Opiate receptor avidity is reduced in non-motor impaired MPTP-lesioned rhesus monkeys.
Opiate receptor avidity, roughly equivalent to the ratio of unoccupied receptor density to the receptor dissociation constant (B'max/KD), was measured in four MPTP (1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine)-lesioned rhesus monkeys and nine normal controls with positron emission tomography (PET) and 6-deoxy-6-beta-[18F]fluoronaltrexone (cyclofoxy, CF), a mu- and kappa-opiate receptor antagonist. Although the MPTP-lesioned monkeys were dopamine deficient as measured with [18F]-L-fluorodopa ([18F]-DOPA) and PET [Doudet et al., 6-[18F]-L-DOPA imaging of the dopamine neostriatal system in normal and clinically normal-MPTP-treated rhesus monkeys, Exp. Brain Res. 78 (1989) 69-80], they had clinically recovered from the acute motor effects of MPTP exposure. Opiate receptor avidity was found to be reduced by 30-35% in the opiate-receptor rich areas of caudate, anterior putamen, thalamus, and amygdala of the MPTP-lesioned animals. The results suggest that opiate pathways make a significant contribution to the adjustment of cortico-striatal-thalamic pathway activity and thereby to behavior in rhesus monkeys following dopamine loss.
Cohen
R M
RM
Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bldg. 36, Room 1A05, 36 Convent Dr. MSC 4030, Bethesda, MD 20892-4030, USA. bob@shiloh.nimh.nih.go
Carson
R E
RE
Aigner
T G
TG
Doudet
D J
DJ
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008253:Macaca mulatta; D009271:Naltrexone / Q000031:analogs & derivatives; D009292:Narcotic Antagonists; D011957:Receptors, Opioid / Q000378:metabolism*; D012016:Reference Values; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D015259:Dopamine Agents; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009271:Naltrexone; C066758:6-deoxy-6-fluoronaltrexone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine