Levodopa and pramipexole effects on presynaptic dopamine PET markers and estimated dopamine release.
OBJECTIVE
Levodopa and dopamine (DA) agonist therapy are two common treatments for Parkinson's disease (PD). There is controversy about the effects of these treatments on disease progression and imaging markers. Here we used multi-tracer positron emission tomography imaging and a unilateral 6-hydroxydopamine (6-OHDA) rat model of PD to evaluate in vivo the effects of chronic levodopa and pramipexole treatments on measurements of vesicular monoamine transporter type 2 (VMAT2), dopamine transporter (DAT) levels, and on levodopa-induced changes in synaptic DA levels [Δ(DA)].


METHODS
Twenty-three unilaterally 6-OHDA lesioned rats underwent an 11C-dihydrotetrabenazine (DTBZ, VMAT2 marker), an 11C-methylphenidate (MP, DAT marker), and a double 11C-raclopride (RAC, D2-type receptor marker) scan. They were assigned to three treatment groups: saline (N=7), pramipexole (N=8), and levodopa (N=8). After 4 weeks of treatment, imaging was repeated.


RESULTS
Results showed (1) a significant treatment effect on DTBZ, with pramipexole decreasing DTBZ binding compared to levodopa, (2) significant side and treatment-striatal side interaction effects for MP, indicating that levodopa tends to decrease MP binding compared to pramipexole, and (3) no treatment effect on Δ(DA).


CONCLUSIONS
These data indicate that while chronic dopaminergic pharmacological treatment affects DTBZ and MP binding, it does not affect levodopa-induced changes in synaptic DA level.
Sossi
Vesna
V
University of British Columbia, Vancouver, Canada. vesna@physics.ubc.ca
Dinelle
Katherine
K
Schulzer
Michael
M
Mak
Edwin
E
Doudet
Doris J
DJ
de la Fuente-Fernández
Raúl
R
D000818:Animals; D052160:Benzothiazoles / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000627:therapeutic use; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D020734:Parkinsonian Disorders / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D000077487:Pramipexole; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D052160:Benzothiazoles; D015415:Biomarkers; D018491:Dopamine Agonists; D007980:Levodopa; D000077487:Pramipexole; D004298:Dopamine