title: Stress-induced anhedonia is associated with an increase in Alzheimer's disease-related markers.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: Dpto Farmacologia, Universidad de Navarra, Pamplona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Briones
authors.forename: S
authors.initials: S
authors.lastname: Gagno
authors.forename: E
authors.initials: E
authors.lastname: Martisova
authors.forename: M
authors.initials: M
authors.lastname: Dobarro
authors.forename: B
authors.initials: B
authors.lastname: Aisa
authors.forename: M
authors.initials: M
authors.lastname: Solas
authors.forename: R
authors.initials: R
authors.lastname: Tordera
authors.forename: Mj
authors.initials: M
authors.lastname: Ramírez
mesh_terms: D000544:Alzheimer Disease; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D059445:Anhedonia / Q000187:drug effects*; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D003071:Cognition / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003511:Cyclohexanols / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism*; D013395:Sucrose / Q000008:administration & dosage; D016708:Synaptophysin; D000069470:Venlafaxine Hydrochloride; D033921:Vesicular Transport Proteins / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018687:Antidepressive Agents, Second-Generation; D015415:Biomarkers; D003511:Cyclohexanols; C489131:Mapt protein, rat; D016708:Synaptophysin; C569016:Syp protein, rat; D033921:Vesicular Transport Proteins; D016875:tau Proteins; D013395:Sucrose; D000069470:Venlafaxine Hydrochloride; D051057:Proto-Oncogene Proteins c-akt; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat; D003345:Corticosterone