Suppression of feeding, drinking, and locomotion by a putative cannabinoid receptor 'silent antagonist'
Suppression of feeding, drinking, and locomotion by a putative cannabinoid receptor 'silent antagonist'
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DOI：
10.1016/j.ejphar.2005.11.032
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发表时间：
2006-01-13
影响因子：
5
通讯作者：
Mallet, PE
中科院分区：
文献类型：
--
作者：
Gardner, A;Mallet, PE
本研究比较了大麻素受体沉默拮抗剂O-141716和大麻素受体反向激动剂SR 141716对小鼠食物和水的消耗以及运动能力的影响。未剥夺雄性Wistar大鼠习惯于该仪器和测试程序，然后在4h测试前腹腔注射赋形剂、O-141716(0.03~3.0 mg/kg)或SR 141716(3.0 mg/kg)。这两种药物都显著减少了食物的消耗。只有在O-2050之前，水的摄入量和运动能力才显著减少。结果支持这样的观点，即大麻素受体拮抗剂通过阻断内源性大麻素促氧信号来抑制取食行为，而不是通过大麻素受体的反向激动剂。然而，还需要进一步的研究来证实O-2050是一种不具有反向激动剂特性的大麻素CB1受体拮抗剂。(C)2005 Elsevier B.V.保留所有权利。
This study compared the effects of the putative cannabinoid receptor 'silent antagonist' O-2050 with the cannabinoid receptor inverse agonist SR 141716 on food and water consumption, and locomotor activity. Non-deprived male Wistar rats were habituated to the apparatus and testing procedures, then injected intraperitoneally with vehicle, O-2050 (0.03-3.0 mg/kg), or SR 141716 (3.0 mg/kg) prior to 4-h test sessions. Food consumption was significantly reduced by both drugs. Water intake and locomotor activity were significantly reduced only by O-2050. Results support the notion that cannabinoid receptor antagonists suppress feeding behaviour by blocking an endogenous cannabinoid orexigenic signal, rather than by inverse agonism at cannabinoid receptors. However, further studies are needed to confirm the status of O-2050 as a cannabinoid CB1 receptor antagonist devoid of inverse agonist properties. (c) 2005 Elsevier B.V. All rights reserved.