Silva Lindsay, Harte-Hargrove Lauren, Izenwasser Sari, Frank Ashley, Wade Dean, Dow-Edwards Diana
Department of Physiology and Pharmacology, SUNY Downstate Medical Center, 450Clarkson Ave, Mail Stop 29, Brooklyn, NY 11203, USA.
Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, 1600 NW 10th Avenue, Room 4113A (D-80), Miami, FL 33136 USA.
Neurosci Lett. 2015 Aug 18;602:89-94. doi: 10.1016/j.neulet.2015.06.033. Epub 2015 Jun 26.
Marijuana use by adolescents has been on the rise since the early 1990s. With recent legalization and decriminalization acts passed, cannabinoid exposure in adolescents will undoubtedly increase. Human studies are limited in their ability to examine underlying changes in brain biochemistry making rodent models valuable. Studies in adult and adolescent animals show region and sex specific downregulation of the cannabinoid 1 (CB1) receptor following chronic cannabinoid treatment. However, although sex-dependent changes in behavior have been observed during the drug abstinence period following adolescent cannabinoid exposure, little is known about CB1 receptor expression during this critical time. In order to characterize CB1 receptor expression following chronic adolescent Δ-9-tetrahydrocannabinol (THC) exposure, we used [(3)H] CP55,940 binding to assess CB1 receptor expression in the dentate gyrus and areas CA1, CA2, and CA3 of the hippocampus in both male and female adolescent rats at both 24h and 2 weeks post chronic THC treatment. Consistent with other reported findings, we found downregulation of the CB1 receptor in the hippocampal formation at 24h post treatment. While this downregulation persisted in both sexes following two weeks of abstinence in the CA2 region, in females, this downregulation also persisted in areas CA1 and CA3. Expression in the dentate gyrus returned to the normal range by two weeks. These data suggest that selective regions of the hippocampus show persistent reductions in CB1 receptor expression and that these reductions are more widespread in female compared to male adolescents.
自20世纪90年代初以来,青少年使用大麻的情况一直在上升。随着近期大麻合法化和非刑罪化法案的通过,青少年接触大麻素的情况无疑会增加。人体研究在检查大脑生物化学潜在变化方面能力有限,这使得啮齿动物模型变得很有价值。对成年和青少年动物的研究表明,长期使用大麻素治疗后,大麻素1(CB1)受体在区域和性别上存在特异性下调。然而,尽管在青少年接触大麻素后的药物戒断期观察到了行为上的性别依赖性变化,但在这个关键时期CB1受体的表达情况却知之甚少。为了描述青少年长期接触Δ-9-四氢大麻酚(THC)后CB1受体的表达情况,我们在长期THC治疗后的24小时和2周,使用[(3)H] CP55,940结合法评估雄性和雌性青少年大鼠海马齿状回以及海马体CA1、CA2和CA3区域的CB1受体表达。与其他报道的结果一致,我们发现在治疗后24小时海马结构中的CB1受体下调。虽然在CA2区域禁欲两周后,这种下调在两性中都持续存在,但在雌性中,CA1和CA3区域的这种下调也持续存在。齿状回的表达在两周后恢复到正常范围。这些数据表明,海马体的特定区域显示CB1受体表达持续减少,并且与雄性青少年相比,这些减少在雌性中更为普遍。