Sleep deprivation alters orexinergic neuronal activity in the lateral hypothalamus (LH), which is the main regulator of sleep-wake, arousal, appetite, and energy regulation processes. Cannabinoid receptor (CBR) expression in this area is involved in modulating the function of orexin neurons. In this study, we investigated the effects of endocannabinoid anandamide (AEA) administration on improving food intake and appetite by modulating the activity of orexin neurons and CB1R expression after chronic sleep deprivation. Adult male Wistar rats (200–250 g) were randomly divided into three groups: control + vehicle (Control), chronic sleep deprivation + vehicle (SD), and chronic sleep deprivation +20 mg/kg AEA (SD + A). For SD induction, the rats were kept in a sleep deprivation device for 18 h (7 a.m. to 1 a.m.) daily for 21 days. Weight gain, food intake, the electrical power of orexin neurons, CB1R mRNA expression in hypothalamus, CB1R protein expression in the LH, TNF-α, IL-6, IL-4 levels and antioxidant activity in hypothalamus were measured after SD induction. Our results showed that AEA administration significantly improved food intake (p < 0.01), Electrical activity of orexin neurons (p < 0.05), CB1R expression in the hypothalamus (p < 0.05), and IL-4 levels (p < 0.05). AEA also reduced mRNA expression of OX1R and OX2R (p < 0.01 and p < 0.05 respectively), also IL-6 and TNF-α (p < 0.01) and MDA level (p < 0.05) in hypothalamic tissue. As a consequence, AEA modulates orexinergic system function and improves food intake by regulating the expression of the CB1 receptor in the LH in sleep deprived rats.

睡眠不足会改变下丘脑外侧部(LH) 的食欲素能神经元活动，而下丘脑是睡眠-觉醒、觉醒、食欲和能量调节过程的主要调节器。该区域的大麻素受体（CBR）表达参与调节食欲素神经元的功能。在这项研究中，我们通过调节长期睡眠剥夺后食欲素神经元的活性和 CB1R 表达，研究了内源性大麻素anandamide (AEA) 给药对改善食物摄入和食欲的影响。成年雄性Wistar大鼠（200-250 g）随机分为三组：对照组+媒介物（Control）、慢性睡眠剥夺+媒介物（SD）和慢性睡眠剥夺+20 mg/kg AEA（SD + A）。为了进行 SD 诱导，将大鼠每天置于睡眠剥夺装置中 18 小时（上午 7 点至凌晨 1 点），持续 21 天。SD诱导后测定体重增加、食物摄入量、食欲素神经元电功率、下丘脑CB1R mRNA表达、LH中CB1R蛋白表达、下丘脑TNF-α、IL-6、IL-4水平和抗氧化活性。我们的结果表明，AEA 给药显着改善食物摄入量 ( p < 0.01)、食欲素神经元电活动 (p < 0.05)、下丘脑 CB1R 表达 (p < 0.05) 和 IL-4 水平 (p < 0.05)。AEA 还降低下丘脑组织中OX1R 和 OX2R 的 mRNA 表达（ 分别为p因此，AEA 通过调节睡眠剥夺大鼠 LH 中 CB1 受体的表达来调节食欲素系统功能并改善食物摄入。