EFFECTS ON FOOD AND WATER-INTAKE OF THE ALPHA-1-ADRENOCEPTOR AGONISTSAMIDEPHRINE AND SK-AND-F-89748

Activation of alpha-1 adrenoceptors, via systemic injection of agonist s such as cirazoline and phenylpropanolamine (PPA), reliably suppresse s food intake in rats. These effects are thought to result from stimul ation of central alpha1-adrenoceptors within the rat paraventricular h ypothalamic nucleus (PVN), based on studies in which direct injections of cirazoline, methoxamine, phenylephrine and PPA into PVN suppress f ood intake. Because relatively few alpha-1-agonists have been tested t o date using the systemic route of exposure, the present study examine d the effects of the alpha1-adrenoceptor agonists amidephrine and SKF- 89748 on food and water intake. Adult male rats received systemic inje ctions (IP) of either amidephrine (0.025, 0.05, 0.01 mg/kg) or of SK&F 89748 (0.01, 0.02, and 0.04 mg/kg). Amidephrine markedly suppressed f ood intake (ED50=0.49 mg/kg) and water intake (ED50=0.50 mg/kg), while SK&F 89748 marginally suppressed food intake (ED50=0.37 mg/kg) and wa s less potent in suppressing water intake (ED50=0.76 mg/kg). These res ults document that systemic injection of the alpha1-adrenoceptor agoni sts amidephrine and SK&F 89748 induces anorexia with amidephrine exert ing greater potency than SK&F 89748. These results further support the hypothesis that stimulation of alpha1-adrenoceptors suppresses food i ntake.