Opiate receptor avidity is reduced bilaterally in rhesus monkeys unilaterally lesioned with MPTP

Opiate receptor avidity (unoccupied receptor density / the receptor dissoci ation constant), was measured in four animals with unilateral parkinsonian symptoms following MPTP ( 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) inf usions into the internal carotid of one side, and nine normal controls with positron emission tomography (PET) and 6-deoxy-6-beta-[F-18] fluoronaltrex one (cyclofoxy, CF), a mu- and kappa-opiate receptor antagonist. PET studie s of 6-[F-18] -L-fluoro-L-3,4-dihydroxyphenylalanine ([F-18]-DOPA) in these parkinsonian animals, although documenting the primarily unilateral nature of the lesion, also demonstrated a milder loss of dopaminergic on the side opposite the infusion. Opiate receptor avidity was found to be reduced by 20-34% in the caudate, anterior putamen, thalamus, and amygdala of these pr imarily unilaterally MPTP-exposed animals, bilaterally with no statisticall y significant differences between the two sides. The affected regions are t he same as those previously demonstrated to have a 30-35% loss in clinicall y recovered bilaterally MPTP-lesioned animals. These findings confirm that the opiate pathway can change in response to modest decreases in basal gang lia dopamine innervation. Thus, opiate pathway adaptation is likely to cont ribute to the dynamic changes in basal ganglia circuits that forestall the initial clinical manifestations of Parkinson's disease. In addition, opiate pathway(s) may contribute to the treatment responsiveness and progression of the disease either directly through effects on basal ganglia function or indirectly through effects on basal ganglia plasticity. Synapse 33:282-288 , 1999. (C) 1999 Wiley-Liss, Inc.