Modulation of the decrease in the seizure threshold of pentylenetetrazole in diazepam-withdrawn mice by the neurosteroid 5α-pregnan-3α,21-diol-20-one (alloTHDOC)

Tsuda Makoto, Tsutomu Suzuki, Miwa Misawa

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19 Citations (Scopus)

Abstract

The effect of the neurosteroid 5α-pregnan-3α,21-diol-20-one (alloTHDOC) on pentylenetetrazole (PTZ)-induced diazepam-withdrawal seizure was examined in mice. The threshold for PTZ-induced seizure was markedly decreased by discontinuation of chronic diazepam treatment. The decrease in the seizure threshold of PTZ during diazepam withdrawal was significantly attenuated by pretreatment with alloTHDOC (10 and 20 μg/mouse, i.c.v.), which did not affect the seizure threshold of PTZ in chronically vehicle-treated mice. However, the loss of the righting reflex (LRR) induced by other GABA(A) receptor activators (pentobarbital and propofol) did not differ between control and diazepam-withdrawn mice. These findings provide the first demonstration that alloTHDOC may be able to suppress diazepam withdrawal signs, and that the sensitivity to the pharmacological effect of alloTHDOC via GABA(A) receptor may be enhanced in diazepam-withdrawn mice.

Original languageEnglish
Pages (from-to)455-460
Number of pages6
JournalAddiction Biology
Volume2
Issue number4
DOIs
Publication statusPublished - 1997
Externally publishedYes

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Pentylenetetrazole
Diazepam
Neurotransmitter Agents
Seizures
GABA-A Receptors
Righting Reflex
Propofol
Pentobarbital
Pharmacology

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)

Cite this

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title = "Modulation of the decrease in the seizure threshold of pentylenetetrazole in diazepam-withdrawn mice by the neurosteroid 5α-pregnan-3α,21-diol-20-one (alloTHDOC)",
abstract = "The effect of the neurosteroid 5α-pregnan-3α,21-diol-20-one (alloTHDOC) on pentylenetetrazole (PTZ)-induced diazepam-withdrawal seizure was examined in mice. The threshold for PTZ-induced seizure was markedly decreased by discontinuation of chronic diazepam treatment. The decrease in the seizure threshold of PTZ during diazepam withdrawal was significantly attenuated by pretreatment with alloTHDOC (10 and 20 μg/mouse, i.c.v.), which did not affect the seizure threshold of PTZ in chronically vehicle-treated mice. However, the loss of the righting reflex (LRR) induced by other GABA(A) receptor activators (pentobarbital and propofol) did not differ between control and diazepam-withdrawn mice. These findings provide the first demonstration that alloTHDOC may be able to suppress diazepam withdrawal signs, and that the sensitivity to the pharmacological effect of alloTHDOC via GABA(A) receptor may be enhanced in diazepam-withdrawn mice.",
author = "Tsuda Makoto and Tsutomu Suzuki and Miwa Misawa",
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T1 - Modulation of the decrease in the seizure threshold of pentylenetetrazole in diazepam-withdrawn mice by the neurosteroid 5α-pregnan-3α,21-diol-20-one (alloTHDOC)

AU - Makoto, Tsuda

AU - Suzuki, Tsutomu

AU - Misawa, Miwa

PY - 1997

Y1 - 1997

N2 - The effect of the neurosteroid 5α-pregnan-3α,21-diol-20-one (alloTHDOC) on pentylenetetrazole (PTZ)-induced diazepam-withdrawal seizure was examined in mice. The threshold for PTZ-induced seizure was markedly decreased by discontinuation of chronic diazepam treatment. The decrease in the seizure threshold of PTZ during diazepam withdrawal was significantly attenuated by pretreatment with alloTHDOC (10 and 20 μg/mouse, i.c.v.), which did not affect the seizure threshold of PTZ in chronically vehicle-treated mice. However, the loss of the righting reflex (LRR) induced by other GABA(A) receptor activators (pentobarbital and propofol) did not differ between control and diazepam-withdrawn mice. These findings provide the first demonstration that alloTHDOC may be able to suppress diazepam withdrawal signs, and that the sensitivity to the pharmacological effect of alloTHDOC via GABA(A) receptor may be enhanced in diazepam-withdrawn mice.

AB - The effect of the neurosteroid 5α-pregnan-3α,21-diol-20-one (alloTHDOC) on pentylenetetrazole (PTZ)-induced diazepam-withdrawal seizure was examined in mice. The threshold for PTZ-induced seizure was markedly decreased by discontinuation of chronic diazepam treatment. The decrease in the seizure threshold of PTZ during diazepam withdrawal was significantly attenuated by pretreatment with alloTHDOC (10 and 20 μg/mouse, i.c.v.), which did not affect the seizure threshold of PTZ in chronically vehicle-treated mice. However, the loss of the righting reflex (LRR) induced by other GABA(A) receptor activators (pentobarbital and propofol) did not differ between control and diazepam-withdrawn mice. These findings provide the first demonstration that alloTHDOC may be able to suppress diazepam withdrawal signs, and that the sensitivity to the pharmacological effect of alloTHDOC via GABA(A) receptor may be enhanced in diazepam-withdrawn mice.

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