Chronic exposure to antibodies directed against anti-opiate peptides alter delta-opioid receptor levels.
The development of addictive states in response to chronic opioid use may be regulated partially by the release of endogenous peptides. These anti-opiate peptides (AOP) are secreted or released into the CNS and produce diverse actions that counterbalance the effects of prolonged opiate exposure. Though the mechanism(s) by which these peptides exert their physiological properties remain largely unknown, there is some indication that AOP's modulate opioid receptor levels. In this study, we investigated the effects of chronically infused alpha-melanocyte stimulating hormone (alpha-MSH), dynorphin(1-8) (DYN(1-8)), dynorphin A (DYNA), and NPFF antibodies on delta-opioid receptor expression in rat brains. Quantitative autoradiographic experiments revealed that antibodies directed against alpha-MSH and DYNA produced significant increases in delta receptor levels in the caudate, claustrum, and cingulate cortex of the rat brain. Conversely, NPFF monoclonal antibodies caused significant decreases in the caudate, nucleus accumbens, olfactory tubercle, and cingulate cortex. These results suggest that the density of delta-opioid receptors is affected by changes in the levels of the anti-opioid peptides in the extracelluar fluid in the rat brain.
Goodman
C B
CB
Florida A&M University, College of Pharmacy and Pharmaceutical Sciences, Tallahassee, FL 32303, USA. cgoodman@famu.edu
Heyliger
S
S
Emilien
B
B
Partilla
J S
JS
Yang
H Y
HY
Lee
C H
CH
Cadet
J L
JL
Rothman
R B
RB
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D001345:Autoradiography; D001921:Brain / Q000378:metabolism; D004399:Dynorphins / Q000037:antagonists & inhibitors / Q000276:immunology; D008297:Male; D009292:Narcotic Antagonists / Q000276:immunology*; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000276:immunology; D018847:Opioid Peptides / Q000037:antagonists & inhibitors* / Q000276:immunology*; D009293:Opioid-Related Disorders / Q000209:etiology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D014018:Tissue Distribution; D000521:alpha-MSH / Q000037:antagonists & inhibitors / Q000276:immunology
D000906:Antibodies; D009292:Narcotic Antagonists; D009842:Oligopeptides; D018847:Opioid Peptides; D010446:Peptide Fragments; D017465:Receptors, Opioid, delta; D000521:alpha-MSH; D004399:Dynorphins; C026770:dynorphin (1-8); C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide