Apomorphine-induced changes in synaptic dopamine levels: positron emission tomography evidence for presynaptic inhibition.
The authors developed a novel positron emission tomography method to estimate changes in the synaptic level of dopamine ([DA]) induced by direct dopamine agonists (for example, apomorphine) in patients with Parkinson disease. The method is based on the typical asymmetry of the nigrostriatal lesion that often occurs in Parkinson disease. Using the between-side difference (ipsilateral (I) and contralateral (C) putamen to the more affected body side) of the inverse of the putamen [11C]raclopride binding potential (BP), the authors obtained [equation: see text] at baseline (that is, before apomorphine administration) and [equation: see text] after apomorphine administration (assuming the concentration of apomorphine is equal in both putamina). The between-side difference in the estimated synaptic concentration of dopamine (diff[DA]) should remain constant unless apomorphine affects dopamine release differently between the two sides. The authors found that apomorphine given subcutaneously at doses of 0.03 and 0.06 mg/kg induced significant changes in their estimate of diff[DA] (P < 0.05). Such changes were more pronounced when only patients with a stable response to levodopa were considered (P < 0.01). These findings provide in vivo evidence that direct dopamine agonists can inhibit the release of endogenous dopamine. The authors propose that this effect is mainly mediated by the activation of presynaptic D2/D3 dopamine receptors.
de La Fuente-Fernández
R
R
Neurodegenerative Disorders Center, University of British Columbia, Vancouver, British Columbia, Canada.
Lim
A S
AS
Sossi
V
V
Holden
J E
JE
Calne
D B
DB
Ruth
T J
TJ
Stoessl
A J
AJ
D000978:Antiparkinson Agents / Q000627:therapeutic use; D001058:Apomorphine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D007839:Functional Laterality; D006801:Humans; D008297:Male; D008954:Models, Biological; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy; D017729:Presynaptic Terminals / Q000000981:diagnostic imaging*; D020891:Raclopride / Q000493:pharmacokinetics; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D014055:Tomography, Emission-Computed
D000978:Antiparkinson Agents; D020891:Raclopride; D001058:Apomorphine; D004298:Dopamine