Hyperphagic and anorectic effects of beta-carbolines in a palatable food consumption test: comparisons with triazolam and quazepam.
The triazolobenzodiazepine triazolam (0.1-1.0 mg/kg i.p.) and quazepam (0.3-30.0 mg/kg i.p.) were administered to non-food-deprived rats which had been partially-satiated on a palatable diet. In a subsequent 30 min feeding test, both compounds produced a significant increase in the level of food consumption. While triazolam had a dose-related effect and produced a 151.5% increase in the level of food intake, quazepam exerted only a partial effect, achieving a 73.9% increase in food intake at 3.0 mg/kg but no additional increase in food intake at higher doses. The two beta-carbolines, ZK 93423 (0.1-3.0 mg/kg i.p.) and ZK 91296 (1.0-30.0 mg/kg i.p.), a full agonist and a partial agonist at benzodiazepine receptors respectively, also produced significant increases in food consumption under the same experimental conditions. ZK 93423 had effects which were similar to those of triazolam, ZK 91296 had effects similar to quazepam. The beta-carboline benzodiazepine inverse agonist FG 7142 (10.0 mg/kg i.p.) had an anorectic effect in non-food-deprived rats given 30 min access to the highly palatable diet. This effect was reversed by the beta-carboline benzodiazepine receptor antagonist ZK 93426 in a dose-dependent manner. These results emphasize that within the series of beta-carboline ligands for benzodiazepine receptors, their characterization in terms of agonists, antagonists and inverse agonists has validity with respect to the behavioural response of palatable food consumption in non-food-deprived rats.
D000818:Animals; D014151:Anti-Anxiety Agents; D001067:Appetite Depressants / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D014229:Triazolam / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D001067:Appetite Depressants; D002243:Carbolines; D011720:Pyrazoles; D001569:Benzodiazepines; D014229:Triazolam; C035874:FG 7142; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one; C038933:ZK 91296; C042568:ZK 93426; C025130:quazepam