Behavioral mechanisms underlying inhibition of food-maintained responding by the cannabinoid receptor antagonist/inverse agonist SR141716A
Behavioral mechanisms underlying inhibition of food-maintained responding by the cannabinoid receptor antagonist/inverse agonist SR141716A
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DOI：
10.1016/j.ejphar.2003.10.012
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发表时间：
2004-01-01
影响因子：
5
通讯作者：
Jentzsch, KR
中科院分区：
文献类型：
--
作者：
De Vry, J;Schreiber, R;Jentzsch, KR
本研究探讨了大麻素CB1受体拮抗剂/反向激动剂N-(哌啶-1-基)-5--(4-chlorophenyl)-1-(2，4-dichlorophenyl)-4-methyl-1-H-pyrazole-3-carboxamide盐酸盐(SR141716A)的厌食作用可能的行为机制。雄性或雌性大鼠被限制饮食，并在每天10分钟的固定比例的食物强化操作过程中训练以发出稳定的反应。在这些条件下，以及在自由饲养条件下，SR141716A抑制食物维持反应(ED50值从0.92到2.52 mg/kg，I.P.)。在相同的手术过程中，SR141716A抑制颅内自我刺激的效力略低于厌食效力(ED50：4.50 mg/kg)。在10分钟的测试期间，SR141716A(1-10 mg/kg)对活动计数没有影响；这表明观察到的对操作行为的抑制并不是运动活动受损的直接结果。然而，SR141716A减弱了条件味觉厌恶范式中的糖精偏好(ED50：6.45 mg/kg)。虽然数据支持SR141716A的厌食作用是由于对食物的奖励效应的减弱，但不能排除药物诱导的厌恶/不适的贡献。(C)2003爱思唯尔B.V.保留所有权利。
This study investigated the possible behavioral mechanisms underlying the anorectic effect of the cannabinoid CB1 receptor antagonist/ inverse agonist N-(piperidin-1-yl)- 5 -(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1-H-pyrazole-3-carboxamide hydrochloride (SR141716A). Male or female rats were food-restricted and trained to emit stable responding in daily 10-min, fixed ratio 10 food-reinforced operant sessions. Under these conditions, as well as under free-feeding conditions, SR141716A inhibited food-maintained responding (ED50 values ranging from 0.92 to 2.52 mg/kg, i.p.). In the same operant procedure, SR141716A suppressed intracranial self-stimulation with a potency which was slightly lower than the anorectic potency (ED50: 4.50 mg/kg). As assessed during a 10-min test period SR141716A (1-10 mg/kg) did not affect activity counts; suggesting that the observed inhibition of operant behavior is not a direct consequence of impairment of locomotor activity. SR141716A, however, attenuated saccharin-preference in a conditioned taste aversion paradigm (ED50: 6.45 mg/kg). Although the data support the suggestion that the anorectic effect of SR141716A results from an attenuating effect on the rewarding effect of food, the contribution of drug-induced aversion/malaise cannot be excluded. (C) 2003 Elsevier B.V All rights reserved.