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Increased cannabinoid CB 1 receptor binding and activation of GTP‐binding proteins in the basal ganglia of patients with Parkinson's syndrome and of MPTP‐treated marmosets
Author(s) -
LastresBecker I.,
Cebeira M.,
Ceballos M.L.,
Zeng B. Y.,
Jenner P.,
Ramos J. A.,
FernándezRuiz J. J.
Publication year - 2001
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.0953-816x.2001.01812.x
Subject(s) - putamen , globus pallidus , basal ganglia , gtpgammas , mptp , substantia nigra , caudate nucleus , medicine , endocrinology , cannabinoid , cannabinoid receptor , neuroscience , parkinson's disease , agonist , chemistry , receptor , biology , central nervous system , disease
Recent evidence obtained in rat models of Parkinson's disease showed that the density of cannabinoid CB 1 receptors and their endogenous ligands increase in basal ganglia. However, no data exists from post‐mortem brain of humans affected by Parkinson's disease or from primate models of the disorder. In the present study, we examined CB 1 receptor binding and the magnitude of the stimulation by WIN55,212‐2, a specific CB 1 receptor agonist, of [ 35 S]GTPγS binding to membrane fractions from the basal ganglia of patients affected by Parkinson's disease. In Parkinson's disease, WIN55,212‐2‐stimulated [ 35 S]GTPγS binding in the caudate nucleus, putamen, lateral globus pallidus and substantia nigra was increased, thus indicating a more effective activation of GTP‐binding protein‐coupled signalling mechanisms via CB 1 receptors. This was accompanied by an increase in CB 1 receptor binding in the caudate nucleus and the putamen, although no changes were observed in the lateral globus pallidus and the substantia nigra. Because Parkinson's disease patients had been chronically treated with l ‐DOPA, brains were studied from normal common marmosets and 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated animals with and without chronic L‐DOPA treatment. MPTP‐lesioned marmosets had increased CB 1 receptor binding in the caudate nucleus and the putamen compared to control marmosets, as well as increased stimulation of [ 35 S]GTPγS binding by WIN55,212‐2. However, following l ‐DOPA treatment these parameters returned towards control values. The results indicate that a nigro‐striatal lesion is associated with an increase in CB 1 receptors in the basal ganglia in humans and nonhuman primates and that this increase could be reversed by chronic l ‐DOPA therapy. The data suggest that CB 1 receptor blockade might be useful as an adjuvant for the treatment of parkinsonian motor symptoms.