The validity of animal models of predisposition to depression

Willner, Paul; Mitchell, Paul J.

doi:10.1097/00008877-200205000-00001

Cited by 378 publications

(220 citation statements)

References 136 publications

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“…Forced swim test (FST) is one of the most widely used protocols for studying both pharmacological and pathophysiological aspects of depression [21][22][23][24][25]. FST creates a situation of despair, and allows evaluation of the ability of the animal to adopt active strategies in inescapable stressful situation; failure to do so is indicative of a depression-like state [21,25] .…”

Section: Behavioral Testsmentioning

confidence: 99%

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Kindling epileptogenesis in immature rats leads to persistent depressive behavior

Mazarati¹,

Shin²,

Auvin³

et al. 2007

Epilepsy & Behavior

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Depression is a frequent comorbidity in epilepsy patients. A variety of biological factors may underlie epilepsy-associated depression. We examined whether kindling-induced chronic increase in seizure susceptibility is accompanied by behavioral symptoms of depression. Three week-old Wistar rats underwent rapid kindling -84 initially subconvulsant electrical stimulations of ventral hippocampus delivered every five minutes -followed by depression-specific behavioral tests performed two and four weeks later. Kindled animals exhibited sustained increase in the immobility time in the forced swim test and the loss of taste preference towards calorie-free saccharin, as compared to controls. Initial loss of preference towards the intake of calorie-containing sucrose was followed by the increased consumption at four weeks. At both time points, animals exhibited enhanced seizure susceptibility upon test stimulations of the hippocampus. We conclude that neuronal plastic changes associated with kindling state are accompanied by the development of depressive behavior.

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Section: Behavioral Testsmentioning

confidence: 99%

“…In rats, anhedonia can be assessed by the loss of taste preference; while normal animals prefer sweetened water over regular water, animals with depression do not exhibit such a preference [23,24,[28][29][30].…”

Section: Behavioral Testsmentioning

confidence: 99%

Kindling epileptogenesis in immature rats leads to persistent depressive behavior

Mazarati¹,

Shin²,

Auvin³

et al. 2007

Epilepsy & Behavior

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“…Unpredictable stressors have greater negative impact in humans than predictable ones, perhaps due to temporal uncertainty and inability to anticipate the event (see Anisman and Matheson, 2005;Willner and Mitchell, 2002). Thus, in the first experiment of the present study, both cognitive dysregulation and anxiety-like behavioral alterations induced by the chronic unpredictable stress (CUS) model of depression were assessed.…”

Section: Introductionmentioning

confidence: 97%

“…However, although many pre-clinical studies attempting to model aspects of depression have focused on behaviors thought to represent anhedonia, reduced locomotor activity or behavioral despair (eg, Lu et al, 2006;Rygula et al, 2005;Willner, 1997;Willner and Mitchell, 2002), relatively few have attempted to model cognitive impairments or state anxiety associated with depression.…”

Section: Introductionmentioning

confidence: 99%

Chronic Unpredictable Stress Induces a Cognitive Deficit and Anxiety-Like Behavior in Rats that is Prevented by Chronic Antidepressant Drug Treatment

Bondi

Rodríguez

Gould

et al. 2007

Neuropsychopharmacol

353

263

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Chronic stress is a risk factor for the development of many psychopathological conditions in humans, including major depression and anxiety disorders. There is a high degree of comorbidity of depression and anxiety. Moreover, cognitive impairments associated with frontal lobe dysfunction, including deficits in cognitive set-shifting and behavioral flexibility, are increasingly recognized as major components of depression, anxiety disorders, and other stress-related psychiatric illnesses. To begin to understand the neurobiological mechanisms underlying the cognitive and emotional consequences of chronic stress, it is necessary to employ an animal model that exhibits similar effects. In the present study, a rat model of chronic unpredictable stress (CUS) consistently induced a cognitive impairment in extradimensional set shifting capability in an attentional set shifting test, suggesting an alteration in function of the medial prefrontal cortex. CUS also increased anxiety-like behavior on the elevated plus-maze. Further, chronic treatment both with the selective norepinephrine reuptake blocker, desipramine (7.5 mg/kg/day), and the selective serotonin reuptake blocker, escitalopram (10 mg/kg/ day), beginning 1 week before CUS treatment and continuing through the behavioral testing period, prevented the CUS-induced deficit in extradimensional set-shifting. Chronic desipramine treatment also prevented the CUS-induced increase in anxiety-like behavioral reactivity on the plus-maze, but escitalopram was less effective on this measure. Thus, CUS induced both cognitive and emotional disturbances that are similar to components of major depression and anxiety disorders. These effects were prevented by chronic treatment with antidepressant drugs, consistent also with clinical evidence that relapse of depressive episodes can be prevented by antidepressant drug treatment.

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“…There are several animal models that can potentially be used to mimic these earlier events [reviewed in 58,88], including those based on exposure to acute or chronic low-grade stress (e.g., learned helplessness, forced swim test, and early social isolation) and selectively bred genetic models (e.g., Flinders sensitive line (FSL), Roman low-avoidance (RLA), and Fawn hooded (FH) lines) [reviewed in 88]. For a full review of models, see the special issue of Neuroscience and Biobehavioral Reviews (edited by A. Markou) devoted to the topic [52].…”

Section: Introductionmentioning

confidence: 99%

Social defeat, a paradigm of depression in rats that elicits 22-kHz vocalizations, preferentially activates the cholinergic signaling pathway in the periaqueductal gray

Kroes¹,

Burgdorf²,

Otto³

et al. 2007

Behavioural Brain Research

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Gene expression profiles in the periaqueductal gray (PAG) of adult Long-Evans rats as a function of a stressful social defeat in inter-male fighting encounters were examined. This social subordination model mimics prototypical behavioral changes that parallel aspects of clinical depression, has been postulated to simulate early changes in the onset of depression in the losers, and has been successfully utilized for the evaluation of antidepressant activity. 22-kHz ultrasonic vocalizations (USVs) have been shown to reflect negative emotional states akin to anxiety and depression. Social defeat is the most robust and reliable method of eliciting these calls. The PAG has been shown to be a key brain region for the generation of 22-kHz ultrasonic vocalizations, and 22-kHz USVs have been shown to be controlled by the mesolimbic cholinergic system. In this present study we examined gene expression changes in the PAG of social subordinate rats compared to dominant rats (that do not exhibit 22-kHz USVs). We found that social defeat significantly altered the genes associated with cholinergic synaptic transmission in the PAG. The most robust of these were the increased expression of the β2 subunit of the nicotinic acetylcholine receptor (CHRNB2) and the T-subunit of acetylcholinesterase (ACHE) in the subordinate animals. These changes were corroborated by qRT-PCR and found to be exclusive to the PAG compared to seven other brain regions examined. These data suggest that cholinergic transmission in the PAG is involved in the generation of 22-kHz USVs and provide potential therapeutic targets for the treatment of affective disorders.

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The validity of animal models of predisposition to depression

Cited by 378 publications

References 136 publications

Kindling epileptogenesis in immature rats leads to persistent depressive behavior

Kindling epileptogenesis in immature rats leads to persistent depressive behavior

Chronic Unpredictable Stress Induces a Cognitive Deficit and Anxiety-Like Behavior in Rats that is Prevented by Chronic Antidepressant Drug Treatment

Social defeat, a paradigm of depression in rats that elicits 22-kHz vocalizations, preferentially activates the cholinergic signaling pathway in the periaqueductal gray

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