D2 RECEPTORS MAY MODULATE THE FUNCTION OF THE STRIATAL TRANSPORTER FOR DOPAMINE - KINETIC EVIDENCE FROM STUDIES IN-VITRO AND IN-VIVO

Recently it was hypothesized by others that the D2 dopamine receptor c an regulate the uptake of dopamine. However, the evidence in support o f this hypothesis, although compelling, was not based on observations related to direct measures of the kinetic activity of the transporter itself. Here kinetic evidence in support of this hypothesis is shown. The apparent time-resolved initial velocity of the transport of 1.0 mu M dopamine into striatal suspensions, measured using rotating disk ele ctrode voltammetry, was found to increase in the presence of the D2 re ceptor agonist, quinpirole, at 100 nM. This effect was reversed by sul piride. In separate studies it was shown that acute and chronic treatm ents with haloperidol at 0.5 mg/kg, i.p., reduced the reuptake transpo rt of dopamine in vivo following intrastriatal stimulation of its rele ase by K+. Thus, it appears that D2 receptors may influence the functi oning of the striatal transporter for dopamine. These results are cons istent with a model in which presynaptically released dopamine may fee d back onto the function of its transporter to increase the velocity o f the clearance of synaptic dopamine following an action potential, su ggesting the existence of a mechanism, in addition to release and synt hesis modulation, for fine-tuning dopaminergic chemical signaling.