Figure 1
From: Dyskinesias after neural transplantation in Parkinson's disease: what do we know and what is next?
Serotonin 1A (5-HT 1A ) agonists interfere with the 'dialog' between striatal dopamine (DA) and 5-HT neurons attenuating graft-induced dyskinesias (GIDs). (a) In healthy individuals or in patients with Parkinson's disease (PD) with successful striatal grafting and no GIDs, there is no dialog between DA and 5-HT neurons. The release of DA (blue dots) is regulated by presynaptic dopamine transporters (DAT) and the release of 5-HT (green dots) by serotonin transporters (SERT). (b) In patients with PD who have GIDs, the graft-derived striatal 5-HT hyperinnervation causes dysregulation in the synaptic levels of DA that lead to dyskinesias. 5-HT neurons can take up DA via SERT and release it as a false transmitter. Also, the excess of 5-HT release can act directly on DA neurons and reverse or alter the capacity of DAT, thus causing greater DA release from the grafted DA terminals. (c) Administration of 5-HT1A agonists (red dots) in patients with PD who have GIDs activate the inhibitory 5-HT autoreceptors, thereby diminishing the false release of DA and the excess release of 5-HT from the 5-HT terminals, leading to restoration of striatal synaptic levels of DA and attenuation of dyskinesias.