Animal models as tools to study the pathophysiology of depression

Abstract

The incidence of depressive illness is high worldwide, and the inadequacy of currently available drug treatments contributes to the significant health burden associated with depression. A basic understanding of the underlying disease processes in depression is lacking; therefore, recreating the disease in animal models is not possible. Popular current models of depression creatively merge ethologically valid behavioral assays with the latest technological advances in molecular biology. Within this context, this study aims to evaluate animal models of depression and determine which has the best face, construct, and predictive validity. These models differ in the degree to which they produce features that resemble a depressive-like state, and models that include stress exposure are widely used. Paradigms that employ acute or sub-chronic stress exposure include learned helplessness, the forced swimming test, the tail suspension test, maternal deprivation, chronic mild stress, and sleep deprivation, to name but a few, all of which employ relatively short-term exposure to inescapable or uncontrollable stress and can reliably detect antidepressant drug response.

Antidepressant effects of ketamine and the roles of AMPA glutamate receptors and other mechanisms beyond NMDA receptor antagonism

“…Numerous studies have successfully duplicated the positive effects of ketamine in rodent tests or models of de pression, including the forced swim test (FST; the most commonly used preclinical screen for antidepressant activ ity) and the chronic mild stress paradigm (CMS; the most commonly used preclinical model of depression). 18 A single systemic injection of ketamine at an intraperitoneal dose of 10mg/kg produces a significant reduction in FST immobil ity shortly (30 minutes to 1 hour) after administration, which has been shown to persist for an average of 7 days in both rats and mice. [19][20][21][22] In addition, although rodents ex posed to chronic stress exhibit depressivelike behaviours, including despair/helplessness (as in the FST) and anhedo nia (as in the sucrose preference test [SPT]), ketamine is able to reverse these effects.…”

Experimental Models of Depression: An Overview to Validity and Reliability Criteria

“…Nitekim, deneysel hayvan modelleri ile depresyon gibi çeşitli psikiyatrik hastalıkların belli yönleri, belli seviyelerde ve belli kısıtlılıklarda hayvanlarda taklit edilebilmektedir. [4][5][6][7] Deneysel depresyon modellerinin geçerlilikle-rinin belirlenmesi ve kliniğe uyarlanabilirliklerinin anlaşılması; yapılan çalışmaların kalitesi ve öne sürülen bulguların literatürdeki yeri bakımından büyük önem taşımaktadır. Deney hayvanlarında oluşturulan depresyon modellerinde geçerlilik kavramı, ilk kez 1969 yılında McKinney ve Bunny tarafından ortaya atılmıştır.…”

Modelos animais em psiquiatria: avanços e desafios

“…É um dos modelos mais difundidos e utilizados, tanto pela rapidez e fácil execução do teste como pela reprodutibilidade entre diferentes laboratórios. Apesar disso, existem limitações a este modelo, sendo uma das mais importantes a de que o estado de desamparo aprendido não é sustentado e, além disso, responde agudamente ao uso de antidepressivos, ao contrário do que se observa em pacientes deprimidos, que geralmente melhoram após algumas semanas do uso da medicação (Abelaira et al, 2013). Além disso, faz-se necessário um teste de campo aberto para avaliar a locomoção, para que se detecte falsos positivos nos casos de medicações que aumentem a locomoção, prolongando assim o tempo de tentativa de fuga, assim como os falsos negativos, no caso de medicações sedativas que promovam um menor tempo de tentativa de fuga nos animais.…”