Involvement of sensorimotor, limbic, and associative basal ganglia domains in L-3,4-dihydroxyphenylalanine-induced dyskinesia.
Dyskinesia represents a debilitating complication of L-3,4-dihydroxyphenylalanine (L-dopa) therapy for Parkinson's disease. Such motor manifestations are attributed to pathological activity in the motor parts of basal ganglia. However, because consistent funneling of information takes place between the sensorimotor, limbic, and associative basal ganglia domains, we hypothesized that nonmotor domains play a role in these manifestations. Here we report the changes in 2-deoxyglucose (2-DG) accumulation in the sensorimotor, limbic, and associative domains of basal ganglia and thalamic nuclei of four groups of nonhuman primates: normal, parkinsonian, parkinsonian chronically treated with L-dopa without exhibiting dyskinesia, and parkinsonian chronically treated with L-dopa and exhibiting overt dyskinesia. Although nondyskinetic animals display a rather normalized metabolic activity, dyskinetic animals are distinguished by significant changes in 2-DG accumulation in limbic- and associative-related structures and not simply in sensorimotor-related ones, suggesting that dyskinesia is linked to a pathological processing of limbic and cognitive information. We propose that these metabolic changes reflect the underlying neural mechanisms of not simply motor dyskinesias but also affective, motivational, and cognitive disorders associated with long-term exposure to L-dopa.
Guigoni
Céline
C
Basal Gang, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 5543, Université Victor Segalen-Bordeaux 2, 33076 Bordeaux Cedex, France.
Li
Qin
Q
Aubert
Incarnation
I
Dovero
Sandra
S
Bioulac
Bernard H
BH
Bloch
Bertrand
B
Crossman
Alan R
AR
Gross
Christian E
CE
Bezard
Erwan
E
D000818:Animals; D001479:Basal Ganglia / Q000737:chemistry / Q000503:physiopathology*; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005917:Globus Pallidus / Q000737:chemistry / Q000503:physiopathology; D007980:Levodopa / Q000627:therapeutic use / Q000633:toxicity*; D008032:Limbic System / Q000737:chemistry / Q000503:physiopathology*; D008252:Macaca fascicularis; D009044:Motor Cortex / Q000737:chemistry / Q000503:physiopathology; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000503:physiopathology; D012686:Septal Nuclei / Q000737:chemistry / Q000503:physiopathology; D013003:Somatosensory Cortex / Q000737:chemistry / Q000503:physiopathology; D013378:Substantia Nigra / Q000737:chemistry / Q000503:physiopathology; D020531:Subthalamic Nucleus / Q000737:chemistry / Q000503:physiopathology
D007980:Levodopa; D003847:Deoxyglucose
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