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An immnosuppressive drug, cyclosporine-A acts like anti-depressant for rats under unpredictable chronic stress.

Rats were subjected to unpredictable chronic stress (UCS), which was composed of 3 cycles of 7 kinds of stress for 21 days. Rats given UCS exhibited a depressive state in behavioral tests such as emergence tests and forced swim tests. Administration of cyclosporine-A (CsA), an immunosuppressive drug, gave rise to antidepressant effect in rats under the UCS, but not in stress-free rats. In other words, CsA shortened both the latency time in emergence tests and the immobility time in forced swim tests in rats given UCS. Analysis of brain tissue by HPLC revealed that CsA caused a significant increase in NE, 5-HT and 5-HIAA levels in the cortex of UCS treated rats, but treatment with either UCS or CsA alone resulted in the opposite effect. Comparing the data of monoamines and their metabolites in the brain, cascades may be different between CsA and imipramine, although both of them showed antidepressive effect in behavioral tests.