RT Journal Article SR Electronic T1 Acute and Chronic Administration of the Selective D3Receptor Antagonist SB-277011-A Alters Activity of Midbrain Dopamine Neurons in Rats: An In Vivo Electrophysiological Study JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1166 OP 1174 VO 294 IS 3 A1 Charles R. Ashby, Jr. A1 Yoshio Minabe A1 Geoff Stemp A1 Jim J. Hagan A1 Derek N. Middlemiss YR 2000 UL http://jpet.aspetjournals.org/content/294/3/1166.abstract AB This study examined the effect of acute and repeated p.o. administration of the selective D3 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 accomplished with the technique of in vivo extracellular single-unit recording. A single administration of either 3 or 10 mg/kg SB-277011-A produced a significant increase in the number of spontaneously active substantia nigra pars compacta (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 significantly greater alteration in the firing pattern of spontaneously active A10 DA neurons, particularly at the 3- and 10-mg/kg doses, compared with vehicle-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 A9 or A10 DA neurons. The repeated p.o. administration of 1, 3, or 10 mg/kg SB-277011-A once a day for 21 days produced a significant decrease in the number of spontaneously active A10 DA neurons. The repeated administration of SB-277011-A produced a greater effect on the firing pattern of spontaneously active A10 DA neurons, particularly at the 3-mg/kg dose, compared with A9 DA neurons. Overall, our results indicate that SB-277011-A alters the activity of midbrain DA neurons in rats. The American Society for Pharmacology and Experimental Therapeutics