawal may be more pronounced in women. In animal models, female rodents show enhanced sensitivity to acute Δ(9)-tetrahydrocannabinol (THC) administration, but chronic administration has been studied little.
Sex differences in THC dependence in rats were examined. Adult male and female Sprague-Dawley rats were administered 30 mg/kg THC or vehicle twice daily for 6.5 days. On day 7, rats were challenged with vehicle or rimonabant, counterbalanced across dosing groups, and were assessed for withdrawal-related behaviors.
During chronic THC dosing, disruption of estrous cycling and weight loss (both sexes) were observed. Whereas overt signs of withdrawal were minimal in THC-treated rats challenged with vehicle, rimonabant precipitated a pronounced withdrawal syndrome in THC-dependent rats that was characterized by changes in a number of domains, including somatic (paw tremors, head twitches, and retropulsion), early-stage cognition (lack of locomotor habituation, disrupted prepulse inhibition), and affective (increased startle reactivity). With the exception of increased retropulsion in female rats, sex differences were not noted. In vehicle-treated rats, rimonabant induced puritis.
This study represents the first examination of THC dependence in adult rats of both sexes, extends previous findings to females, and revealed some sex differences. The results suggest that the changes that occur during precipitated withdrawal from THC extend beyond somatic signs to more nuanced disruptions of cognitive and affective functioning. The breadth of withdrawal signs observed in rodents mirrors those that have been observed in humans.
长期吸食大麻的娱乐性使用者在试图戒断时常常报告有戒断症状，一些报告表明女性的戒断症状可能更明显。在动物模型中，雌性啮齿动物对急性Δ⁹-四氢大麻酚（THC）给药表现出更高的敏感性，但对慢性给药的研究较少。
研究大鼠中THC依赖性的性别差异。成年雄性和雌性Sprague-Dawley大鼠每天两次给予30mg/kg THC或赋形剂，持续6.5天。在第7天，大鼠接受赋形剂或利莫那班激发试验，各给药组相互平衡，评估其戒断相关行为。
在慢性THC给药期间，观察到动情周期紊乱和体重减轻（两性均有）。在用赋形剂激发的THC处理大鼠中，戒断的明显体征极少，而利莫那班在THC依赖性大鼠中引发了明显的戒断综合征，其特征是在多个方面发生变化，包括躯体方面（爪震颤、头部抽搐和后推）、早期认知方面（运动习惯缺乏、前脉冲抑制破坏）和情感方面（惊吓反应性增加）。除雌性大鼠后推增加外，未观察到性别差异。在接受赋形剂处理的大鼠中，利莫那班诱发了瘙痒。
本研究首次对成年雌雄大鼠的THC依赖性进行了研究，将先前的研究结果扩展到雌性，并揭示了一些性别差异。结果表明，从THC突然戒断期间发生的变化不仅限于躯体体征，还包括对认知和情感功能更细微的破坏。在啮齿动物中观察到的戒断体征范围与在人类中观察到的相似。
