Abstract
Neurotransmitter transporters play an important role in maintaining synaptic homeostasis and in the actions of many drugs. Utilizing a technique for measuring the kinetics (synthesis, degradation, and half-life) of the dopamine transporter (DAT) protein in the rat striatum and nucleus accumbens, we have investigated the effects of systemic administration of dopamine receptor agonists and antagonists upon DAT kinetics in these brain regions. In the striatum, the dopamine D1 receptor agonist SKF38393 and the dopamine D1 receptor antagonist SCH23390 were without effect. However, the dopamine D2 receptor agonists R-(−)-propylnorapomorphine hydrochloride (NPA) and quinpirole decreased the half-life of DAT. This effect was blocked by the dopamine D2 antagonist eticlopride, which, by itself, increased the half-life of DAT. In the nucleus accumbens, the agonist SKF38393 increased the DAT half-life, whereas the antagonist SCH23390 decreased the half-life. In contrast to the striatum, NPA and quinpirole increased the DAT half-life, which was blocked by eticlopride and by itself had no effect on DAT kinetics. Cocaine increased the half-life of DAT in both the striatum and the nucleus accumbens. The results of the present study suggest that, through dopamine receptors, dopamine indirectly influences DAT protein turnover in the striatum and in the nucleus accumbens, but in different ways.
Footnotes
-
This research was supported by the National Institutes of Health Grants RR00165, DA00418, DA10732, and DA005935.
- Abbreviations:
- DAT
- dopamine transporter
- DA
- dopamine
- RTI-76
- 3β-(3-p-chlorophenyl) tropan-2β-carboxylic acid p-isothiocyanato-phenylethyl ester hydrochloride
- NPA
- R-(−)-propylnorapomorphine hydrochloride
- i.c.v.
- intracerebroventricular
- ANOVA
- analysis of variance
- PKC
- protein kinase C
- Received November 16, 2000.
- Accepted April 4, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|