Stress‐induced anhedonia is associated with an increase in Alzheimer's disease‐related markers

British Journal of Pharmacology - Tập 165 Số 4 - Trang 897-907 - 2012
Alejandro Fernández Briones1,2, Sara Gagno1, Eva Martišová1, Marta Dobarro1, Bárbara Aisa1, Maite Solas1, Rosa M. Tordera1, Marı́a J. Ramı́rez3,1
1Dpto Farmacologia, Universidad de Navarra, Pamplona, Spain
2Universidad Autónoma de Chiapas, Chiapas, México
3Division of Neurosciences, CIMA, Pamplona, Spain

Tóm tắt

BACKGROUND AND PURPOSE Stress is believed to be associated with the development of neuropsychiatric disorders, including Alzheimer's disease (AD). We have studied mechanisms implicated in vulnerability to stress and the relationship with changes in AD‐related markers.EXPERIMENTAL APPROACH Anhedonia induced by a chronic mild stress (CMS) procedure, applied for 6 weeks, was used to select rats vulnerable or resistant to stress. Sucrose intake, the Porsolt forced swimming test and cognitive deficits in the novel object recognition test (NORT) were used to characterize vulnerable and resilient rats. The antidepressant venlafaxine (20 mg·kg−1 p.o.) or saline was administered daily during the last 2 weeks of CMS. Biochemical markers affected by stress, PKB, ERK and synaptophysin, and those associated with AD, amyloid β‐protein (Aβ), β‐secretase (BACE1) and τ phosphorylation, were measured in the hippocampus.KEY RESULTS After CMS, 40% of rats were resistant to the development of anhedonia (CMS‐resistant to stress), whereas the remaining were responsive [CMS‐anhedonic (CMSA)]. Only CMSA rats displayed significant increases in immobility time in the forced swimming test and cognitive deficits in the NORT, and significant decreases in synaptophysin, phosphorylated PKB and phosphorylated ERK1/2 expression in the hippocampus. Increased levels of Aβ40, BACE1 and τ phosphorylation were also found only in CMSA rats. All these effects in CMSA rats were reverted by treatment with venlafaxine.CONCLUSIONS AND IMPLICATIONS Vulnerability to stress might constitute a risk factor for the development of AD, and pharmacological treatment with venlafaxine may represent a therapeutic strategy for the treatment of stress‐related disorders, including AD.

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British Journal of Pharmacology

Tập 165 Số 4

897-907

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