Animal Models of Depression: A Diathesis/Stress Approach

Willner, Paul; Mitchell, Paul J.

doi:10.1002/0470854871.chxviii1

Cited by 20 publications

(27 citation statements)

References 230 publications

(290 reference statements)

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“…An evaluation of the CMS procedure as an animal model of depression suggests that this model has a unique combination of predictive validity (pharmacological profi le), face validity (symptom profi le) and construct validity (theoretical rationale) [5,8] .…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the major focus is on the reproducibility of the CMS procedure, and there is only passing discussion of some important issues bearing on the validity of CMS as a model of depression, which are considered in more detail elsewhere [5,7,8] . Given that criticism of the CMS procedure extends not only to the consistency of the behavioural effects but also to 'the palliative effect of antidepressants' [14] , it seemed apposite to include also an overview of treatment studies, which, contrary to the above claim, are almost unanimous in reporting that antidepressant treatment reverses or prevents the depressive-like behavioural effects of CMS.…”

Section: Introductionmentioning

confidence: 99%

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Chronic Mild Stress (CMS) Revisited: Consistency and Behavioural-Neurobiological Concordance in the Effects of CMS

Willner¹

2005

Neuropsychobiology

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1,445

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The chronic mild stress (CMS) model of depression has high validity but has in the past been criticized for being difficult to replicate. However, a large number of recent publications have confirmed that CMS causes behavioural changes in rodents that parallel symptoms of depression. This review summarizes studies from over sixty independent research groups that have reported decreases in reactivity to rewards, and a variety of other depression-like behaviours, in rats or mice, following exposure to CMS. Together, these changes are referred to as a ‘depressive’ behavioural profile. Almost every study that has examined the effects of chronic antidepressant treatment in these procedures has reported that antidepressants were effective in reversing or preventing these ‘depressive’ behavioural changes. (The single exception is a study in which the duration of treatment was too brief to constitute an adequate trial.) There are also a handful of reports of CMS causing significant effects in the opposite direction, termed here an ‘anomalous’ behavioural profile. There are six neurobiological parameters that have been studied in both ‘anhedonic’ and ‘anomalous’ animals: psychostimulant and place-conditioning effects of dopamine agonists; dopamine D₂ receptor number and message; inhibition of dopamine turnover by quinpirole, and beta-adrenergic receptor binding. On all six measures, CMS caused opposite effects in animals displaying ‘depressive’ and ‘anomalous’ profiles. Thus, there is overwhelming evidence that under appropriate experimental conditions, CMS can cause antidepressant-reversible depressive-like effects in rodents; however, the ‘anomalous’ profile that is occasionally reported appears to be a genuine phenomenon, and these two sets of behavioural effects appear to be associated with opposite patterns of neurobiological changes.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chronic Mild Stress (CMS) Revisited: Consistency and Behavioural-Neurobiological Concordance in the Effects of CMS

Willner¹

2005

Neuropsychobiology

Self Cite

1,445

1,023

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“…El análisis por AAC indica que una sola curva describe todos los datos, confirmando la reproducibilidad del modelo optimizado y su aplicabilidad para el estudio de la farmacodinamia de agentes antidiabéticos. y ha sido esencial para estudiar la farmacodinamia de medicamentos en enfermedades infecciosas (22) o en psiquiatría (23).…”

Section: Discussionunclassified

“…Esta mejora implica un ahorro de recursos derivado de tener la especie alojada una semana menos en el bioterio, así como incrementar el número de experimentos posibles en un año calendario. Además, la cepa exocriada es una ventaja para los estudios en farmacología, pues imita la variación interindividual observada en humanos (23). Los resultados confirman que el modelo de Garza y colaboradores es reproducible en una cepa de ratones exocriados, y nuestro aporte novedoso fue utilizar dicho modelo para describir por primera vez los parámetros farmacodinámicos primarios de la insulina regular (E max y ED 50 ).…”

Section: Discussionunclassified

Obtención De Un Modelo Múrido De Diabetes Inducida Por Estreptozotocina Útil en La Evaluación Farmacodinámica De La Insulina Regular

Valencia

Zuluaga²,

Jaramillo³

et al. 2017

Vitae

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RESUMENAntecedentes: Existen múltiples modelos animales de diabetes, pero todavía no se ha validado uno útil para determinar la farmacodinamia de medicamentos. Objetivos. Usar el modelo de inducción de diabetes mediante estreptozotocina equilibrada en ratones no emparentados, para determinar de forma precisa y reproducible la farmacodinamia de insulina regular. Métodos. En ratones machos no emparentados de aproximadamente 37 g, se inyectó una dosis intraperitoneal de 150 mg/kg de una solución equilibrada de estreptozotocina. La glucemia (mg/dL) se midió a los 0, 7, 9, 14, 16, 17 y 18 días post-inducción. Una vez los ratones alcanzaron glucemias >300 mg/dL, se determinó la eficacia hipoglucemiante de insulina regular en tres experimentos independientes. El rango de dosis fue 0,25 UI/kg a 4 UI/kg. Una ecuación de decaimiento exponencial de dos parámetros se ajustó a los datos. Resultados. Al día 18, el modelo tuvo una efectividad del 80% para producir diabetes (glucemia 446 ± 59 mg/dL), con mortalidad de sólo 2%. El coeficiente de variación intra e interexperimento fue ≤13%. Los parámetros farmacodinámicos de insulina fueron indistinguibles después de tres experimentos (P=0,32). La magnitud del efecto máximo fue -374 ± 30,7 mg/dL y la dosis efectiva 50 fue 1,34 ± 0,2 UI/kg. Conclusión. El modelo de diabetes inducida por estreptozotocina equilibrada permitió determinar de manera reproducible la farmacodinamia de la insulina regular.Palabras clave: Diabetes Inducida por Estreptozotocina, Estreptozotocina, Insulina, Modelos Animales de Enfermedad, Farmacología. ABSTRACTBACKGROUND. There are multiple animal models of diabetes, but still no one has been validated useful to determine the pharmacodynamics of drugs. Objectives: To use the streptozotocin-induced model of diabetes in outbred mice, to reliably determine the pharmacodynamics of regular insulin. Methods. Outbred mice weighing 37 g in average, were injected by intraperitoneal route with 150 mg/ kg of an equilibrated solution of streptozotocin. Blood glucose (mg/dL) was measured at 0,7,9,14,16,17

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“…He had devised a frequently cited model for making rats either depressed or stressed. 15 The model was based on the drinking of a glucose solution by the rats: if they were stressed, they drank less. He asked a PhD student to be an investigator in an early trial of a new anxiolytic produced by a French pharmaceutical company, using the model to see if the stressed rats became less stressed after ingesting the anxiolytic.…”

Section: My Own More Recent Experiencementioning

confidence: 99%

The Stoke CNEP Saga – did it need to take so long?

Wells

2010

J R Soc Med

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Animal Models of Depression: A Diathesis/Stress Approach

Cited by 20 publications

References 230 publications

Chronic Mild Stress (CMS) Revisited: Consistency and Behavioural-Neurobiological Concordance in the Effects of CMS

Chronic Mild Stress (CMS) Revisited: Consistency and Behavioural-Neurobiological Concordance in the Effects of CMS

Obtención De Un Modelo Múrido De Diabetes Inducida Por Estreptozotocina Útil en La Evaluación Farmacodinámica De La Insulina Regular

The Stoke CNEP Saga – did it need to take so long?

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