Format

Send to

Choose Destination
Neurobiol Dis. 2007 Aug;27(2):220-7. Epub 2007 May 18.

In vivo evidence of D3 dopamine receptor sensitization in parkinsonian primates and rodents with l-DOPA-induced dyskinesias.

Author information

1
McLean Hospital/Harvard University Udall Parkinson's Disease Research Center of Excellence, McLean Hospital, 115 Mill St., Belmont, MA 02478, USA. rpernaute@hms.harvard.edu

Abstract

A growing body of evidence indicates a role for D(3) receptors in l-DOPA-induced dyskinesias. This involvement could be amenable to non-invasive in vivo analysis using functional neuroimaging. With this goal, we examined the hemodynamic response to the dopamine D(3)-preferring agonist 7-hydroxy-N,N-di-n-propyl-2 aminotetralin (7-OHDPAT) in naïve, parkinsonian and l-DOPA-treated, dyskinetic rodents and primates using pharmacological MRI (phMRI) and relative cerebral blood volume (rCBV) mapping. Administration of 7-OHDPAT induced minor negative changes of rCBV in the basal ganglia in naïve and parkinsonian animals. Remarkably, the hemodynamic response was reversed (increased rCBV) in the striatum of parkinsonian animals rendered dyskinetic by repeated l-DOPA treatment. Such increase in rCBV is consistent with D(1) receptor-like signaling occurring in response to D(3) stimulation, demonstrates a dysregulation of dopamine receptor function in dyskinesia and provides a potentially novel means for the characterization and treatment of l-DOPA-induced dyskinesia in patients.

PMID:
17588764
PMCID:
PMC2674779
DOI:
10.1016/j.nbd.2007.04.016
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center