THE effects of intracerebral perfusion of the nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1) and the nitric oxide synthase inhibitor N-nitroarginine (NARC) on the extracellular concentrations of glutamate (GLU) and gamma-aminobutyric acid (GABA) in striatum and CA1 area of the hippocampus were studied. Continuous push-pull perfusions at a flow rate of 20 mu l min(-1) were performed in the conscious rat. SIN-1 (100, 200, and 400 mu M) and NARC (100 mu M) were perfused over 20 min. In both striatum and CA1 SIN-1 increased extracellular concentrations of GLU (maximal increase 150% and 197% of baseline, respectively) and GABA (maximal increase 202% and 204% of baseline, respectively). NARC had no effects on extracellular levels of GLU and GABA in either area, These results are consistent with the hypothesis that NO acts as a modulator of GLU and GABA release in both striatum and hippocampus. This study is the first to report the potentiation of GLU and GABA release by NO in CA1 area of the hippocampus in the conscious rat.