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We have studied mechanisms implicated in vulnerability to stress and the relationship with changes in AD\u2010related markers.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold> 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\u2003mg\u00b7kg<jats:sup>\u22121<\/jats:sup> 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 \u03b2\u2010protein (A\u03b2), \u03b2\u2010secretase (BACE1) and \u03c4 phosphorylation, were measured in the hippocampus.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold> After CMS, 40% of rats were resistant to the development of anhedonia (CMS\u2010resistant to stress), whereas the remaining were responsive [CMS\u2010anhedonic (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 A\u03b240, BACE1 and \u03c4 phosphorylation were also found only in CMSA rats. All these effects in CMSA rats were reverted by treatment with venlafaxine.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold> 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\u2010related disorders, including AD.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01602.x","type":"journal-article","created":{"date-parts":[[2011,7,28]],"date-time":"2011-07-28T11:11:36Z","timestamp":1311851496000},"page":"897-907","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Stress\u2010induced anhedonia is associated with an increase in Alzheimer's disease\u2010related 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