Role of serotonin neurons in the induction of levodopa- and graft-induced dyskinesias in Parkinson's disease.
Recent studies in animal models of Parkinson's disease (PD) have provided evidence that dopamine released from spared serotonin afferents can act as a trigger of dyskinetic movements induced by repetitive, low doses of levodopa. Serotonin neurons have the capacity to store and release dopamine synthesized from systemically administered levodopa. However, because of the lack of any autoregulatory feedback control, dopamine released from serotonin terminals results in excessive swings in extracellular dopamine levels after peripheral administration of levodopa. Such "dysregulated" release of levodopa-derived dopamine is likely to be responsible for the appearance of the abnormal movements in levodopa-primed animals. This mechanism may also play a role in the development of graft-induced dyskinesias in patients that receive fetal neuron transplants, possibly due to the inclusion of serotonin neurons in the grafted ventral midbrain tissue, which contribute to maintain dopamine receptors of the denervated striatum in a supersensitive state.
Carta
Manolo
M
Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.
Carlsson
Thomas
T
Muñoz
Ana
A
Kirik
Deniz
D
Björklund
Anders
A
D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects*; D004195:Disease Models, Animal; D020820:Dyskinesias / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010300:Parkinson Disease / Q000628:therapy; D012701:Serotonin / Q000378:metabolism*; D019737:Transplants / Q000009:adverse effects*
D000978:Antiparkinson Agents; D012701:Serotonin; D007980:Levodopa