Animal Models and Drug Screens for Depression: Pragmatism and the Validity Requirement

Abstract

The search for animal models of depressive illness presents a most difficult task even though it may periodically appear that suitably reliable compounds for the treatment of depressive illness are within grasping distance. Research strategies for understanding the etiology, pathogenesis and treatment of depressive disorders remain among the most varied, confused and strenuous pursuits in the neuropharmacology of drug development. Any attempt to produce an animal model must be considered very much a pragmatic effort but this consideration in no way decreases the necessity of continued search: pragmatism has generally provided great benefits for the suffering. Among the many reasons for the failures to obtain completely reliable and valid animal models of depression, one may consider the enormous complexity of the disorder, as for example illustrated by the distinction between bipolar and unipolar illness in affective disorders. Thus, the bipolar disorder is characterized by episodes of both major depression and mania whereas the unipolar disorder is characterized by episodes of major depression. Other types of affective disorders related to depressive illness (as outlined and reviewed in DSM HI) include cyclothymic disorder, involving varying periods of depression and hypomania, dysthymic disorder, a chronic mood disorder less severe than major depression, and, seasonal affective disorders. The existing test models and bioassays simply cannot cope with complexity of this order: one must therefore weight the term ‘animal model’ most stringently before applying it and in most cases make a preferred reference to ‘drug screens’. In spite of these misgivings, the papers by Panksepp.