Chronic mild stress-induced anhedonia: A realistic animal model of depression

Willner, Paul; Muscat, Richard; Papp, Mariusz

doi:10.1016/s0149-7634(05)80194-0

Cited by 1,041 publications

(635 citation statements)

References 75 publications

Supporting

Mentioning

586

Contrasting

Unclassified

Order By: Relevance

“…Indeed, our data are consistent with the previous findings that rats exposed to stressors consume less sucrose than the controls [13,18,24,26] . This indicates that anhedonia, the core symptom of depression, can be induced by CUMS in rats.…”

supporting

confidence: 93%

See 1 more Smart Citation

Increased expression level of corticotropin-releasing hormone in the amygdala and in the hypothalamus in rats exposed to chronic unpredictable mild stress

et al. 2010

View full text Add to dashboard Cite

Objective Corticotropin-releasing hormone (CRH) plays an important role in neuroendocrine, autonomic and behavioral responses to stressors. In the present study, the effect of chronic unpredictable mild stress (CUMS) on CRH neurons was investigated in rat brain. Methods The rats were exposed to one of the stressors each day for 21 d. Immunostaining was performed to detect the CRH-positive neurons in the paraventricular nucleus (PVN) of the hypothalamus and in amygdala.Results After the stress protocol, the animals showed a reduction in body weight gain as well as reduced sucrose preference and locomotor activity. Interestingly, the CRH neurons in both PVN and central nucleus of the amygdala (CeA) were stimulated by CUMS. The densities of CRH-containing neurons in both PVN and CeA were significantly higher than those in control group. Conclusion The CRH systems in PVN and CeA may both contribute to depression-like behaviors during CUMS.

show abstract

supporting

confidence: 93%

“…The protocol is regarded to closely mimic the human situation, consisting of more daily hassles than traumatic events [23] . The attenuated preference for solution serves as a marker of generalized decrease of sensitivity to reward, that is, anhedonia [18,[22][23][24][25] .…”

mentioning

confidence: 99%

Increased expression level of corticotropin-releasing hormone in the amygdala and in the hypothalamus in rats exposed to chronic unpredictable mild stress

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Overall, the effects of SR58611A in the CMS paralleled those of repeated treatment with fluoxetine. Based on the well-accepted predictive validity of the CMS (Willner et al, 1992), the present findings indicate that SR58611A has antidepressant-like properties that are comparable in terms of efficacy of the effects to those of fluoxetine. Supporting these behavioral data, our electroencephalographic results show that SR58611A modified spontaneous sleep parameters in a manner comparable to that observed with fluoxetine.…”

Section: Discussionmentioning

confidence: 53%

“…The CMS protocol is based on a protocol originally designed by Willner et al (1992) for rats and by Griebel et al (2002b) for mice. The protocol consists of the sequential and unpredictable application of a variety of mild stressors (for example, restraint, forcedswimming, water and/or food deprivation) during 6 weeks (Griebel et al, 2002a, b).…”

Section: The Pinch-induced Tonic Immobility Paradigm In Gerbilsmentioning

confidence: 99%

Stimulation of the β3-Adrenoceptor as a Novel Treatment Strategy for Anxiety and Depressive Disorders

Stemmelin

Cohen

Terranova

et al. 2007

Neuropsychopharmacol

108

View full text Add to dashboard Cite

The characterization of the first selective orally active and brain-penetrant b 3 -adrenoceptor agonist, SR58611A (amibegron), has opened new possibilities for exploring the involvement of this receptor in stress-related disorders. By using a battery of tests measuring a wide range of anxiety-related behaviors in rodents, including the mouse defense test battery, the elevated plus-maze, social interaction, stressinduced hyperthermia, four-plate, and punished drinking tests, we demonstrated for the first time that the stimulation of the b 3 receptor by SR58611A resulted in robust anxiolytic-like effects, with minimal active doses ranging from 0.3 to 10 mg/kg p.o., depending on the procedure. These effects paralleled those obtained with the prototypical benzodiazepine anxiolytic diazepam or chlordiazepoxide.Moreover, when SR58611A was tested in acute or chronic models of depression in rodents, such as the forced-swimming and the chronic mild stress tests, it produced antidepressant-like effects, which were comparable in terms of the magnitude of the effects to those of the antidepressant fluoxetine or imipramine. Supporting these behavioral data, SR58611A modified spontaneous sleep parameters in a manner comparable to that observed with fluoxetine. Importantly, SR58611A was devoid of side effects related to cognition (as shown in the Morris water maze and object recognition tasks), motor activity (in the rotarod), alcohol interaction, or physical dependence. Antagonism studies using pharmacological tools targeting a variety of neurotransmitters involved in anxiety and depression and the use of mice lacking the b 3 adrenoceptor suggested that these effects of SR58611A are mediated by b 3 adrenoceptors. Taken as a whole, these findings indicate that the pharmacological stimulation of b 3 adrenoceptors may represent an innovative approach for the treatment of anxiety and depressive disorders.

