Verty A N A, McFarlane J R, McGregor I S, Mallet P E
School of Psychology, University of New England, Armidale, New South Wales 2351, Australia.
Endocrinology. 2004 Jul;145(7):3224-31. doi: 10.1210/en.2004-0059. Epub 2004 Mar 19.
Melanocortin receptor 4 (MCR4) and CB(1) cannabinoid receptors independently modulate food intake. Although an interaction between the cannabinoid and melanocortin systems has been found in recovery from hemorrhagic shock, the interaction between these systems in modulating food intake has not yet been examined. The present study had two primary purposes: 1) to examine whether the cannabinoid and melanocortin systems act independently or synergistically in suppressing food intake; and 2) to determine the relative position of the CB(1) receptors in the chain of control of food intake in relation to the melanocortin system. Rats were habituated to the test environment and injection procedure and then received intracerebroventicular injections of various combinations of the MCR4 receptor antagonist JKC-363, the CB(1) receptor agonist Delta(9)-tetrahydrocannabinol, the MCR4 receptor agonist alpha-MSH, or the cannabinoid CB(1) receptor antagonist SR 141716. Food intake and locomotor activity were then recorded for 120 min. When administrated alone, SR 141716 and alpha-MSH dose-dependently attenuated baseline feeding, whereas sub-anorectic doses of SR 141716 and alpha-MSH synergistically attenuated baseline feeding when combined. Delta(9)-Tetrahydrocannabinol-induced feeding was not blocked by alpha-MSH, whereas SR 141716 dose-dependently attenuated JKC-363-induced feeding. Locomotor activity was not significantly affected by any drug treatment, suggesting that the observed effects on feeding were not due to a nonspecific reduction in motivated behavior. These findings revealed a synergistic interaction between the cannabinoid and melanocortin systems in feeding behavior. These results further suggested that CB(1) receptors are located downstream from melanocortin receptors and CB(1) receptor signaling is necessary to prevent the melanocortin system from altering food intake.
黑皮质素受体4（MCR4）和大麻素CB(1)受体可独立调节食物摄入量。尽管在失血性休克恢复过程中发现了大麻素系统与黑皮质素系统之间存在相互作用，但尚未研究这两个系统在调节食物摄入量方面的相互作用。本研究有两个主要目的：1）研究大麻素系统和黑皮质素系统在抑制食物摄入量方面是独立发挥作用还是协同发挥作用；2）确定CB(1)受体在与黑皮质素系统相关的食物摄入控制链中的相对位置。将大鼠置于测试环境并使其适应注射程序，然后向其脑室内注射MCR4受体拮抗剂JKC - 363、CB(1)受体激动剂Δ9 - 四氢大麻酚、MCR4受体激动剂α - 促黑素或大麻素CB(1)受体拮抗剂SR 141716的各种组合。然后记录120分钟内的食物摄入量和运动活动。单独给药时，SR 141716和α - 促黑素能剂量依赖性地减弱基础摄食，而亚厌食剂量的SR 141716和α - 促黑素联合使用时能协同减弱基础摄食。Δ9 - 四氢大麻酚诱导的摄食不受α - 促黑素的阻断，而SR 141716能剂量依赖性地减弱JKC - 363诱导的摄食。任何药物处理对运动活动均无显著影响，这表明观察到的对摄食的影响并非由于动机行为的非特异性降低所致。这些发现揭示了大麻素系统与黑皮质素系统在摄食行为中存在协同相互作用。这些结果进一步表明，CB(1)受体位于黑皮质素受体的下游，且CB(1)受体信号传导对于防止黑皮质素系统改变食物摄入量是必要的。
