Amphetamine (AMPH) is a well-known anorectic agent. The mechanism underlying the anorectic response of AMPH has been attributed to its inhibitory effect on hypothalamic neuropeptide Y (NPY), an orexigenic peptide in the brain. However, there is still lack of genomic or in situ immunohistochemical evidence to prove it. The present study was aimed to assess the molecular mechanism of AMPH anorexia by immunostaining of hypothalamic NPY protein in the area of paraventricular nucleus (PVN) and by detecting the change of hypothalamic NPY mRNA level using RT-PCR. Results revealed that an AMPH treatment might reduce the expression of NPY at both transcriptional and posttranslational levels. Comparatively, a treatment of clomipramine, a serotonin transporter inhibitor, was unable to reduce NPY mRNA level, revealing the noninvolvement of hypothalamic NPY gene in serotonin anorexia. Our results provided genomic and in situ immunohistochemical evidence to confirm the mediation of hypothalamic NPY neurons in the anorectic action of AMPH.
