Animal models of depression: are there any?

Abstract

Simple tests for antidepressant-like activity, such as 5-HTP-induced syndrome or reserpine-induced hypomotility, are often mechanism-based tests, pharmacologically specific for certain known classes of therapeutically successful antidepressant agents. Many of these behavioural assays have been superseded by neurochemical techniques such as in vivo microdialysis. In contrast to these mechanistic-based models, investigators have also endeavoured to reproduce in the laboratory, factors that are believed to precipitate depression in people. It is a strong assumption in this approach that depression is a response to stress. This strategy profiles the consequences of chronic stress particularly psychosocial stress or early life events, in order to reproduce in animals the behavioural signs and pathologies associated with depression. The advances in the social psychological, clinical pathological and new areas such as neuroimaging research offer the possibility of establishing more sophisticated models for depression in animals with a broader range of biomarkers from the immunological and endocrinological to neurochemical and behavioural. Combining these novel insights with more traditional tests of depression may not only increase our understanding of the neurobiology of depression but also afford more precise and predictive preclinical models of depression. The responsiveness of different strains or genetically modified animals to stress is likely to be a key area of study. Furthermore we must look to individual differences in subjects, even within the same strain, to more fully understand why some individuals show pathological responses to stress whereas others appear unaffected. Conversely in validating our models using currently available treatments we must include the concept of non-responders so as not to disregard models that may extend therapeutic possibilities in these patients.

Neurochemical and Behavioural Changes in Rat Models of Depression

“…However, there have been numerous models investigated, but many of them do not possess all three of the above noted characteristics, and, as such, will not be discussed in this review. O'Neil and Moore 11 wrote: "the OBX test is valuable in that it has been one of the few tests that mimics the slow onset of antidepressant action reported in clinical studies" and concluded that "the convergence of data from markers as diverse as behaviour, neurochemistry, as well as endocrine and immune function, suggest that this model will continue to shed valuable light on depressive mechanisms and treatment for some time to come".…”

“…7,[10][11][12][13] Neuronal changes have been reported in structures deemed to play an important role in affective and cognitive functioning, which are also the target of the olfactory bulb projections, such as the amygdala, greater hippocampal formation, and the bed nucleus of the stria terminalis. 10,14 The amygdala and hippocampus have important influences on frontal cortical striatal circuitry.…”

Serotonin a la carte: Supplementation with the serotonin precursor 5-hydroxytryptophan

“…Evidence for antidepressant efficacy of 5-hydroxytryptophan 3.1. Preclinical evidence for efficacy of 5-hydroxytryptophan 5-HTP is commonly given to rats or mice to test the SSRI potency of putative antidepressants (O'Neil & Moore, 2003). This simple in vivo test measures the potency of a compound in potentiating the serotonin syndrome induced by the administration of 5-HTP (Grahame- Smith, 1971).…”

Anksiyete araştırmalarında kullanılan sıçan davranış modelleri

“…Sıçanın açık kolu görecek şekilde labirent üzerine yerleştirilmesinin nedeni, sıçanların doğuştan açık ve yüksek yerlerden korkuyor olmalarıdır [4,24]. Anksiyeteye işaret eden davranış değerlendirmeleri; kapalı kol üzerinde geçen zamanın uzaması, donakalma süresindeki artış, açık kola giriş sayısındaki azalma, merkezi alanda gezinme süresindeki azalma ve iki ayağı üzerinde kalkıp havayı koklama sayısındaki ve süresindeki artışlardır [25].…”

“…Sıçanlar için koku alma temel duyu modalitesi olduğundan, olfakter bulbuslarının bilateral olarak alınması ile depresyon yaratılmaktadır [25,34]. Bu modelin kullanıldığı antidepresan aktivite değerlendirme çalışmalarında, sıçanların açık alandaki davranışlarında hiperaktivite azalması kaydedilmiştir [35].…”