Effect of amphetamine repeated treatment on the feeding behavior in neuropeptide Y-overexpressing mice.

The preset study examined the hypothesis that an increase of brain neuropeptide Y (NPY), an orexigenic peptide, might decrease the action of amphetamine (AMPH), a well-known anorectic agent. Transgenic mice overexpressing the NPY gene were used to compare with the wild-type control. AMPH-induced anorexia is documented to mediate through the release of dopamine (DA), via an activation of D(1)- and D(2)-subtype receptors, to affect the hypothalamic NPY. Thus, co-administration of D(1)/D(2) agonists was also performed to mimic the action of AMPH. The mice of NPY-overexpressing (NPY-OX) and wild-type groups were administered with AMPH or a combination of D(1)/D(2) agonists repeatedly for 5 days. We found that repeated AMPH administration-induced anorexia in wild-type mice was longer (at the initial 3 days) than that in NPY-OX mice (only at the first day). Moreover, repeated co-administration of D(1)/D(2) agonists significantly exerted a continuous anorectic effect in wild-type mice, but exerted a significant effect only at the first day in NPY-OX mice. These results indicated that the anorectic effect of AMPH decayed faster in NPY-OX mice and suggested that NPY expression by the stimuli could counteract the anorectic effect of AMPH. Thus, NPY can be considered to play a functional role in the regulation of AMPH-induced anorexia in mice.