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

Several lines of behavioral and neurochemical evidence indicate GABA(A)-ant agonistic properties of naloxone. Here, the effects of naloxone on rat brai n GABA(A)/benzodiazepine receptor function in vitro were investigated. Nalo xone, naltrexone and morphine (10-1,000 mu M) reduced GABA-induced (10 mu M ) Cl-36(-) uptake in corticohippocampal synaptoneurosomes. Furthermore, the concentration-response curve for GABA-induced Cl-36(-) Up take (GABA 3-100 mu M) was shifted to the right both by naloxone and morphine (1,000 mu M). Naloxone also reduced the Cl-36(-) uptake induced by GABA + diazepam (3 mu M + 1 mu M) but not that induced by amobarbital (500 mu M). The naloxone-i nduced (1,000 mu M) reduction of GABA-mediated (10 mu M) Cl-36(-) uptake wa s reversed by amobarbital (10-1,000 mu M) but not by flumazenil (10-1,000 m u M) or morphine (0.1-1,000 mu M). These results indicate that naloxone, na ltrexone and morphine are weak negative modulators of GABA(A)/benzodiazepin e receptor function. The naloxone effect most likely does not involve opiat e receptors or the benzodiazepine site on GABA(A) receptor complexes.