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The Journal of Neuroscience, February 23, 2005, 25(8):2102-2107; doi:10.1523/JNEUROSCI.5059-04.2005

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BRIEF COMMUNICATION
Involvement of Sensorimotor, Limbic, and Associative Basal Ganglia Domains in L-3,4-Dihydroxyphenylalanine-Induced Dyskinesia

Céline Guigoni,¹ Qin Li,³ Incarnation Aubert,² Sandra Dovero,¹ Bernard H. Bioulac,¹ Bertrand Bloch,² Alan R. Crossman,⁴ Christian E. Gross,¹ and Erwan Bezard¹

¹Basal Gang, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 5543, and ²CNRS UMR 5541, Université Victor Segalen-Bordeaux 2, 33076 Bordeaux Cedex, France, ³Laboratory Animal Research Center, China Agricultural University, Beijing 100101, China, and ⁴School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom

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.

Key words: 2-deoxyglucose; globus pallidus pars externalis; subthalamic nucleus; mediodorsal nucleus; nucleus stria terminalis; basal ganglia

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Received July 20, 2004; revised January 12, 2005; accepted January 15, 2005.

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