Cocaine-induced increases in vesicular dopamine uptake: Role of dopamine receptors

Citation
Jm. Brown et al., Cocaine-induced increases in vesicular dopamine uptake: Role of dopamine receptors, J PHARM EXP, 298(3), 2001, pp. 1150-1153
Citations number
22
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
ISSN journal
0022-3565 → ACNP
Volume
298
Issue
3
Year of publication
2001
Pages
1150 - 1153
Database
ISI
SICI code
0022-3565(200109)298:3<1150:CIIVDU>2.0.ZU;2-7
Abstract
The vesicular monoamine transporter-2 is the sole transporter responsible f or sequestration of monoamines, including dopamine (DA), into synaptic vesi cles. Previous studies demonstrate that agents that inhibit DA transporter function, such as cocaine, increase vesicular [H-3]DA uptake and binding of the ligand [H-3]dihydrotetrabenazine ([H-3]DHTBZ), as assessed in vesicles prepared from treated rats. The present studies examine the role of DA rec eptors in these cocaine-induced effects. Results demonstrate that administr ation of the D-2 DA receptor antagonist, eticlopride, but not the D-1 DA re ceptor antagonist, SCH23390, inhibited these cocaine-induced increases. Sim ilar to the effects of cocaine, treatment with the D-2 agonist, quinpirole, increased both vesicular [H-3]DA uptake and [H-3]DHTBZ binding. In contras t, administration of the D-1 agonist, SKF81297, was without effect on vesic ular [H-3]DA uptake or [H-3]DHTBZ binding. Finally, coadministration of qui npirole and cocaine did not further increase vesicular [H-3]DA uptake or [H -3]DHTBZ binding when compared with treatment with either agent alone. Thes e data suggest that cocaine-induced increases in vesicular DA uptake and DH TBZ binding are mediated by a D-2 receptor-mediated pathway. Furthermore, r esults indicate that D-2 receptor activation, per se, is sufficient to incr ease vesicular DA uptake.