Effects of orexin-A on firing activity of gastric distension-sensitive neurons in the basomedial amygdala and food intake in diet-induced obese rats / 中华行为医学与脑科学杂志

ABSTRACT

Objective To investigate the effects of orexin-A on firing activity of gastric distensionsensitive (GD) neurons in the basomedial amygdala (BMA) and food intake in diet-indaced obese rats.Methods Healthy male Wistar rats were selected,and the diet-induced obesity (DIO) rat model and dietinduced resistant (DR) rat model were established by high-fat diet.The effects of orexin-A and an opioid receptor antagonist naloxone on BMA GD neurons were observed by recording the extracellular potentials of single neurons.The effects of orexin-A and naloxone on the food intake of different rats were observed by using BMA catheterization.The mRNA expression and protein expression of orexin-1 receptor (OX-1R) and μ opioid receptor were detected by real-time PCR and Elisa,respectively.Results After microinjection of orexinA into the BMA,the firing frequency of GD-sensitive neurons in the normal rats was significantly increased (GD-E(78.3±6.9)％,GD-Ⅰ(55.5±4.7) ％,P＜0.01),and this effect was completely blocked by OX-1R receptor antagonist SB334867,and naloxone partially blocked the discharge-promoting effect of orexin-A;Compared with the normal rats,the firing frequency of GD-sensitive neurons in the DIO (GD-E(91.6±7.1) ％,GD-Ⅰ(67.9±8.1) ％) and DR(GD-E(87.9±6.8) ％,GD-Ⅰ(69.2±5.8) ％) rats was significantly increased after BMA injection of orexin-A (P＜0.05).After administration of orexin-A into the BMA,food intake of the normal rats,DIO rats and DR rats ((2.38±0.34) g,(3.75 ±0.32) g,(4.01 ±0.38) g,respectively) was significantly increased (P＜0.01),and the food intake of DR and DIO rats were significantly higher than that of normal rats (P＜0.05).After BMA was injected with naloxone,the food intake of rats was inhibited,and the food intake of the DIO rats was significantly lower than that of the DR rats (P＜0.05),food intake of the DR rats was significantly lower than that of the normal rats (P＜0.05).The results of real-time PCR showed that the mRNA levels of OX-1R in DIO and DR rats were(5.85±0.45)and (6.03±0.42)were higher than that of normal rats,and the difference was significant (P＜0.05);and mRNA levels of μ-opioid receptors in DIO and DR rats((4.51±0.42) and (8.31±0.41) times) were higher than those in normal rats (P＜0.05).The results of Elisa showed that the protein levels of OX-1R in DIO ((2.98±0.28) ng/μl)and DR rats ((3.05±0.31) ng/μl) were higher than those in normal rats ((1.53±0.31) ng/μl,P＜0.05).The content of μ-opioid receptor protein in DR rats ((4.21±0.35) ng/μl) was higher than that of DIO rats ((2.77±0.27) ng/μl),and higher than that of normal rats((1.48±0.32) ng/μ),the difference was significant (P＜0.05).Conclusion BMA orexin-A promotes the spontaneous discharge of GD-sensitive neurons and food intake in normal rats,DIO rats and DR rats,μ-opioid receptors may be involved in the regulation of this process.