Phenylpropanolamine (PPA) is an appetite suppressant. Repeated treatment with PPA can decrease food intake on initial days, which is followed by a gradual return of normal food intake (tolerant effect) on subsequent days. In an attempt to investigate the underlying mechanisms of PPA tolerance, roles of catecholamine (CAT) and hypothalamic NPY genome were examined. Results revealed that pretreatment with either bupropion, a CAT transporter inhibitor, or alpha-methyl-para-tyrosine, a tyrosine hydroxylase inhibitor, could modulate the effect of PPA tolerance. Moreover, results also revealed that the alteration in NPY mRNA level coincided with the change of feeding behavior during PPA treatment and that infusions of NPY antisense oligonucleotide into cerebroventicle could abolish the effect of PPA tolerance. Our current findings suggest that cerebral CAT and hypothalamic NPY genome are involved in the development of tolerance to PPA-induced appetite suppression.
