Animal models of major depressive disorder and the implications for drug discovery and development

ABSTRACT

Introduction: Depression is a highly debilitating psychiatric disorder that affects the global population and causes severe disabilities and suicide. Depression pathogenesis remains poorly understood, and the disorder is often treatment-resistant and recurrent, necessitating the development of novel therapies, models and concepts in this field.

Areas covered: Animal models are indispensable for translational biological psychiatry, and markedly advance the study of depression. Novel approaches continuously emerge that may help untangle the disorder heterogeneity and unclear categories of disease classification systems. Some of these approaches include widening the spectrum of model species used for translational research, using a broader range of test paradigms, exploring new pathogenic pathways and biomarkers, and focusing more closely on processes beyond neural cells (e.g. glial, inflammatory and metabolic deficits).

Expert opinion: Dividing the core symptoms into easily translatable, evolutionarily conserved phenotypes is an effective way to reevaluate current depression modeling. Conceptually novel approaches based on the endophenotype paradigm, cross-species trait genetics and ‘domain interplay concept’, as well as using a wider spectrum of model organisms and target systems will enhance experimental modeling of depression and antidepressant drug discovery.

KEYWORDS:

• Depression
• major depressive disorder
• animal modeling
• pathogenesis
• endophenotype

Article highlights

• Depression is a highly debilitating condition that remains poorly understood

• Development of new therapeutic methods and antidepressants is urgently needed in the field.

• Animal models represent a valuable tool to study depression-associated conditions

• Multiple new approaches to study depression are continuously emerging

• Complex endophenotype-driven approaches will enhance drug screening and basic research of major depression

This box summarizes key points contained in the article.

Declaration of interest

AV Kalueff is the current President of the International Stress and Behavior Society (ISBS, www.stress-and-behavior.com), chairing the ISBS Special Panel on experimental and translational depression models (2018) that coordinated this multi-laboratory collaborative study. The Panel also comprised of ISBS Fellows Professors M Koshiba (Japan), C Song (China), T Strekalova (Netherlands) and members Professors MS de Abreu (Brazil), B Leonard (Ireland), MO Parker (UK), BH Harvey (South Africa), L Tian, E Vasar (Estonia) and TG Amstislavskaya (Russia). The authors have no other roles or financial involvement with any organization or entity with a financial interest in, or financial conflict with, the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This research was supported by the ‘5-100’ Russian Excellence Program to T Strekalova. KA Demin is supported by the Russian Foundation for Basic Research (RFBR) grant 18-34-00996 and Special Rector’s Fellowship for SPbU PhD students. L Tan is supported by the Estonian Research Council grant MOBTT77.