The acute and chronic administration of the 5-HT2B/2C receptor antagonist SB-200646A significantly alters the activity of spontaneously active midbrain dopamine neurons in the rat: An in vivo extracellular single cell study

• Published in: Synapse (New York, N.Y.) N.Y.), 2006-06, Vol.59 (8), p.502-512
• Main Authors: Blackburn, Thomas P., Suzuki, Katsuaki, Ashby Jr, Charles R.
• Format: Article
• Language: English
• Subjects: 5-HT2C receptors; dopamine neurons; electrophysiology; ventral tegmental area
• ISSN: 0887-4476; 1098-2396
• DOI: 10.1002/syn.20263

This study examined the effect of the acute and chronic administration of the 5‐HT2B/2C receptor antagonist N‐(1‐methyl‐5‐indolyl)‐N′‐(3‐pyridyl) urea hydrochloride (SB‐200646A) on the activity of spontaneously active DA cells in the substantia nigra pars compacta (SNC) and ventral tegmental area (VTA) in anesthetized, male Sprague‐Dawley rats. This was accomplished using in vivo extracellular single cell recording. The i.v. administration of 4–16 mg/kg of SB‐200646A significantly increased the firing rate and % events as bursts in spontaneously active VTA DA neurons and significantly increased the % events as burst in SNC DA neurons. The acute i.p. administration of 20 and 40 mg/kg of SB‐200646A significantly increased the number of spontaneously active VTA DA neurons when compared with vehicle‐treated controls. The acute administration of 10 mg/kg of SB‐200646A significantly increased the coefficient of variation in spontaneously active SNC and DA neurons when compared with vehicle‐treated controls. However, the acute i.p. administration of 20 mg/kg of SB‐200646A significantly decreased the degree of bursting of VTA DA neurons. Similary, chronic i.p. administration of 10 mg/kg of SB‐200646 did not significantly alter firing, whereas chronic administration of 20 mg/kg of SB‐200646A or 20 mg/kg of clozapine significantly decreased the number of spontaneously active VTA DA neurons when compared with vehicle‐treated controls. The SB‐200646A‐induced decrease in the number of spontaneously active VTA DA neurons was reversed by the i.v. administration of (+)‐apomorphine or (−)‐baclofen. The chronic i.p. administration of either 10 or 20 mg/kg of SB‐200646A did not significantly alter the firing pattern of spontaneously active SNC DA neurons. However, the chronic administration of 20 mg/kg of SB‐200646A significantly increased the degree of bursting in VTA DA neurons when compared with vehicle. Overall, the acute and chronic administration of SB‐200646A produces in vivo electrophysiological effects, resembling that of atypical antipsychotic drugs. Synapse 59:502–512; 2006. © 2006 Wiley‐Liss, Inc.