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Research ArticleNEUROPHARMACOLOGY

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

Charles R. Ashby Jr., Yoshio Minabe, Geoff Stemp, Jim J. Hagan and Derek N. Middlemiss
Journal of Pharmacology and Experimental Therapeutics September 2000, 294 (3) 1166-1174;
Charles R. Ashby Jr.
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Yoshio Minabe
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Geoff Stemp
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Jim J. Hagan
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Derek N. Middlemiss
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Abstract

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.

Footnotes

  • Send reprint requests to: Dr. Charles R. Ashby, Jr., Department of Pharmaceutical Health Sciences, College of Pharmacy and Allied Health Professions, St. John's University, 8000 Utopia Pkwy., Jamaica, NY 11439. E-mail: Crashby{at}ix.netcom.com

  • Abbreviations:
    DA
    dopamine
    SB
    SmithKline Beecham
    VTA
    ventral tegmental area
    SNC
    substantia nigra pars compacta
    • Received February 18, 2000.
    • Accepted April 13, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 294 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 294, Issue 3
1 Sep 2000
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Research ArticleNEUROPHARMACOLOGY

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

Charles R. Ashby, Yoshio Minabe, Geoff Stemp, Jim J. Hagan and Derek N. Middlemiss
Journal of Pharmacology and Experimental Therapeutics September 1, 2000, 294 (3) 1166-1174;

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Research ArticleNEUROPHARMACOLOGY

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

Charles R. Ashby, Yoshio Minabe, Geoff Stemp, Jim J. Hagan and Derek N. Middlemiss
Journal of Pharmacology and Experimental Therapeutics September 1, 2000, 294 (3) 1166-1174;
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