This study investigates the hypothesis that serotonin mediates certain nicotine effects, such as mood improvement and the suppression of the ponto-geniculo-occipital spikes of rapid eye movement sleep. The influence of nicotine (10-300 microM) on the firing rate of dorsal raphe neurons and on serotonin release was therefore, studied in rat midbrain slices. Nicotine increased the firing rate, 10-90%, in 67.5% recorded neurons and decreased it, 8-100%, in the remaining 32.5%. Serotonin release increased 2-7 times after nicotine administration, regardless of firing frequency, but the absolute value of serotonin release was 3 times higher during the decreases than during the increases in firing rate. Mecamylamine (1-20 microM) transiently stimulated the dorsal raphe neurons and competitively antagonized the nicotine-induced serotonin release. The results support the working hypothesis and additionally show that mecamylamine also stimulates dorsal raphe neurons.