侧脑室微量注射大麻素受体拮抗剂对orexin-A诱导大鼠能量代谢改变的影响及潜在机制研究

目的:探讨大麻素1型受体(CB1)抑制剂利莫那班对下丘脑外侧区(LHA)微量注射orexin-A诱导的小鼠能量代谢及相关行为变化改变的影响。方法:通过侧脑室微量注射(icv)利莫那班,同时LHA微量注射orexin-A,测量小鼠能量代谢、自主运动的变化,杏仁核(CeA)内多巴胺释放能力以及小鼠摄食量的变化。结果:侧脑室微量注射利莫那班可减弱因LHA微量注射orexin-A引起的小鼠能量代谢变化,降低小鼠自主运动,并且减弱小鼠CeA内多巴胺释放能力。注射(icv)利莫那班未改变LHA微量注射orexin-A所诱导的摄食量增多。此外,LHA双侧注射利莫那班可阻断LHA内注射orexin-A对运动活性的促进作用,但不影响小鼠的摄食量。结论:大麻素受体涉及orexin-A诱导的小鼠中脑边缘系统多巴胺系统活化的调控,对能量代谢及自主运动也有影响,但对食物摄入的调节无明显影响。

Effect of Intracerebroventricular Microinjection of Ephedrine Receptor Antagonist on Energy Metabolism Induced by Orexin-A in Rats and Its Potential Mechanism

ABSTRACT Objective: To investigate the effects of the cannabinoid type 1 receptor (CB1) inhibitor rimonabant on the energy metabolism and related behavioral changes induced by microinjection of orexin-A into the lateral hypothalamic area (LHA). Methods: Microinjection of rimonabant into the lateral ventricle (icv) and microinjection of orexin-A into LHA were used to measure changes in energy metabolism, autonomous movement, dopamine release in the amygdala (CeA), and changes in food intake in mice. Results: The results showed that microinjection of rimonabant into lateral ventricle could attenuate the changes of energy metabolism induced by microinjection of orexin-A into LHA, decrease the spontaneous movement of mice, and weaken the ability of dopamine release in CeA of mice. Rimonabant injection of (icv) did not change the increase of food intake induced by microinjection of orexin-A into LHA. In addition, it was found that bilateral injection of rimonabant into LHA could block the promoting effect of orexin-A injection into LHA on exercise activity, but did not affect the food intake of mice. Conclusion: Cannabinoid receptors are involved in orexin-A-induced regulation of dopaminergic system activation in the midbrain system of mice, and have an effect on energy metabolism and autonomic movement, but have no significant effect on food intake regulation.