Acute and chronic effects of pentobarbital in relation to postsynaptic GABA receptors: A study with muscimol

S. P. Sivam, Toshitaka Nabeshima, I. K. Ho

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Muscimol, a GABA agonist, enhanced pentobarbital sleeping time in a dose‐dependent manner. The GABA antagonists such as bicuculline and picrotoxin, and the CNS stimulant such as pentylenetetrazol, inhibited pentobarbital sleeping time; however, all except picrotoxin produced less than 35% maximum inhibition. Picrotoxin, an agent which blocks the chloride ionophore of GABA‐receptor complex, exhibited a parallel dose‐response curve with respect to muscimol. Chronic administration of pentobarbital by pellet implantation induced tolerance as evidenced by decreased sleeping time; the tolerance receded gradually upon abrupt withdrawal. Muscimol enhanced pentobarbital sleeping time both in tolerant and withdrawal mice. Na+‐independent GABA‐receptor binding, using [3H]muscimol as a ligand, was increased after acute and chronic pentobarbital administration; withdrawal of the pentobarbital reversed the increase in receptor population. None of the treatments altered the affinity of [3H]muscimol binding. These results support the contention that pentobarbital (a) directly acts on the postsynaptic chloride ionophore and (b) augments GABA‐mediated postsynaptic effects. The functional significance of the increase in GABA receptor population after pentobarbital treatment is unclear.

Original languageEnglish
Pages (from-to)37-47
Number of pages11
JournalJournal of Neuroscience Research
Volume7
Issue number1
DOIs
Publication statusPublished - 01-01-1982

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Muscimol
Pentobarbital
GABA-A Receptors
Picrotoxin
Ionophores
Chlorides
GABA Antagonists
GABA Agonists
Pentylenetetrazole
GABA Receptors
Bicuculline
Population
Ligands

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

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title = "Acute and chronic effects of pentobarbital in relation to postsynaptic GABA receptors: A study with muscimol",
abstract = "Muscimol, a GABA agonist, enhanced pentobarbital sleeping time in a dose‐dependent manner. The GABA antagonists such as bicuculline and picrotoxin, and the CNS stimulant such as pentylenetetrazol, inhibited pentobarbital sleeping time; however, all except picrotoxin produced less than 35{\%} maximum inhibition. Picrotoxin, an agent which blocks the chloride ionophore of GABA‐receptor complex, exhibited a parallel dose‐response curve with respect to muscimol. Chronic administration of pentobarbital by pellet implantation induced tolerance as evidenced by decreased sleeping time; the tolerance receded gradually upon abrupt withdrawal. Muscimol enhanced pentobarbital sleeping time both in tolerant and withdrawal mice. Na+‐independent GABA‐receptor binding, using [3H]muscimol as a ligand, was increased after acute and chronic pentobarbital administration; withdrawal of the pentobarbital reversed the increase in receptor population. None of the treatments altered the affinity of [3H]muscimol binding. These results support the contention that pentobarbital (a) directly acts on the postsynaptic chloride ionophore and (b) augments GABA‐mediated postsynaptic effects. The functional significance of the increase in GABA receptor population after pentobarbital treatment is unclear.",
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Acute and chronic effects of pentobarbital in relation to postsynaptic GABA receptors : A study with muscimol. / Sivam, S. P.; Nabeshima, Toshitaka; Ho, I. K.

In: Journal of Neuroscience Research, Vol. 7, No. 1, 01.01.1982, p. 37-47.

Research output: Contribution to journalArticle

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