Hongjing Yu, Kumatoshi Ishihara, Hiroaki Matsubayashi, Taku Amano and
Masashi Sasa (*)
Department of Pharmacology, Hiroshima University school of Medicine,
Hiroshima 734, Japan
(*) To whom correspondence should be addressed.
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.
Keywords: Electrophysiology, Ventral tegmental area, Methamphetamine,
Perospirone, Dopaminergic D2-receptor