Suppression of feeding induced by phenylephrine microinjections within the paraventricular hypothalamus in rats

Abstract

Rats were treated with the alpha-2 agonist clonidine (4, 20 and 50 nMol) and with the alpha-1 agonist 1-phenylephrine (50, 100, 200 and 400 nMol). Phenylpropanolamine (PPA) is a phenythylamine anorectic drug that exerts direct agonist effects predominantly on alpha-1 adrenergic receptors, with some alpha-2 adrenergic activity. We recently reported that injection of PPA significantly suppressed feeding in rats. Prior studies have noted that into the paraventricular hypothalamus (PVN) microinjections of the alpha-2 adrenergic receptor agonist clonidine into the PVN induced feeding behavior in satiated rats. However, the effect on feeding of administration of alpha-1 adrenergic agonists within the PVN remains unknown. In the present study, unilateral guide cannulae aimed at the PVN were surgically implanted in adult male rats. In an initial 60 min feeding test conducted under free-feeding ("non-deprived") conditions, each rat was found to eat significantly more food after injection of 25 nMol norepinephrine (NE) into the PVN. In subsequent tests, the feeding increased significantly to 4 nMol clonidine; however, feeding was suppressed by 50 nMol clonidine. Food intake after 20 nMol clonidine was not significantly different from that recorded after vehicle. In contrast, phenylephrine (100-400 nMol) reliably suppressed feeding behavior. In the final phase of the study, the rats ate significantly less food after injection of 160 nMol PPA into the PVN but consumed significantly more food after a final injection of 25 nMol NE into the PVN. These results suggest that the anorexic action of PPA may be linked to activation of alpha-1 adrenergic receptors within the PVN.