Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant

Willner, Paul; Towell, Anthony; Sampson, David; Sophokleous, S; Muscat, Richard

doi:10.1007/bf00187257

Cited by 1,718 publications

(1,296 citation statements)

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“…There were significant decreases in sucrose preference in depressive animal induced by CUMS as expected (po0.001; Willner et al, 1987;De Vry and Schreiber, 1997;Willner, 1997). Treatment with 54 mg/kg/ day mifepristone in the last 7 of 21 days of CUMS significantly increased sucrose preference (po0.01), whereas 4.5 mg/kg/day mifepristone had no obvious effect on sucrose preference (Figure 1).…”

Section: Sucrose Preference Testsupporting

confidence: 75%

“…In the present study, we used the rat model of depression induced by CUMS, which mimic a series of life events. CUMS has shown to produce behavioral and neuroendocrine changes in rats similar to major depression in human (Willner et al, 1987;De Vry and Schreiber, 1997;Willner, 1997). Patients with psychotic major depression are characterized by abnormalities in the HPA axis activity, for example, elevated urinary free cortisol levels and plasma adrenocorticotropin hormone, as well as the highest rates of nonsuppression on the dexamethasone suppression test (Belanoff et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Compared to repeated restraint stress, CUMS produced the same degree of apical dendritic atrophy in CA3 pyramidal neurons (Magarinos and McEwen, 1995b). As an animal model of depression, the advantage of the CUMS model is that this procedure simulates anhedonia, a loss of responsiveness to pleasant events, which is a core symptom of depression and the defining feature of melancholia (Willner et al, 1987;De Vry and Schreiber, 1997;Willner, 1997). We chose the standard use of sucrose preference as the parameter of anhedonia, instead of sucrose consumption, because some data suggested that preference appears to be more sensitive to CUMS than intake (De Vry and Schreiber, 1997).…”

Section: Discussionmentioning

confidence: 99%

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Mifepristone Repairs Region-Dependent Alteration of Synapsin I in Hippocampus in Rat Model of Depression

Han

Wang

et al. 2007

Neuropsychopharmacol

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Clinical investigations present much evidence that the glucocorticoid receptor (GR) antagonist mifepristone leads to a rapid amelioration of depression. The molecular mechanisms of mifepristone involved in the treatment of depression are not fully understood. Depression is associated with hippocampal plasticity, for which increased excitatory amino acid (EAA) release in CA3 induced by chronic stress is responsible, and glucocorticoids have a permissive role and act synergistically with EAAs in producing neuronal damage. Moreover, glucocorticoids increase synapsin I, which has a key role in the release of neurotransmitter, including EAAs. Hereby, we hypothesize that major depression involves synapsin I alteration and that mifepristone blocks this alteration. In the present study, we observed both the expression of hippocampal synapsin I and depression-associated behavior in a rat model of depression induced by chronic unpredictable mild stress (CUMS). The result showed that a region-dependent synapsin I alteration occurs in the rat hippocampus after 21 days of CUMS, that is, it increases in dentate gyrus (DG)/CA3 and decreases in the CA1 region. Correlation analysis indicated that the decrease of synapsin I in CA1 is highly correlated with the increase in the DG/CA3 subfield. Simultaneously, the region-dependent alteration of synapsin I is correlated with depression-associated behaviors. Both the alteration of synapsin I and the depression-associated behavior were rapidly restored after treatment with mifepristone for 1 week. The result suggests that the molecular mechanism underlying the treatment of depression with mifepristone is associated with the rapid repair of the synaptic alteration.

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Section: Sucrose Preference Testsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Mifepristone Repairs Region-Dependent Alteration of Synapsin I in Hippocampus in Rat Model of Depression

Han

Wang

et al. 2007

Neuropsychopharmacol

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“…In this study, we observed that rats submitted to chronic administration of H-BCAA have a decreased sweet food intake and increased adrenal gland weight, without any alteration of body weight compared with the control group. This mimics anhedonia, a key depressive symptom (Katz et al 1981b;Willner et al 1987Willner et al , 1998. We also observed an increase in immobility time in the H-BCAA group during the forced swimming test.…”

Section: Discussionsupporting

confidence: 63%

Behavioral Responses in Rats Submitted to Chronic Administration of Branched-Chain Amino Acids

et al. 2013

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Maple syrup urine disease (MSUD) is an inborn metabolism error caused by a deficiency of branched-chain a-keto acid dehydrogenase complex activity. This blockage leads to an accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine, as well as their corresponding a-keto and a-hydroxy acids. Previous reports suggest that MSUD patients are at high risk for chronic neuropsychiatric problems. Therefore, in this study, we assessed variables that suggest depressive-like symptoms (anhedonia as measured by sucrose intake, immobility during the forced swimming test and body and adrenal gland weight) in rats submitted to chronic administration of BCAA during development. Furthermore, we determined if these parameters were sensitive to imipramine and N-acetylcysteine/deferoxamine (NAC/DFX). Our results demonstrated that animals subjected to chronic administration of branched-chain amino acids showed a decrease in sucrose intake without significant changes in body weight. We also observed an increase in adrenal gland weight and immobility time during the forced swimming test. However, treatment with imipramine and NAC/DFX reversed these changes in the behavioral tasks. In conclusion, this study demonstrates a link between MSUD and depression in rats. Moreover, this investigation reveals that the antidepressant action of NAC/DFX and imipramine might be associated with their capability to maintain pro-/anti-oxidative homeostasis.

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“…The CUS procedure is a modification of published procedures (Katz et al, 1981;Lu et al, 2006;Willner et al, 1987). One day before beginning the chronic unpredictable stress, rats were housed individually, and the CUS procedure was then applied for 14 consecutive days, as outlined in Table 1.…”

Section: Chronic Unpredictable Stress Proceduresmentioning

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

346

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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Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant

Cited by 1,718 publications

References 29 publications

Mifepristone Repairs Region-Dependent Alteration of Synapsin I in Hippocampus in Rat Model of Depression

Mifepristone Repairs Region-Dependent Alteration of Synapsin I in Hippocampus in Rat Model of Depression

Behavioral Responses in Rats Submitted to Chronic Administration of Branched-Chain Amino Acids

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

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