In vivo evidence of D3 dopamine receptor sensitization in parkinsonian primates and rodents with l-DOPA-induced dyskinesias.
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.
Sánchez-Pernaute
Rosario
R
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
Jenkins
Bruce G
BG
Choi
Ji-Kyung
JK
Iris Chen
Yin-Ching
YC
Isacson
Ole
O
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D015259:Dopamine Agents / Q000494:pharmacology*; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000378:metabolism*; D007980:Levodopa / Q000494:pharmacology; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging; D008297:Male; D020734:Parkinsonian Disorders / Q000150:complications / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D015259:Dopamine Agents; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D007980:Levodopa; C031349:7-hydroxy-2-N,N-dipropylaminotetralin