The effects of chronic ingestion of corticosterone (8 weeks via the drinking water, 400 micrograms/ml) on spatial memory performance and on monoamine levels in brain areas related to memory were investigated. Corticosterone treatment was associated with a long lasting (5 weeks post treatment) increase in 5-HT levels (44%) in the dentate gyrus of the hippocampus and decrease in 5-HT (50%) and NE (36%) levels in the frontal cortex. No effects were found in CA1, CA3 or in nucleus basalis. Performance of the rats on an 8-arm radial arm maze showed no overall effect of corticosterone treatment on trials to criterion or choice accuracy scores. However, three of the treated rats, who had consumed the most corticosterone during treatment, 12.5 +/- 0.3 mg/day, were impaired relative to all subjects. Thus, these results suggest that hippocampal serotonergic terminals show long lasting effects from corticosterone and may also be an early indicator of deleterious effects of glucocorticoids on hippocampal function. However, since only a small number of corticosterone-treated rats showed behavioral changes, future experiments are necessary to address the possibility that a higher level of corticosterone intake alters spatial memory as well as brain morphology and neurochemistry. Additional studies are also needed to determine whether such changes represent a threshold effect of the steroid or a dose-response function.