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Effect of the acute and chronic administration of the putative atypical antipsychotic drug Y‐931 (8‐fluoro‐12‐ (4‐methylpiperazin‐1‐yl)‐6H‐[1]benzothieno[2,3b][1,5] benzodiazepine maleate) on spontaneously active rat midbrain dopamine neurons: An in vivo electrophysiological study
Author(s) -
Minabe Yoshio,
Hashimoto Kenji,
Shirayama Yukihiko,
Ashby Charles R.
Publication year - 2004
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10280
Subject(s) - benzodiazepine , antipsychotic drug , drug , antipsychotic , pharmacology , medicine , drug administration , administration (probate law) , atypical antipsychotic , schizophrenia (object oriented programming) , psychiatry , receptor , political science , law
This study examined the effect of the p.o. administration of the putative atypical antipsychotic drug Y‐931 (8‐fluoro‐12‐(4‐methylpiperazin‐1‐yl)‐6H‐[1]benzothieno[2,3b][1,5] benzodiazepine maleate) on the activity of spontaneously active dopamine (DA) neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNC) in anesthetized male Sprague‐Dawley rats. This was accomplished using in vivo electrophysiology. The acute p.o. administration of Y‐931 did not significantly alter the number of spontaneously active SNC DA neurons compared to vehicle‐treated animals. A single p.o. administration of 3 and 10 mg/kg of Y‐931 significantly increased and decreased, respectively, the number of spontaneously active VTA DA neurons compared to vehicle‐treated animals. The acute administration of 3 mg/kg of Y‐931 significantly altered the firing pattern parameters for all spontaneously active SNC DA. The 3 and 10 mg/kg doses of Y‐931 significantly increased the degree of bursting and irregular activity of spontaneously active VTA and SNC DA neurons firing in a bursting pattern. The repeated p.o. administration (21 days) of 1, 3, or 10 mg/kg of Y‐931 significantly decreased the number of spontaneously active VTA DA neurons but had no significant effect on SNC DA neurons compared to vehicle‐treated animals. The repeated administration of Y‐931 did not significantly alter the firing pattern of all spontaneously active SNC or VTA DA neurons. Our findings indicate that the acute and chronic administration of Y‐931 significantly alters the activity of midbrain DA neurons in rats and the electrophysiological profile of chronic Y‐931 resembles that of atypical antipsychotic agents. Synapse 51:19–26, 2004. © 2003 Wiley‐Liss, Inc.