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Naloxone antagonizes GABA(A)/benzodiazepine receptor function in rat corticohippocampal synaptoneurosomes.

Journal article
Authors Anders I Svensson
A Berntsson
M Eirefelt
Bo Söderpalm
Published in Journal of neural transmission (Vienna, Austria : 1996)
Volume 107
Issue 3
Pages 261-70
ISSN 0300-9564
Publication year 2000
Published at Institute of Physiology and Pharmacology, Dept of Pharmacology
Pages 261-70
Language en
Links www.ncbi.nlm.nih.gov/entrez/query.f...
Keywords Amobarbital, pharmacology, Animals, Cerebral Cortex, cytology, Chlorine, pharmacokinetics, GABA Modulators, pharmacology, Hippocampus, cytology, Male, Morphine, pharmacology, Naloxone, pharmacology, Naltrexone, pharmacology, Narcotic Antagonists, pharmacology, Narcotics, pharmacology, Neurons, drug effects, physiology, Radioisotopes, diagnostic use, Rats, Rats, Sprague-Dawley, Receptors, GABA-A, antagonists & inhibitors, Synaptosomes, drug effects, gamma-Aminobutyric Acid, pharmacology
Subject categories Pharmacology, Substance Abuse

Abstract

Several lines of behavioral and neurochemical evidence indicate GABA(A)-antagonistic properties of naloxone. Here, the effects of naloxone on rat brain GABA(A)/benzodiazepine receptor function in vitro were investigated. Naloxone, naltrexone and morphine (10-1,000 microM) reduced GABA-induced (10 microM) 36Cl- uptake in corticohippocampal synaptoneurosomes. Furthermore, the concentration-response curve for GABA-induced 36Cl- uptake (GABA 3-100 microM) was shifted to the right both by naloxone and morphine (1,000 microM). Naloxone also reduced the 36Cl- uptake induced by GABA + diazepam (3 microM + 1 microM) but not that induced by amobarbital (500 microM). The naloxone-induced (1,000 microM) reduction of GABA-mediated (10 microM) 36Cl- uptake was reversed by amobarbital (10-1,000 microM) but not by flumazenil (10-1,000 microM) or morphine (0.1-1,000 microM). These results indicate that naloxone, naltrexone and morphine are weak negative modulators of GABA(A)/benzodiazepine receptor function. The naloxone effect most likely does not involve opiate receptors or the benzodiazepine site on GABA(A) receptor complexes.

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