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.