The effects of propofol, a hydrophobic intravenous anaesthetic, and fentanyl, an opiate analgesic, on extracellular concentrations of gamma-aminobutyric acid (GABA) in the nucleus accumbens of rats were studied using in vivo brain microdialysis. The concentrations of GABA in the microdialysate of the nucleus accumbens reached a stable baseline value approximately 24 h after probe insertion and were not affected over the ensuing 250 min by intravenous injection of vehicle (1.0 ml/kg) or perfusion of tetrodotoxin (2 microM) into the nucleus accumbens via the dialysis membrane. Propofol (2.5 mg/kg and 10.0 mg/kg i.v.) did not significantly affect the accumbens microdialysate concentration of GABA over the 250 min of quantification. Fentanyl (100 microM) infused for 25 min into the nucleus accumbens via the dialysis membrane produced a marked and transient increase in accumbens GABA concentration to a maximum of approximately 1200% at its peak effect that occurred at 25 min after cessation of the fentanyl infusion.