show abstract

“…The CMS protocol, originally described by Willner et al (1992) for rats, was adapted from the one described by Griebel et al (2002) for mice. It consisted in the sequential application of a variety of mild stressors, including restraint, forced swimming, water and/or food deprivation, pairing with another stressed animal, each applied for a period ranging from 2 to 24 h, in a schedule lasting 36 days.…”

Section: Effect Of Ssr180711 In a Cms Procedures In Micementioning

confidence: 99%

SSR180711, a Novel Selective α7 Nicotinic Receptor Partial Agonist: (II) Efficacy in Experimental Models Predictive of Activity Against Cognitive Symptoms of Schizophrenia

Pichat

Bergis

Terranova

et al. 2006

Neuropsychopharmacol

235

155

View full text Add to dashboard Cite

SSR180711 (4-bromophenyl 1,4diazabicyclo(3.2.2) nonane-4-carboxylate, monohydrochloride) is a selective a7 nicotinic receptor (n-AChR) partial agonist. Based on the purported implication of this receptor in cognitive deficits associated with schizophrenia, the present study assessed efficacy of SSR180711 (i.p. and p.o.) in different types of learning and memory involved in this pathology. SSR180711 enhanced episodic memory in the object recognition task in rats and mice (MED: 0.3 mg/kg), an effect mediated by the a7 n-AChR, as it was no longer seen in mice lacking this receptor. Efficacy was retained after repeated treatment (eight administrations over 5 days, 1 mg/kg), indicating lack of tachyphylaxia. SSR180711 also reversed (MED: 0.3 mg/kg) MK-801-induced deficits in retention of episodic memory in rats (object recognition). The drug reversed (MED: 0.3 mg/kg) selective attention impaired by neonatal phencyclidine (PCP) treatment and restored MK-801-or PCP-induced memory deficits in the Morris or linear maze (MED: 1-3 mg/kg). In neurochemical and electrophysiological correlates of antipsychotic drug action, SSR180711 increased extracellular levels of dopamine in the prefrontal cortex (MED: 1 mg/kg) and enhanced (3 mg/kg) spontaneous firing of retrosplenial cortex neurons in rats. Selectivity of SSR180711 was confirmed as these effects were abolished by methyllycaconitine (3 mg/kg, i.p. and 1 mg/kg, i.v., respectively), a selective a7 n-AChR antagonist. Additional antidepressant-like properties of SSR180711 were demonstrated in the forced-swimming test in rats (MED: 1 mg/kg), the maternal separation-induced ultrasonic vocalization paradigm in rat pups (MED: 3 mg/kg) and the chronic mild stress procedure in mice (10 mg/kg o.d. for 3 weeks). Taken together, these findings characterize SSR180711 as a promising new agent for the treatment of cognitive symptoms of schizophrenia. The antidepressant-like properties of SSR180711 are of added interest, considering the high prevalence of depressive symptoms in schizophrenic patients.

show abstract

Chronic mild stress-induced anhedonia: A realistic animal model of depression

Cited by 1,041 publications

References 75 publications

Increased expression level of corticotropin-releasing hormone in the amygdala and in the hypothalamus in rats exposed to chronic unpredictable mild stress

Increased expression level of corticotropin-releasing hormone in the amygdala and in the hypothalamus in rats exposed to chronic unpredictable mild stress

Stimulation of the β3-Adrenoceptor as a Novel Treatment Strategy for Anxiety and Depressive Disorders

SSR180711, a Novel Selective α7 Nicotinic Receptor Partial Agonist: (II) Efficacy in Experimental Models Predictive of Activity Against Cognitive Symptoms of Schizophrenia

Contact Info

Product

Resources

About