Novel Benzodiazepine Receptor Ligands: Palatable Food Intake Following Zolpidem, CGS 17867A, or Ro23-0364, in the Rat

The potent imidazopyridine hypnotic, zolpidem, binds to central benzodiazepine receptors and has predominantly sedative properties, as determine in animal models. In tests of palatable food consumption in nondeprived male rats, the present results indicate that zolpidem (0.3-3.0 mg/kg) had no effect on food intake. Its lack of effect contrasts sharply with other benzodiazepine agonists which strongly stimulate palatable food intake. Two other novel compounds, both of which bind to benzodiazepine receptors, and which have reduced propensity to induce sedative effects, increased palatable food consumption, although in differing ways. The imidazobenzodiazepine Ro23-0364 (0.3-10.0 mg/kg) dose-dependently increased feeding in the standard procedure, but failed to stimulate food intake in presatiated animals. The pyrazoloquinoline CGS 17867A (1.0-30.0 mg/kg) increased food intake in both test procedures, although the dose-effect relationship was nonmonotonic. Taken together, the data indicate a probable separation between hyperphagic and sedating effects of benzodiazepine receptor agonists. If zolpidem's sedative effect is linked to an action at a receptor subtype (benzodiazepine Type 1 or omega 1), then the hyperphagic effect of benzodiazepines may depend more on the alternative subtype.