title: Antidepressant, anxiolytic and procognitive effects of rivastigmine and donepezil in the chronic mild stress model in rats.
abstract: BACKGROUND
  The treatment of depression in old age is complicated by frequent co-morbidity with cognitive impairment. Anti-dementia drugs have some efficacy to improve cognitive performance and there is an inconsistent literature regarding the effect of such drugs on depressive symptoms. Here, we have investigated whether anti-dementia drugs would have antidepressant-like and pro-cognitive effects in a well-validated animal model of depression and cognitive impairment, chronic mild stress (CMS).
  
  
  METHODS
  Rats were subjected to CMS for a total of 8 weeks. After 2 weeks, subgroups of stressed and non-stressed animals were treated daily, for 5 weeks followed by 1 week of drug withdrawal, with vehicle, imipramine (10 mg/kg), rivastigmine (2 mg/kg), donepezil (0.3 mg/kg) or memantine (5 mg/kg). Sucrose intake was tested weekly, and animals were also tested in the elevated plus maze (at week 7) and in an object recognition task (at weeks 7 and 8).
  
  
  RESULTS
  CMS decreased sucrose intake, had an anxiogenic effect in the elevated plus maze, and impaired performance in the object recognition test. Imipramine, rivastigmine and donepezil normalized performance in all three tests. Memantine had anxiolytic and pro-cognitive effects, but did not reverse CMS-induced anhedonia.
  
  
  CONCLUSIONS
  The fact that all three anti-dementia drugs reversed CMS-induced cognitive impairment and that cholinesterase inhibitors, but not memantine, have antidepressant-like effects in this model suggest that different mechanisms may underlie CMS-induced anhedonia and cognitive impairment. We discuss the clinical implications of these findings.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343, Krakow, Poland. nfpapp@cyfronet.pl.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Papp
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343, Krakow, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Gruca
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343, Krakow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Lason-Tyburkiewicz
authors.affiliation: Department of Psychology, Swansea University, Swansea, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Willner
mesh_terms: D059445:Anhedonia / Q000187:drug effects; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D060825:Cognitive Dysfunction / Q000188:drug therapy*; D003866:Depressive Disorder / Q000188:drug therapy*; D004195:Disease Models, Animal; D000077265:Donepezil; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018697:Nootropic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D000068836:Rivastigmine / Q000494:pharmacology / Q000627:therapeutic use*; D013315:Stress, Psychological / Q000188:drug therapy*
chemical_list: D000928:Antidepressive Agents; D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil; D000068836:Rivastigmine
keywords: Anhedonia; Cholinesterase inhibitors; Chronic mild stress; Donepezil; Imipramine; Memantine; Object recognition; Rat; Rivastigmine