Downregulation of Mu-opioid binding sites following chronic administration of neuropeptide FF (NPFF) and morphine

The effect of continuous ICV infusion of NPFF (10 mu g/mu l) and morphine (40 mu g/mu l) on mu-opioid binding sites was examined in rats using the in vitro radiolabeled techniques of whole-brain homogenate receptor binding and quantitative autoradiography. Mu receptors were labeled with [H-3] [D-Ala(2)-MePhe(4),Glyol(5)] enkephalin in the homogenate binding experiments and with [I-125][D-Ala(2)-MePhe(4),Gly-ol(5)] enkephalin in autoradiographic studies. In homogenate binding studies, chronic administration of NPFF or morphine significantly downregulated mu receptors by 20% and 44%, respectively. Quantitative autoradiographic experiments demonstrated downregulation of mu opioid receptors in specific brain nuclei for both NPFF- and morphine-treated animals. Within the striatum and several nuclei of the thalamus, the mu receptors of the NPFF- and morphine-treated animals were decreased by 20-30% and 38-73%, respectively. These results suggest that NPFF may modulate opioid-mediated responses in part by altering the density of mu-opioid receptors.