The age of anxiety: role of animal models of anxiolytic action in drug discovery

Abstract

Anxiety disorders are common, serious and a growing health problem worldwide. However, the causative factors, aetiology and underlying mechanisms of anxiety disorders, as for most psychiatric disorders, remain relatively poorly understood. Animal models are an important aid in giving insight into the aetiology, neurobiology and, ultimately, the therapy of human anxiety disorders. The approach, however, is challenged with a number of complexities. In particular, the heterogeneous nature of anxiety disorders in humans coupled with the associated multifaceted and descriptive diagnostic criteria, creates challenges in both animal modelling and in clinical research. In this paper, we describe some of the more widely used approaches for assessing the anxiolytic activity of known and potential therapeutic agents. These include ethological, conflict-based, hyponeophagia, vocalization-based, physiological and cognitive-based paradigms. Developments in the characterization of translational models are also summarized, as are the challenges facing researchers in their drug discovery efforts in developing new anxiolytic drugs, not least the ever-shifting clinical conceptualization of anxiety disorders. In conclusion, to date, although animal models of anxiety have relatively good validity, anxiolytic drugs with novel mechanisms have been slow to emerge. It is clear that a better alignment of the interactions between basic and clinical scientists is needed if this is to change.

Sex differences in animal models of psychiatric disorders

“…Several experimental models using rodents have been developed in order to study the neurobiology of fear and anxiety, as well as the pharmacology of anxiolytics (Cryan and Sweeney, 2011). Some of these tests induce a conflict between the rodent's drive to explore for potential rewards and its instinct of avoiding potentially dangerous situations, such as illuminated or exposed spaces.…”

Animal models of anxiety disorders and stress

“…34 In 1988, Bodnoff et al 35 validated the novelty suppressed feeding (NSF) test. In this model, animals deprived of food for 24 hours are exposed to a transparent box consisting of a sawdust-covered floor, a central platform holding a single pellet of chow, and focused lighting.…”

Modelos animais em psiquiatria: avanços e desafios

“…No caso dos modelos animais de ansiedade, temos três categorias nas quais estes podem ser classificados, que são os testes etológicos (ou não condicionados), testes de conflito e testes cognitivos baseados ou de condicionamento clássico (Cryan & Sweeney, 2011).…”

“…Mesmo sendo um teste que controle alguns potenciais confundidores, como hiperlocomoção, este modelo é muito sensível a outras alterações como condições do ambiente (luz, barulhos e odores), assim como a diferentes raças de roedores (Griebel et al, 2000). Outros teste nesta mesma categoria incluem o labirinto em zero elevado, o teste da caixa claro-escuro, o teste em campo aberto, e o teste de enterrar defensivo, este último particularmente importante, pois é o único dentre os anteriormente citados capaz de detectar os efeitos ansiolíticos dos inibidores eletivos da receptação de serotonina -ISRS (Cryan & Sweeney, 2011).…”

“…Como exemplo de outros testes incluídos nesta categoria podemos citar o teste de Geller-Seifter, o teste das quatro placas, dentre outros. O teste de Vogel e de Geller-Seifter são reconhecidos pelas suas baixas incidências de falsos positivos, mas são incapazes de detectar a ação ansiolítica de medicamentos ansiolíticos mais recentes como no caso dos inibidores seletivos da recaptação de serotonina (Cryan & Sweeney, 2011), o que não é o caso do teste das quatro placas, este já com a capacidade de detectar os efeitos ansiolíticos dos ISRS.…”