Effects of Perospirone, a Novel Antipsychotic Agent, on the Dopaminergic Neurons in the Rat Ventral Tegmental Area.

• Yu Hongjing

  Department of Pharmacology, Hiroshima University School of Medicine

• Ishihara Kumatoshi

  Department of Pharmacology, Hiroshima University School of Medicine

• Matsubayashi Hiroaki

  Department of Pharmacology, Hiroshima University School of Medicine

• Amano Taku

  Department of Pharmacology, Hiroshima University School of Medicine

• Sasa Masashi

  Department of Pharmacology, Hiroshima University School of Medicine

Bibliographic Information

Other Title

• Effects of Perospirone a Novel Antipsyc

Abstract

An electrophysiological study was performed to investigate the effects of cis-N-[4-[4-(1, 2-benz-isozole-3-yl)-1-piperazinyl]butyl]cyclohexane-1, 2-dicarboximide hydrochloride (perospirone), a novel antipsychotic agent with high affinities for D₂/5-HT₂-receptors, on the dopaminergic (DA) neurons in the ventral tegmental area (VTA) using chloral hydrate-anesthetized rats. DA neurons and non-DA neurons in VTA were identified according to the configurations of their action potentials and firing rates. Spontaneous firing of DA neurons was dose-dependently decreased by i.v. injection of methamphetamine (MAP). Most non-DA neurons were unaffected by MAP up to 2 mg/kg, but the firing was increased with MAP in 2 of 7 neurons. Perospirone injected intravenously reversed the MAP-induced decrease in spontaneous firing of DA neurons in a dose-dependent manner. In addition, i.v. injection of perospirone also inhibited the MAP-induced increase in firing of the 2 non-DA neurons. Similarly, inhibition of spontaneous firing in DA neurons by microiontophoretically applied DA was antagonized during iontophoretic application of perospirone. However, the firing of non-DA neurons, which were insensitive to DA, was not affected by iontophoretically applied perospirone. Since the DA neurons are inhibited by DA via D₂-receptors, these findings suggest that perospirone acts on the D₂-receptors to antagonize the dopaminergic inhibition of DA neurons in VTA.

Journal

• The Japanese Journal of Pharmacology

  The Japanese Journal of Pharmacology 75 (2), 179-185, 1997

  The Japanese Pharmacological Society

Keywords

• Electrophysiology
• Ventral tegmental area
• Methamphetamine
• Perospirone
• Dopaminergic D<SUB>2</SUB>-receptor

Details

• CRID: 1390001204285283712
• NII Article ID: 10008189707
• NII Book ID: AA00691188
• DOI: 10.1254/jjp.75.179
• COI: 1:CAS:528:DyaK2sXntVKmurs%3D
• ISSN: 13473506
• ISSN: 00215198
• NDL BIB ID: 4326416
• PubMed: 9414033
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I4326416
• Web Site: https://search.jamas.or.jp/link/ui/1998151763
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• Abstract License Flag: Disallowed