Interactions of pharmacological agents which alter biogenic amine metabolism and depression: An analysis of contributing factors within a primate model of depression

Abstract

The observation that the biogenic amine depleting agent, reserpine, could induce severe depression in a small proportion of the patients treated with it has proved to be a seminal finding in what is now a much larger field of research relating the function of brain biogenic amine systems to emotions and behavior. A review of the human reserpine literature suggests, however, that factors other than pharmacologically produced alterations in brain biogenic amine metabolism must have been critical determinants of the eventual mood alterations observed in conjunction with reserpine treatment. While some of these factors, such as previous history of depression, ongoing psychosocial and environmental stress, can be intuitively identified, there are practical as well as ethical problems involved in actually testing the relative contribution of these factors in precipitating human depression and thereby determining their importance in a quantitative fashion. In the present paper we have attempted to examine, in a nonhuman primate model of depression, the degree to which factors such as prior rearing condition, repeated peer separation, and housing environment can interact with the behavioral effects produced by biogenic amine depleting agents. Major emphasis will be placed on studies utilizing alpha-methyl-para-tyrosine, an inhibitor of tyrosine hydroxylase, to ostensively reduce levels of the catecholamine neurotransmitters norepinephrine and dopamine. The results of these studies provide quantitative estimates, in terms of dose-effect relationships, of the degree to which a number of factors can combine to produce despair-like behavior in rhesus monkeys. These data may be of practical importance in evaluating the contribution of similar factors to the precipitation of human depression. Analysis of some of the existing literature relating alterations in behavior to changes in biogenic amine metabolism in animals suggests that there are important differences between rodent and primate species. These differences, when fully established, may indicate that additional research examining the mechanisms whereby modest alterations in biogenic amine metabolism can interact with environmental and social stress is needed.