Physiology Research Center, Institute of Neuropharmacology, and Department of Physiology and Pharmacology, Medical School, Kerman University of Medical Sciences, Kerman, Iran.
Department of Physiology, Zahedan University of Medical Sciences, Zahedan, Iran.
Life Sci. 2021 Sep 1;280:119723. doi: 10.1016/j.lfs.2021.119723. Epub 2021 Jun 16.
It has been shown that 17β-estradiol (E2) hormone is an essential biological factor for increasing the sensitivity of women to drug abuse. Recent studies have shown a potential overlap between the molecular pathways of cannabinoids and ovarian hormones. The current study evaluated the interference between the marijuana and E2 effect on spatial learning and memory and the role of the G protein-coupled estrogen receptor (GPR30) in young female rats. The animals were separated into two main groups: intact-ovary and ovariectomized (OVX) rats. The latter group received intraperitoneal injections of E2, G-1 (GPR30 agonist), G-15 (GPR30 antagonist), marijuana, and different combinations of these substances for 28 days. Spatial learning and memory were evaluated by the Morris water maze (MWM) test. We also assessed the BDNF (brain-derived neurotrophic factor) concentration and the hippocampal level of GPR30. The results showed a significant reduction of spatial learning and memory in OVX rats compared to intact-ovary rats, which were restored by E2 replacement. Moreover, treatment with G-1 mimicked E2 effects on spatial learning and memory. Marijuana impaired spatial learning and memory in intact-ovary rats, while improved in OVX rats. We also found that treatment with M + E2 induced significant impairment in spatial learning and memory; however, treatment with M + G1 and M + G15 + E2 showed no significant difference. No significant differences in BDNF expression were observed in experimental groups. These results suggest that marijuana and E2 interact in their effect on spatial learning and memory in young female rats, but GPR30 seems to play no role in this interaction.
已证实,17β-雌二醇(E2)激素是提高女性对药物滥用敏感性的重要生物因素。最近的研究表明,大麻素和卵巢激素的分子途径之间存在潜在的重叠。本研究评估了大麻与 E2 对空间学习和记忆的影响以及 G 蛋白偶联雌激素受体(GPR30)在年轻雌性大鼠中的作用。将动物分为两组:完整卵巢和卵巢切除(OVX)大鼠。后者组接受 E2、G-1(GPR30 激动剂)、G-15(GPR30 拮抗剂)、大麻和这些物质的不同组合的腹腔内注射 28 天。空间学习和记忆通过 Morris 水迷宫(MWM)测试进行评估。我们还评估了 BDNF(脑源性神经营养因子)浓度和海马 GPR30 水平。结果表明,与完整卵巢大鼠相比,OVX 大鼠的空间学习和记忆明显降低,E2 替代可恢复其功能。此外,G-1 的治疗模拟了 E2 对空间学习和记忆的作用。大麻在完整卵巢大鼠中损害空间学习和记忆,而在 OVX 大鼠中改善。我们还发现,M+E2 治疗导致空间学习和记忆显著受损;然而,M+G1 和 M+G15+E2 治疗没有显著差异。实验组中 BDNF 表达无显著差异。这些结果表明,大麻和 E2 在年轻雌性大鼠的空间学习和记忆中相互作用,但 GPR30 似乎在这种相互作用中不起作用。