Plastic effects of L-DOPA treatment in the basal ganglia and their relevance to the development of dyskinesia.
The development of L-DOPA-induced dyskinesia (LID) is attributed to plastic responses triggered by dopamine (DA) receptor stimulation in the parkinsonian brain. This article reviews studies that have uncovered different levels of maladaptive plasticity in animal models of LID. Rats developing dyskinesia on chronic L-DOPA treatment show abnormal patterns of signaling pathway activation and synaptic plasticity in striatal neurons. In addition, these animals show a gene expression profile indicative of structural cellular plasticity, including pronounced upregulation of genes involved in extracellular matrix remodeling, neurite extension, synaptic vesicle trafficking, and endothelial and cellular proliferation. Structural changes of neurons and microvessels within the basal ganglia are currently being unraveled by detailed morphological analyses. The structural and functional adaptations induced by L-DOPA in the brain can be viewed as an attempt to meet increased metabolic demands and to boost cellular defense mechanisms. These homeostatic responses, however, also predispose to the appearance of dyskinesia and other complications during the course of the treatment.
Cenci
M Angela
MA
Basal Ganglia Pathophysiology Unit, Dept. Experimental Medical Science, Lund University, BMC F11, 221 84 Lund, Sweden. Angela.Cenci_Nilsson@med.lu.se
Ohlin
K Elisabet
KE
Rylander
Daniella
D
D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000494:pharmacology*; D001479:Basal Ganglia / Q000187:drug effects* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000494:pharmacology*; D055806:Microvessels / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects*; D010300:Parkinson Disease / Q000188:drug therapy; D012701:Serotonin / Q000378:metabolism
D000978:Antiparkinson Agents; D019208:Brain-Derived Neurotrophic Factor; D012701:Serotonin; D007980:Levodopa