The cannabinoid CB1 antagonist AM 251 produces food avoidance and behaviors associated with nausea but does not impair feeding efficiency in rats
The cannabinoid CB1 antagonist AM 251 produces food avoidance and behaviors associated with nausea but does not impair feeding efficiency in rats
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DOI：
10.1007/s00213-005-2171-0
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发表时间：
2005-07-01
影响因子：
3.4
通讯作者：
Salamone, JD
中科院分区：
文献类型：
--
作者：
McLaughlin, PJ;Winston, KM;Salamone, JD
理由：越来越多的证据表明大麻素CB 1受体拮抗剂作为食欲抑制剂具有潜在的治疗效用。然而，这些药物减少食物摄入量的具体机制尚不清楚。目的：考虑到已知的CB 1激动剂的止吐和运动抑制作用，本研究旨在确定CB 1拮抗剂AM 251引起的摄食量减少是否可能是由于恶心或与摄食相关的运动控制障碍，而不仅仅是由于食欲抑制。研究方法：进行了三个实验来检查AM 251（2.0、4.0或8.0 mg/kg或媒介物）对食物摄入的详细参数、对条件性味觉回避的发展和对味觉反应性的影响。结果如下：在第一个实验中，急性施用AM 251剂量依赖性地减少食物摄入;然而，进食速率（每次进食消耗的克数）和食物处理不受影响，这表明食物摄入没有因为严重的运动障碍而减少。在第二个实验中，AM 251剂量依赖性地减少了以前与之相关的风味的摄入，表明条件性味觉回避已经发展。最后，发现AM 251以剂量依赖性方式诱导条件性排斥反应。结论：CB 1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，但不是因为与进食相关的不协调或运动减慢。
Rationale: 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. Objective: 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-relatedmotor control, rather than solely from appetite suppression. Methods: 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. Results: 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, AM251 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. Conclusions: 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.