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
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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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