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.
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 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.
Ashby
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CR
Department of Pharmaceutical Health Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, NY 11439, USA. Crashby@ix.netcom.com
Minabe
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Stemp
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Hagan
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Middlemiss
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D000200:Action Potentials; D000284:Administration, Oral; D000818:Animals; D002452:Cell Count; D004285:Dogs; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000008:administration & dosage / Q000187:drug effects*; D050637:Receptors, Dopamine D3; D013378:Substantia Nigra / Q000166:cytology / Q000502:physiology; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000502:physiology; D044005:Tetrahydroisoquinolines
D018492:Dopamine Antagonists; C493595:Drd3 protein, rat; D009570:Nitriles; D011804:Quinolines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C409982:SB 277011; D044005:Tetrahydroisoquinolines; D006220:Haloperidol