Bidirectional changes in the consumption of food produced by beta-carbolines

beta-Carboline derivatives provide examples of benzodiazepine receptor ligands which span the range: full agonist-partial agonist-antagonist-partial inverse agonist-full inverse agonist. Taken together, the effects of these compounds illustrate two important principles: firstly, the bidirectionality of effects which can be achieved using benzodiazepine receptor ligands; secondly, the selectivity of effects which are produced by partial agonists. Applied to the study of feeding processes, these principles imply that both hyperphagic and anorectic effects can be generated by actions of selected ligands at benzodiazepine receptors. Furthermore, they suggest that a hyperphagic effect may occur in the absence of side-effects (e.g., sedation, muscle-relaxation), which are characteristic of classical benzodiazepines. Experimental data in support of these predictions are presented. A microstructural approach to feeding behavior indicated that a benzodiazepine receptor agonist and an inverse agonist extend and abbreviate, respectively, the duration of individual bouts of eating. Preference for a saccharin solution was attenuated by the beta-carboline inverse agonist, FG 7142, but rejection of a quinine solution was not increased. Adrenalectomy had no effect on the anorectic effect of inverse agonists.