McLaughlin P J, Winston K M, Limebeer C L, Parker L A, Makriyannis A, Salamone J D
Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA.
Psychopharmacology (Berl). 2005 Jul;180(2):286-93. doi: 10.1007/s00213-005-2171-0. Epub 2005 Mar 15.
A growing body of evidence suggests that cannabinoid CB1 receptor antagonists have potential therapeutic utility as appetite suppressants. However, the specific mechanisms underlying the reduction in food intake produced by these drugs are not well understood.
Considering the known antiemetic and motor-suppressive effects of CB1 agonists, the present studies were conducted to determine if the reductions in food intake induced by the CB1 antagonist AM 251 could result from nausea or impairments in intake-related motor control, rather than solely from appetite suppression.
Three experiments were conducted to examine the effects of AM 251 (2.0, 4.0, or 8.0 mg/kg or vehicle) on detailed parameters of food intake, on the development of conditioned taste avoidance, and on taste reactivity.
In the first experiment, acute administration of AM 251 dose-dependently decreased food intake; nevertheless, feeding rate (grams consumed per time spent eating) and food handling were unaffected, which suggests that food intake was not reduced because of severe motor impairments. In the second experiment, AM 251 dose-dependently reduced intake of a flavor with which it had previously been associated, indicating that conditioned taste avoidance had developed. Lastly, AM 251 was found to induce conditioned rejection reactions in a dose-dependent manner.
The CB1 antagonist AM 251 may reduce food intake in part by inducing nausea or malaise, but not because of incoordination or motor slowing related to feeding.
越来越多的证据表明，大麻素CB1受体拮抗剂作为食欲抑制剂具有潜在的治疗作用。然而，这些药物导致食物摄入量减少的具体机制尚不清楚。
鉴于CB1激动剂已知的止吐和运动抑制作用，开展本研究以确定CB1拮抗剂AM 251引起的食物摄入量减少是否源于恶心或与进食相关的运动控制受损，而非仅仅是食欲抑制。
进行了三项实验，以研究AM 251（2.0、4.0或8.0mg/kg或赋形剂）对食物摄入详细参数、条件性味觉回避形成以及味觉反应性的影响。
在第一个实验中，急性给予AM 251可剂量依赖性地减少食物摄入量；然而，进食速率（每进食时间消耗的克数）和食物处理未受影响，这表明食物摄入量减少并非由于严重的运动障碍。在第二个实验中，AM 251剂量依赖性地减少了与之前关联过的一种味道的摄入量，表明形成了条件性味觉回避。最后，发现AM 251以剂量依赖性方式诱导条件性排斥反应。
CB1拮抗剂AM 251可能部分通过诱导恶心或不适来减少食物摄入量，但并非由于与进食相关的不协调或运动迟缓。
