Graduate Program in Biosciences applied to Health, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.
Undergraduate student in Medicine, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.
Behav Brain Res. 2024 Oct 2;474:115175. doi: 10.1016/j.bbr.2024.115175. Epub 2024 Aug 6.
Stress-related disorders are becoming increasingly common and are often associated with cognitive impairments. Within this context, the endocannabinoid (ECB) system, particularly the type 1 cannabinoid (CB1) receptor, seems to play a decisive role in restoring body homeostasis. There is consistent evidence in the literature that disrupted CB1-mediated neurotransmission can ultimately contribute to stress-related diseases. Therefore, the present study aimed to evaluate the participation of CB1 receptors in the integrity of stress-induced peripheral and behavioral responses. For this purpose, male adult Wistar rats underwent physical restraint (1 h/day, for 7 days), followed by a single administration of rimonabant (CB1 receptor antagonist, 3 mg/Kg, intraperitonial) at the end of stress protocol. Animals were then subjected to evaluation of neuroendocrine responses, behavioral tests and quantification of Iba-1 (microglial) immunoreactivity in the parvocellular subdivisions of the paraventricular nucleus of the hypothalamus (PVN). No effects of restraint stress or rimonabant administration were detected on body mass variation. However, stress significantly increased adrenal relative mass and corticosterone secretion, and reduced thymus relative size. The stress effects on adrenal size and corticosterone plasma levels were absent in rimonabant-treated rats, but the thymus size was further reduced in the restraint-rimonabant group. Restraint stress also induced anhedonia, a depression-like behavior, and reduced object recognition index, indicating memory recovery impairment. Treatment with the CB1 antagonist significantly reversed stress-induced anhedonia and memory deficit. In the PVN, restraint stress reduced the number of Iba-1 positive cells in the medial parvocellular region of vehicle- but not rimonabant-treated animals. Taken together, these results indicate that the acute inhibition of the CB1-mediated endogenous pathway restores stress-induced depression-like behaviors and memory loss, suggesting a role for endocannabinoids in the neuro-immune-endocrine interplay at both peripheral and hypothalamic levels.
应激相关障碍越来越常见，且常与认知障碍相关。在这种情况下，内源性大麻素（ECB）系统，尤其是 1 型大麻素（CB1）受体，似乎在恢复体内平衡方面发挥着决定性作用。文献中有一致的证据表明，CB1 介导的神经传递中断最终可能导致与应激相关的疾病。因此，本研究旨在评估 CB1 受体在应激诱导的外周和行为反应完整性中的参与。为此，雄性成年 Wistar 大鼠接受 1 小时/天的身体束缚（共 7 天），然后在应激方案结束时单次给予利莫那班（CB1 受体拮抗剂，3mg/kg，腹腔内）。然后，对动物进行神经内分泌反应评估、行为测试以及下丘脑室旁核中小细胞区（PVN）中 Iba-1（小胶质细胞）免疫反应性的定量。束缚应激或利莫那班给药对体重变化没有影响。然而，应激显著增加了肾上腺相对质量和皮质酮分泌，并降低了胸腺相对大小。利莫那班处理的大鼠中应激对肾上腺大小和皮质酮血浆水平的影响消失，但束缚-利莫那班组的胸腺大小进一步减小。束缚应激还诱导快感缺失，即抑郁样行为，并降低物体识别指数，表明记忆恢复受损。CB1 拮抗剂的治疗显著逆转了应激诱导的快感缺失和记忆缺陷。在 PVN 中，束缚应激降低了载体处理但未降低利莫那班处理的动物中内侧小细胞区 Iba-1 阳性细胞的数量。总之，这些结果表明，急性抑制 CB1 介导的内源性途径可恢复应激诱导的抑郁样行为和记忆丧失，表明内源性大麻素在周围和下丘脑水平的神经免疫内分泌相互作用中起作用。
