Downregulation of mu-opioid binding sites following chronic administration of neuropeptide FF (NPFF) and morphine.
The effect of continuous ICV infusion of NPFF (10 micrograms/microliter) and morphine (40 micrograms/microliter) 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 [3H][D-Ala2-MePhe4,Glyol5] enkephalin in the homogenate binding experiments and with [125I][D-Ala2-MePhe4,Gly-ol5]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.
Goodman
C B
CB
Clinical Psychopharmacology Section, NIH, NIDA, Baltimore, MD 21224, USA.
Emilien
B
B
Becketts
K
K
Cadet
J L
JL
Rothman
R B
RB
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects; D015536:Down-Regulation; D004333:Drug Administration Routes; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013347:Subcellular Fractions / Q000378:metabolism; D013788:Thalamus / Q000187:drug effects; D014018:Tissue Distribution
D000701:Analgesics, Opioid; D004745:Enkephalins; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide