Naloxone antagonizes GABA(A)/benzodiazepine receptor function in rat corticohippocampal synaptoneurosomes.
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.
Svensson
A I
AI
Institute of Physiology and Pharmacology, Department of Pharmacology, University of Göteborg, Sweden.
Berntsson
A
A
Eirefelt
M
M
Söderpalm
B
B
D000654:Amobarbital / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology; D002713:Chlorine / Q000493:pharmacokinetics; D018757:GABA Modulators / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000166:cytology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011868:Radioisotopes; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018757:GABA Modulators; D058787:GABA-A Receptor Antagonists; D009292:Narcotic Antagonists; D009294:Narcotics; D011868:Radioisotopes; D009270:Naloxone; D002713:Chlorine; D005680:gamma-Aminobutyric Acid; D009271:Naltrexone; D009020:Morphine; D000654:Amobarbital