Naloxone as a GABA antagonist: Evidence from iontophoretic, receptor binding and convulsant studies

doi:10.1016/0014-2999(78)90369-2

European Journal of Pharmacology

Volume 47, Issue 1, 1 January 1978, Pages 19-27

https://doi.org/10.1016/0014-2999(78)90369-2 Get rights and content

Abstract

From the following three lines of evidence, it is proposed that at least part of the convulsant activity of naloxone is a result of GABA receptor blockade. Firstly, iontophoretic naloxone reversibly antagonized GABA-evoked depression of firing rate in 21 of 27 neurons tested in the rat olfactory tubercle-nucleus accumbens region, without blocking inhibition evoked in the same cells by glycine (15 cells) or morphine (6 cells). Secondly, i.p. naloxone in high doses caused convulsions in mice, and potentiated the convulsant activity of bicuculline, but not that of strychnine. Diazepam, which protected mice against convulsions elicited by bicuculline, but not by strychnine, also protected mice against naloxone. Thirdly, naloxone, morphine, levorphanol and its non-analgesic enantionmer dextrorphan displaced ³H-GABA from GABA receptor sites in homogenates of human cerebellum, all with comparable low potencies (IC₅₀ = 250–400 μM). There was no correlation with affinities at the stereospecific receptor sites that mediate opiate-induced analgesia, since the potent opiates etorphine and diprenorphine were relatively inactive (IC₅₀ > 3 mM. In addition naloxone displaced ³H-GABA from receptor sites in rate forebrain and cerebellum, with similar low potency.

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^∗: Fellow of the Pharmaceutical Manufacturers Association Foundation, Inc., and of the Foundations' Fund for Research in Psychiatry. Present address: Nevrofysiologisk Institutt, University of Oslo, Karl Johans gt. 47, Oslo 1, Norway.

^∗∗: Present address: Department of Human Physiology and Pharmacology, University of Adelaide, Adelaide, S.A. 5001, Australia.

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Naloxone as a GABA antagonist: Evidence from iontophoretic, receptor binding and convulsant studies

Abstract

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Life Sci.

Brain Res.

Electrical activity in the cat olfactory cortex produced by synchronous orthodromic volleys

J. Neurophysiol.

Huntington's Chorea. Post-mortem measurement of glutamic acid decarboxylase, choline acetyltransferase and dopamine in basal ganglia

Brain

Effect of etorphine, morphine and diprenorphine on neurones of the cerebral cortex and spinal cord of the rat

Brit. J. Pharmacol.

Naloxone and related compounds

Actions and interactions of morphine and dopamine on single neurones in the rat caudate nucleus

Brit. J. Pharmacol.

Evidence for naloxone and opiates as GABA antagonists

Brit. J. Pharmacol.

Central nervous system distribution and metabolism of C14-morphine during morphine-induced feline mania

J. Pharmacol. Exptl. Therap.

The depression of spinal inhibition by morphine

Agents Actions

Benzodiazepines and central glycine receptors

Brit. J. Pharmacol.

Lethality of the morphine isomers levorphanol and dextrorphan

Brit. J. Pharmacol.

Central nervous system distribution and metabolism of C¹⁴-morphine during morphine-induced feline mania