Verty A N A, McFarlane J R, McGregor I S, Mallet P E
School of Psychology, University of New England, Armidale, NSW 2351, Australia.
Neuropharmacology. 2004 Sep;47(4):593-603. doi: 10.1016/j.neuropharm.2004.06.002.
Oxytocin and CB(1) cannabinoid receptors independently modulate food intake. Although an interaction between oxytocin and cannabinoid systems has been demonstrated with respect to the cannabinoid withdrawal syndrome, the interaction between these systems in modulating food intake has not yet been examined. The present study had three primary purposes: (1) to determine whether oxytocin and a CB(1) receptor antagonist block food and fluid intake in a supra-additive manner, (2) to determine the relative position of the CB(1) receptors in the chain of control of food intake in relation to the oxytocin system, and (3) to determine whether the increase in fluid intake induced by an oxytocin antagonist is mediated via cannabinoid receptors. Rats were habituated to the test environment and injection procedure, and then received intracerebroventricular (ICV) injections of various combinations of the oxytocin receptor antagonist tocinoic acid, the cannabionid receptor agonist delta(9)-tetrahydrocannabinol (THC), oxytocin, or the cannabinoid receptor antagonist SR 141716. Food and water intake and locomotor activity were then measured for 120 min. When administrated alone, SR 141716 and oxytocin dose-dependently attenuated baseline food intake, while oxytocin but not SR 141716 reduced water intake. Sub-anorectic doses of SR 141716 and oxytocin attenuated baseline feeding beyond what would be expected by the sum of the individual drug effects without affecting baseline water intake. THC stimulated feeding but not water intake. THC-induced feeding was not blocked by oxytocin, however, the oxytocin did attenuate water intake during such feeding. SR 141716 dose-dependently reduced tocinoic-acid-stimulated food intake and partially attenuated water intake. Locomotor activity was not significantly affected by any drug treatments, suggesting that effects on feeding were not due to a non-specific reduction in motivated behaviour. These findings reveal an interaction between cannabinoid and oxytocin systems in food intake. Results further reveal that the oxytocin system effects on water intake are partially mediated via CB(1) receptors, CB(1) receptors are located downstream from oxytocin receptors, and CB(1) receptor signalling is necessary to prevent oxytocin from altering food intake.
催产素和大麻素CB(1)受体独立调节食物摄入量。尽管已证实催产素与大麻素系统在大麻素戒断综合征方面存在相互作用，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。本研究有三个主要目的：(1) 确定催产素和一种CB(1)受体拮抗剂是否以超相加的方式阻断食物和液体摄入；(2) 确定CB(1)受体在与催产素系统相关的食物摄入控制链中的相对位置；(3) 确定催产素拮抗剂诱导的液体摄入量增加是否通过大麻素受体介导。大鼠适应测试环境和注射程序，然后接受脑室注射催产素受体拮抗剂托西酸、大麻素受体激动剂δ(9)-四氢大麻酚(THC)、催产素或大麻素受体拮抗剂SR 141716的各种组合。然后测量120分钟内的食物和水摄入量以及运动活动。单独给药时，SR 141716和催产素剂量依赖性地减弱基线食物摄入量，而催产素而非SR 141716减少水摄入量。亚厌食剂量的SR 141716和催产素减弱基线进食量，超过单独药物作用之和预期的量，且不影响基线水摄入量。THC刺激进食但不刺激水摄入。催产素不阻断THC诱导的进食，但催产素确实会在这种进食过程中减弱水摄入量。SR 141716剂量依赖性地减少托西酸刺激的食物摄入量，并部分减弱水摄入量。任何药物治疗均未显著影响运动活动，表明对进食的影响并非由于动机行为的非特异性降低。这些发现揭示了大麻素和催产素系统在食物摄入方面的相互作用。结果进一步表明，催产素系统对水摄入的影响部分通过CB(1)受体介导，CB(1)受体位于催产素受体下游，且CB(1)受体信号传导对于防止催产素改变食物摄入量是必要的。
