Table 1. Serotonin and Graft-induced Dyskinesias (GID).

Striatal 5HT fibers, derived from brainstem host projections and/or donor graft tissue, have been postulated to play a role in GID. Evidence supporting or negating this hypothesis is presented in this table. While there is a great deal of data to suggest that following levodopa administration there is non-regulated DA overflow produced from the striatal serotonergic hyperinnervation within the parkinsonian striatum that causes typical LID behavior in non-grafted subjects, data for the role for 5HT in GID is less certain. However, if we are to accept that 5HT neurons are a causative factor in off-time GID in patients, the question that needs to be considered is: “When the patient is off levodopa, what is the source of excess DA production from serotonin neurons?” Abbreviations: positron emission tomography, PET; single photon emission computed tomography, SPECT; 11C-labeled 3-amino-4-(2-dimethylaminomethylphenylsulfanyl) benzonitrile, 11C-DASB; ventral mesencephalon, VM.

Evidence Supporting a Role for 5HT neurons	Citation	Evidence Against a Role for 5HT neurons	Citation
PET and SPECT evidence shows elevated 5HT/ DA transporter ratio in one PD patient that developed GID; the 5-HT1A agonist/ DA antagonist molecule, given at small, repeated doses suppressed this behavior	[90]	In a rat model, 5-HT cells within a graft were shown to be neither detrimental nor beneficial for functional effects of DA-rich transplants; however, in absence of sufficient numbers of DA neurons, transplanted 5-HT neurons were able to induce dyskinetic behaviors following levodopa (i.e.: LIDs)	[123]
11C-DASB PET imaging of sertonergic innervation shows evidence of excessive serotonergic innervation in the grafted striatum of two patients that exhibited major motor recovery and later developed GID; the 5-HT1A agonist/ DA antagonist molecule, give at small, repeated doses suppressed this behavior	[91]	Evidence demonstrates that in each of 5 PD patients grafted with human fetal VM tissue there were abundant serotonin neurons but that none of them were observed to have GID	[124,125]
		In a rat model, transplant-induced AIMs noted following amphetamine administration were seen to primarily depend on a pharmacological activation of dopamine receptors; and serotonin neurons within either the grafts or the host brain played a negligible role	[24]