Lack of the involvement of mu1-opioid receptor subtype on motivational effects induced by the endogenous mu-opioid receptor ligands endomorphin-1 and -2 in the mouse.
The present study was designed to investigate the role of mu-opioid receptor subtypes in the motivational effect of endogenous mu-opioid receptor ligands, endomorphin-1 and -2. In C57BL/6J mice, endomorphin-1 produced a significant place preference, whereas endomorphin-2 exhibited a significant place aversion. These effects were abolished by a mu1/mu2-opioid receptor antagonist beta-funaltrexamine. Under these conditions, both endomorphin-1 and -2 produced their motivational effects in mu1-opioid receptor-deficient CXBK mice, indicating the mu2-opioid receptor involvement. Furthermore, in the lower midbrain including ventral tegmental area, both endomorphin-1 and -2 equally produced dose-related increases in guanosine-5'-o-(3-[35S] thio) triphosphate bindings in C57BL/6J and CXBK mice. These findings indicate that endomorphin-1 and -2 may produce distinct motivational effects via respective mu2-opioid receptor isoforms in the mouse. Furthermore, endomorphin-1 and -2 produced the mu1-resistant G-protein activation in the mouse lower midbtrain.
Narita
M
M
Department of Toxicology, School of Pharmacy, Hoshi University, 2-4-41 Ebara Shinagawa-Ku, 142-8501, Tokyo, Japan.
Ozaki
S
S
Ioka
M
M
Mizoguchi
H
H
Nagase
H
H
Tseng
L F
LF
Suzuki
T
T
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009042:Motivation; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology*; D011869:Radioligand Assay; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013462:Sulfur Radioisotopes / Q000493:pharmacokinetics; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; D013462:Sulfur Radioisotopes; C105293:endomorphin 1; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C105294:endomorphin 2; D009271:Naltrexone; C024524:beta-funaltrexamine; D019204:GTP-Binding Proteins