Dopamine D1 and D2 receptors influence dopamine transporter synthesis and degradation in the rat

Neurotransmitter transporters play an important role in maintaining synapti c homeostasis and in the actions of many drugs. Utilizing a technique for m easuring the kinetics (synthesis, degradation, and half-life) of the dopami ne transporter (DAT) protein in the rat striatum and nucleus accumbens, we have investigated the effects of systemic administration of dopamine recept or agonists and antagonists upon DAT kinetics in these brain regions. In th e striatum, the dopamine D1 receptor agonist SKF38393 and the dopamine D1 r eceptor antagonist SCH23390 were without effect. However, the dopamine D2 r eceptor agonists R-(-)-propylnorapomorphine hydrochloride (NPA) and quinpir ole decreased the half-life of DAT. This effect was blocked by the dopamine D2 antagonist eticlopride, which, by itself, increased the half-life of DA T. In the nucleus accumbens, the agonist SKF38393 increased the DAT half-li fe, whereas the antagonist SCH23390 decreased the half-life, In contrast to the striatum, NPA and quinpirole increased the DAT half-life, which was bl ocked by eticlopride and by itself had no effect on DAT kinetics, Cocaine i ncreased the half-life of DAT in both the striatum and the nucleus accumben s. The results of the present study suggest that, through dopamine receptor s, dopamine indirectly influences DAT protein turnover in the striatum and in the nucleus accumbens, but in different ways.