Further evidence for the mediation of both subtypes of dopamine D1/D2 receptors and cerebral neuropeptide Y (NPY) in amphetamine-induced appetite suppression.

Amphetamine (AMPH) is known as an anorectic agent. Repeated treatments of AMPH for several days induced a marked anorexia on day 1 followed by a gradual return of food intake to normal level. Previously, using daily food intake (DFI) as an indicator, we found that both dopamine (DA) D1 and D2 receptors were involved in AMPH anorexia. In the present study, using DFI and body weight change (BWC) as indicators, we took a further step to examine whether repeated co-administrations of D1 and D2 agonists might produce an AMPH-like action. Results revealed that repeated co-administrations of D1 and D2 agonists, but not D1 or D2 agonist alone, produced an AMPH-like action (i.e., tolerant DFI and BWC), confirming the previous study. In addition, we examined whether cerebral neuropeptide Y (NPY), an orexigenic neurotransmitter reported to mediate AMPH anorexia, was involved in the anorectic action of D1/D2 co-administration. Our result revealed that injection of NPY antisense into brain could modify the anorectic action of repeated D1/D2 agonists, indicating the involvement of NPY. Taken together, the present results confirmed that both subtypes of D1 and D2 receptors and cerebral NPY were involved in the anorectic action of AMPH.