Galanin can be synthesized in several ascending systems including cholinergic forebrain neurons, serotonergic dorsal raphe neurons, and the noradrenergic locus coeruleus system. Recent immunohistochemical studies suggest that of these three systems, the locus coeruleus neurons express the highest levels of galanin and that in cortex and hippocampus galanin peptide can only be detected in the noradrenergic projections. Electrophysiologic studies show that galanin hyperpolarizes both serotonergic dorsal raphe neurons and noradrenergic locus coeruleus neurons at fairly high concentrations (10(6)-10(-7) M). In addition, galanin at low concentrations (10(-9) M) enhances the 5-HT- and noradrenaline-induced hyperpolarization. Consequently, a galanin antagonist could attenuate an inhibitory tone on both dorsal raphe and locus coeruleus neurons and thus perhaps exert antidepressant activity.