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

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Author(s)

Abstract

An electrophysiological study was performed to investigate the effects of <I>cis-N</I>-[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 D<SUB>2</SUB>/5-HT<SUB>2</SUB>-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 D<SUB>2</SUB>-receptors, these findings suggest that perospirone acts on the D<SUB>2</SUB>-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, 1997-10-01

    The Japanese Pharmacological Society

References:  25

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008189707
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4326416
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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