Naloxone antagonizes GABA_A/benzodiazepine receptor function in rat corticohippocampal synaptoneurosomes

Summary.

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 μM) reduced GABA-induced (10 μM) ³⁶Cl⁻ uptake in corticohippocampal synaptoneurosomes. Furthermore, the concentration-response curve for GABA-induced ³⁶Cl⁻ uptake (GABA 3–100 μM) was shifted to the right both by naloxone and morphine (1,000 μM). Naloxone also reduced the ³⁶Cl⁻ uptake induced by GABA + diazepam (3 μM + 1 μM) but not that induced by amobarbital (500 μM). The naloxone-induced (1,000 μM) reduction of GABA-mediated (10 μM) ³⁶Cl⁻ uptake was reversed by amobarbital (10–1,000 μM) but not by flumazenil (10–1,000 μM) or morphine (0.1–1,000 μM). 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.