Silva Lindsay, Black Rita, Michaelides Michael, Hurd Yasmin L, Dow-Edwards Diana
School of Graduate Studies, SUNY Downstate Medical Center, 450 Clarkson Ave, MSC 41, Brooklyn, 11203, NY, USA.
Icahn School of Medicine at Mount Sinai, Department of Psychiatry and Neuroscience, Hess Center for Science and Medicine Building, 1470 Madison Avenue, New York, NY 11029, USA.
Neurotoxicol Teratol. 2016 Nov-Dec;58:88-100. doi: 10.1016/j.ntt.2016.02.005. Epub 2016 Feb 16.
Adolescents who use marijuana are more likely to exhibit anxiety, depression, and other mood disorders, including psychotic-like symptoms. Additionally, the age at onset of use and the stress history of the individual can affect responses to cannabis. To examine the effect of early life experience on adolescent Δ-9-tetrahydrocannabinol (THC) exposure, we exposed adolescent (postnatal day (P) 29-38) male and female rats, either shipped from a supplier or born in our vivarium, to once daily injections of 3mg/kg THC. Our findings suggest that males are more sensitive to the anxiolytic and antidepressant effects of THC, as measured by the elevated plus maze (EPM) and forced swim test (FST), respectively, than females. Exposure to the FST increased plasma corticosterone levels, regardless of drug treatment or origin and females had higher levels than males overall. Shipping increased THC responses in females (acoustic startle habituation) and in males (latency to immobility in FST). No significant effects of THC or shipping on pre-pulse inhibition were observed. Due to differences in timing of puberty in males and females during the P29-38 period of THC treatment, we also dosed female rats between P21-30 (pre-puberty) and male rats between P39-48 (puberty). Pre-pubertal animals showed reductions in anxiety on the EPM, an effect that was not seen in animals treated during puberty. These results suggest that both sexes are more susceptible to changes in emotional behavior when THC exposure occurs just prior to the onset of puberty. Within the animals dosed from P29-38, THC increased cannabinoid receptor 1 (CB1R) mRNA expression and tended to decrease CP55,940 stimulated [S]GTPγS binding in the central amygdala only of females. Therefore, early stress enhances THC responses in males (in FST) and females (ASR habituation), THC alters CB1R expression and function in females only and prepubescent rats are generally more responsive to THC than pubertal rats. In summary, THC and stress interact with the developing endocannabinoid system in a sex specific manner during the peri-pubertal period.
吸食大麻的青少年更有可能出现焦虑、抑郁和其他情绪障碍，包括类似精神病的症状。此外，开始使用大麻的年龄以及个体的应激史会影响对大麻的反应。为了研究早期生活经历对青少年Δ-9-四氢大麻酚（THC）暴露的影响，我们对从供应商处运来或在我们的动物饲养室出生的青春期（出生后第（P）29 - 38天）雄性和雌性大鼠，每天注射一次3mg/kg的THC。我们的研究结果表明，通过高架十字迷宫（EPM）和强迫游泳试验（FST）分别测量，雄性对THC的抗焦虑和抗抑郁作用比雌性更敏感。无论药物治疗或来源如何，暴露于FST都会增加血浆皮质酮水平，总体上雌性的水平高于雄性。运输增加了雌性（听觉惊吓习惯化）和雄性（FST中不动潜伏期）对THC的反应。未观察到THC或运输对前脉冲抑制有显著影响。由于在THC治疗的P29 - 38期间雄性和雌性青春期时间不同，我们还在P21 - 30（青春期前）给雌性大鼠给药，在P39 - 48（青春期）给雄性大鼠给药。青春期前的动物在EPM上表现出焦虑减轻，而在青春期接受治疗的动物中未观察到这种效果。这些结果表明，当THC暴露发生在青春期开始之前时，两性对情绪行为变化更敏感。在P29 - 38给药的动物中，THC增加了大麻素受体1（CB1R）mRNA表达，并且仅在雌性的中央杏仁核中倾向于降低CP55,940刺激的[S]GTPγS结合。因此，早期应激增强了雄性（在FST中）和雌性（听觉惊吓反应习惯化）对THC的反应，THC仅改变雌性的CB1R表达和功能，并且青春期前的大鼠通常比青春期大鼠对THC更敏感。总之，在青春期前后，THC和应激以性别特异性方式与发育中的内源性大麻素系统相互作用。
