Effect of apomorphine infusion on dopamine synthesis rate relates to dopaminergic tone.
The effects of apomorphine on the striatal L-[11C]DOPA influx rate was examined in anaesthetized Rhesus monkeys using positron emission tomography (PET). In comparison with baseline conditions, the addition of a continuous infusion of apomorphine produced decreases in the striatal L-[11C]DOPA influx rate in all the monkeys examined. The effect of apomorphine infusion also showed a dose-dependent trend. In individual monkeys, the magnitude of the effect showed a baseline dopaminergic tone-dependency; that is, the effect of apomorphine was most pronounced in monkeys with high baseline influx rates, and in monkeys with lower baseline values apomorphine induced a weaker effect. Studies of radiolabeled tracer and radiolabeled metabolites formed in plasma confirmed that apomorphine infusion did not induce any change in the peripheral elimination or metabolite formation of L-[11C]DOPA. The decreased striatal L-[11C]DOPA influx rate induced by apomorphine was interpreted as an agonist effect on dopamine autoreceptors regulating the dopamine synthesis rate. The observation of a baseline dopaminergic tone-dependent effect is in agreement with earlier results showing this influence on the striatal influx rate as measured with the tracer L-[11C]DOPA. A priori, it can be established that L-[11C]DOPA and PET provide a method not only to study the structural integrity of the presynaptic dopaminergic system but also to study the homeostasis-regulating mechanisms of this neurotransmitter system in vivo. The ability to measure condition-dependent effects in individuals should be of great importance in determining specific pathophysiological mechanisms underlying degenerative and functional disorders affecting the dopaminergic system.
Torstenson
R
R
Uppsala University PET Centre, University Hospital, Uppsala University, Sweden.
Hartvig
P
P
Långström
B
B
Bastami
S
S
Antoni
G
G
Tedroff
J
J
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D004298:Dopamine / Q000096:biosynthesis*; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D007262:Infusions, Intravenous; D016014:Linear Models; D008253:Macaca mulatta; D014055:Tomography, Emission-Computed
D018491:Dopamine Agonists; D001058:Apomorphine; D004298:Dopamine