Basal serotonin (5-HT) release, measured in the presence of imipramine, was significantly reduced in slices of hippocampus, n. accumbens and frontal cortex from rats subjected to forced swim test and chronic isolation. Only in the hippocampus, in the two animal models of depression, K-stimulated release was increased. In the hippocampus and frontal cortex, but not in n. accumbens, tissue content of 5-HT was reduced. This constitutes the first direct demonstration of a decreased tonic release of serotonin from different nuclei during depression. The results also suggest a nuclei specific, facilitator, presynaptic regulation of 5-HT release.