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In addition, drugs that reduce the availability of monoamines cause symptoms of depression. From such observations the monoamine theory of depression and mania was formed: Depression is due to an absolute or relative decrease in monoamines, or a decrease in receptor sensitivity, at certain receptor sites in the brain. Mania is due to an absolute or relative excess of monoamines or an increase in receptor sensitivity at these sites.
Even after years of research, it is still not clear which receptor sites or which monoamines are involved, although noradrenaline, serotonin and dopamine are all implicated. Neither does the theory explain how mania and depression can exist in the same patient.