Acute and chronic administration of the selective D-3 receptor antagonist SB-277011-A alters activity of midbrain dopamine neurons in rats: An in vivo electrophysiological study

Citation
Cr. Ashby et al., Acute and chronic administration of the selective D-3 receptor antagonist SB-277011-A alters activity of midbrain dopamine neurons in rats: An in vivo electrophysiological study, J PHARM EXP, 294(3), 2000, pp. 1166-1174
Citations number
42
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
ISSN journal
0022-3565 → ACNP
Volume
294
Issue
3
Year of publication
2000
Pages
1166 - 1174
Database
ISI
SICI code
0022-3565(200009)294:3<1166:AACAOT>2.0.ZU;2-Q
Abstract
This study examined the effect of acute and repeated p.o. administration of the selective D-3 receptor antagonist SmithKline Beecham (SB)-277011-A (1, 3, or 10 mg/kg) on the activity of spontaneously active midbrain dopamine (DA) neurons in anesthetized, male Sprague-Dawley rats. This was accomplish ed with the technique of in vivo extracellular single-unit recording. A sin gle administration of either 3 or 10 mg/kg SB-277011-A produced a significa nt increase in the number df spontaneously active substantia nigra pars com pacta (or A9) DA neurons compared with vehicle-treated (2% methylcellulose) animals. The 10-mg/kg dose of SB-277011-A produced a significant increase in the number of spontaneously active A10 DA neurons compared with vehicle- treated animals. The acute administration of SB-277011-A produced a signifi cantly greater alteration in the firing pattern of spontaneously active A10 DA neurons, particularly at the 3- and 10-mg/kg doses, compared with vehic le-treated animals. The i.v. administration of SB-277011-A (0.01-1.28 mg/kg ) did not significantly alter the firing rate or firing pattern of either A 9 or A10 DA neurons. The repeated p.o. administration of 1,3, or 10 mg/kg S B-277011-A once a day for 21 days produced a significant decrease in the nu mber of spontaneously active A10 DA neurons. The repeated administration of SB-277011-A produced a greater effect on the firing pattern of spontaneous ly active A10 DA neurons, particularly at the 3-mg/kg dose, compared with A 9 DA neurons. Overall, our results indicate that SB-277011-A alters the act ivity of midbrain DA neurons in rats.