与压力相关的疾病变得越来越普遍,并且通常与认知障碍有关。在此背景下,内源性大麻素(ECB)系统,特别是1型大麻素(CB1)受体,似乎在恢复身体稳态中起着决定性的作用。文献中有一致的证据表明,CB1介导的神经传递被破坏最终会导致应激相关疾病。因此,本研究旨在评估CB1受体参与应激诱导的外周和行为反应的完整性。为此,雄性成年Wistar大鼠进行身体约束(1h/day,7天),随后单次施用利莫那班(CB1受体拮抗剂,3mg/Kg,在压力方案结束时)。然后对动物进行神经内分泌反应的评估,下丘脑室旁核(PVN)的小细胞细分中Iba-1(小胶质细胞)免疫反应性的行为测试和定量。未检测到束缚应激或利莫那班给药对体重变化的影响。然而,应激显著增加肾上腺相对质量和皮质酮分泌,减少胸腺的相对大小。利莫那班治疗的大鼠不存在对肾上腺大小和皮质酮血浆水平的应激反应,但克制利莫那班组的胸腺大小进一步减小。束缚压力也会导致快感缺失,类似抑郁的行为,并降低了物体识别指数,表明记忆恢复受损。用CB1拮抗剂治疗可显着逆转应激诱导的快感缺失和记忆缺陷。在PVN中,束缚应激减少了经利莫那班治疗的动物的内侧细小细胞区域中Iba-1阳性细胞的数量,但没有减少。一起来看,这些结果表明,对CB1介导的内源性途径的急性抑制可以恢复应激诱导的抑郁样行为和记忆丧失,提示内源性大麻素在外周和下丘脑水平的神经-免疫-内分泌相互作用中的作用。
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.