Differential Effects of Antidepressants in Adult and Developing Animals

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DESCRIPTION (provided by applicant): Although there is a wealth of data on the molecular, neurochemical and behavioral effects of antidepressants in adult animals, very little is known about the effects of antidepressants in juvenile animals. This gap in our knowledge is of particular concern. Not only have studies shown that depressed adolescents do not respond to antidepressants in the same fashion as do adults, with youngsters showing a particularly poor or lack of antidepressant response to tricyclic antidepressants, but antidepressants might induce behavioral sequelae (e.g., suicidality) that are more prominent in youngsters. Based upon these observations, we propose to compare and contrast the pharmacologic effects of antidepressants in juvenile and adult animals. We previously have shown that some of the adaptive responses to antidepressants that are found in adult animals do not occur in juvenile/adolescent animals. In contrast, our preliminary data suggest that reduced immobility in the forced swim test, a behavioral test response used to predict the clinical effects of antidepressants, occurs in adolescent animals treated with desipramine, a tricyclic antidepressant, despite the clinical observations that tricyclics do not work well in youngsters for treatment of depression. We propose to compare and contrast juvenile and adult adaptive neuroendocrine and behavioral responses to two classes of antidepressants, tricyclics and selective serotonin re-uptake inhibitors. Relevance: Depression contributes markedly to the burden of disease world-wide. The results of the proposed studies will provide new and important information on the mechanisms of action of antidepressants in relation to changes in behavior and brain chemistry, assist in the interpretation of clinical findings, as well as help to drive future basic and clinical research in depression in both adults and adolescents.