Effect of apomorphine infusion on dopamine synthesis rate relates to dopaminergic tone

Neuropharmacology. 1998 Aug;37(8):989-95. doi: 10.1016/s0028-3908(98)00085-9.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apomorphine / pharmacology*
  • Dopamine / biosynthesis*
  • Dopamine Agonists / pharmacology*
  • Female
  • Infusions, Intravenous
  • Linear Models
  • Macaca mulatta
  • Tomography, Emission-Computed

Substances

  • Dopamine Agonists
  • Apomorphine
  • Dopamine