Biological and behavioral consequences of alterations in monoamine oxidase activity

Abstract

Monoamine oxidase (MAO) has many intraneuronal regulatory metabolic functions as well as detoxifying properties. Inhibition of the enzyme leads to rapid changes in the cellular concentrations of neurotransmitter amines and in the balance between different amines in neurons. Longer term alterations in MAO activity are accompanied by secondary, adaptational changes in neurotransmitter-related receptors, other enzymes, and additional cell functions in brain and other tissues. In addition, MAO inhibition is accompanied by marked changes in the sensitivity of the organism to some dietary constituents (e.g., tyramine, tryptophan, and other amines and amine precursors) as well as to many drugs (e.g., sympathomimetics, opiates, reserpine, and caffeine). While nearly complete MAO inhibition has been said to be required for direct behavioral changes to occur, partial MAO inhibition (reductions of 25-75 percent in enzyme activity) or selective inhibition of either the MAO-A or MAO-B form of the enzyme-especially after longer term inhibitor administration-lead to readily demonstrable alterations in the sensitivity of both animals and man to a variety of exogenous agents, and are also associated with a number of biological changes, including those involving neuroendocrine, blood pressure, and sleep mechanisms. These changes in cellular mechanisms and physiological functions may provide models for evaluating the significance of moderate (40 percent) mean reductions in platelet MAO activity found in chronic schizophrenic patients and some other psychiatric patient populations. The basic principle underlying these models is that MAO inhibition leads to impaired regulation in many neurotransmitter systems and other cellular functions, yielding consquent deficits in the attenuation of responses to exogenous stimuli and to endogenous psychobiological changes.