Role of receptor heterodimers in the development of L-dopa-induced dyskinesias in the 6-hydroxydopamine rat model of Parkinson's disease.
Chronic L-dopa administration is associated with development of dyskinesias. The molecular mechanisms of these side-effects, however, remain elusive. Dopamine (DA) receptors interact with other receptors to form highly organized complexes where their activity is finely tuned by several proteins. The DA D1R forms a heteromeric complex with the NMDA receptor (NMDAR) and this interaction influences the trafficking of both receptors. Using the 6-hydroxydopamine rat model of Parkinson's disease, we report a correlation between the development of L-dopa-induced dyskinesias and changes in synaptic D1R/NMDAR complexes.
Fiorentini
Chiara
C
Division of Pharmacology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Viale Europa 11, Brescia, Italy.
Busi
Chiara
C
Spano
Pierfranco
P
Missale
Cristina
C
D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects*; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000209:etiology* / Q000378:metabolism*; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D008958:Models, Molecular; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology; D021122:Protein Subunits / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D021122:Protein Subunits; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D007980:Levodopa; D016627:Oxidopamine