Cooper S J, Moores W R
Pharmacol Biochem Behav. 1985 Aug;23(2):169-72. doi: 10.1016/0091-3057(85)90551-9.
Nondeprived male rats were familiarized with 30 min daily access to a highly palatable diet. Clonazepam, midazolam and chlordiazepoxide each produced significant dose-dependent increases in food consumption. Clonazepam was the most potent, and a significant hyperphagic effect was detected following 0.078 mg/kg (IP). Amongst novel non-benzodiazepine anxiolytics, zopiclone and CL 218,872 also produced significant increases in food intake. The smallest doses to produce significant hyperphagia for these two drugs were 10.0 and 2.5 mg/kg (IP) respectively. In contrast, tracazolate caused only a reduction in feeding, evident at 20 and 40 mg/kg (IP). Previous reports indicate that although benzodiazepines, zopiclone and CL 218,872 displace [3H] flunitrazepam binding in rat cerebral cortex preparations, tracazolate enhances the binding. Our results are consistent with the drug-induced hyperphagia depending upon agonist actions at high-affinity benzodiazepine sites. They also provide pharmacological evidence for a dissociation between hyperphagic and anxiolytic drug effects. Phenobarbital (2.5-40.0 mg/kg), like the benzodiazepines, produced a strong stimulation of food intake, indicating that drug action at an alternative site in the benzodiazepine receptor-GABA receptor-chloride channel complex can also lead to hyperphagia.
未被剥夺食物的雄性大鼠每天有30分钟可自由摄取美味食物，以此使其熟悉这种情况。氯硝西泮、咪达唑仑和氯氮卓均能显著增加食物摄入量，且呈剂量依赖性。氯硝西泮作用最强，腹腔注射0.078mg/kg后即可检测到显著的摄食亢进效应。在新型非苯二氮䓬类抗焦虑药中，佐匹克隆和CL 218,872也能显著增加食物摄入量。这两种药物产生显著摄食亢进的最小剂量分别为腹腔注射10.0mg/kg和2.5mg/kg。相比之下，曲卡唑酯仅能减少进食，腹腔注射20mg/kg和40mg/kg时这种作用明显。先前的报道表明，虽然苯二氮䓬类药物、佐匹克隆和CL 218,872能取代大鼠大脑皮层制剂中[3H]氟硝西泮的结合，但曲卡唑酯能增强这种结合。我们的结果与药物诱导的摄食亢进取决于高亲和力苯二氮䓬位点的激动剂作用一致。它们还为摄食亢进和抗焦虑药物作用之间的分离提供了药理学证据。苯巴比妥（2.5 - 40.0mg/kg）与苯二氮䓬类药物一样，能强烈刺激食物摄入，这表明药物作用于苯二氮䓬受体 - GABA受体 - 氯离子通道复合物的另一个位点也可导致摄食亢进。
