Roles of central catecholamine and hypothalamic neuropeptide Y genome in the development of tolerance to phenylpropanolamine-mediated appetite suppression.

Phenylpropanolamine (PPA) is an appetite suppressant. Repeated treatment with PPA can decrease food intake on initial days, but on subsequent days, food intake gradually returns to normal (tolerant effect). In an attempt to investigate the underlying mechanisms of PPA tolerance, the authors examined the roles of catecholamine (CAT) and hypothalamic neuropeptide Y (NPY) genome. Results revealed that pretreatment with either bupropion, a CAT transporter inhibitor, or a-methylparatyrosine, a tyrosine hydroxylase inhibitor, modulated the effect of PPA tolerance. Moreover, results also revealed that the alteration in NPY messenger RNA level coincided with the change of feeding behavior during PPA treatment and that infusions of NPY antisense oligonucleotide into the cerebroventricle abolished the effect of PPA tolerance. These findings suggest that cerebral CAT and hypothalamic NPY genome are involved in the development of tolerance to PPA-induced appetite suppression.