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

Abstract The effect of continuous ICV infusion of NPFF (10 μg/μl) and morphine (40 μg/μl) 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 [ 3 H][ d -Ala 2 -MePhe 4 ,Glyol 5 ]enkephalin in the homogenate binding experiments and with [ 125 I][ 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.