title: Rosmarinic acid protects against chronic ethanol-induced learning and memory deficits in rats.
abstract: OBJECTIVE
  Ethanol consumption induces neurological disorders including cognitive dysfunction. Oxidative damage is considered a likely cause of cognitive deficits. We aimed to investigate the effects of rosmarinic acid (RA) in different doses for 30 days on chronic ethanol-induced cognitive dysfunction using the passive avoidance learning (PAL) and memory task in comparison with donepezil, a reference drug. We also evaluated the levels of superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation in hippocampus as possible mechanisms.
  
  
  METHODS
  Memory impairment was induced by 15% w/v ethanol (2 g/kg, i.g.) administration for 30 days. RA (8, 16, and 32 mg/kg, i.g.) or donepezil (2 mg/kg, i.g.) was administered 30 minutes before ethanol. The acquisition trial was done 1 hour after the last administration of RA and donepezil. At the end, animals were weighed and hippocami were isolated for analyzing of oxidant/antioxidant markers.
  
  
  RESULTS
  Ethanol caused cognition deficits in the PAL and memory task. While RA 16 and 32 mg/kg improved cognition in control rats, it prevented learning and memory deficits of alcoholic groups. RA 8 mg/kg did not influence cognitive function in both control and alcoholic rats. RA 32 mg/kg had comparable effects with donepezil in prevention of acquisition and retention memory impairment. The higher doses of RA not only prevented increased lipid peroxidation and nitrite content but also decreased SOD, CAT, GSH, and FRAP levels in alcoholic groups and exerted antioxidant effects in non-alcoholic rats.
  
  
  CONCLUSIONS
  We showed that RA administration dose-dependently prevented cognitive impairment induced by chronic ethanol in PAL and memory and disturbed oxidant/antioxidant status as a possible mechanism. The antioxidant, anticholinesterase, and neuroprotective properties of RA may be involved in the observed effects. Therefore, RA represents a potential therapeutic option against chronic ethanol-induced amnesia which deserves consideration and further examination.
authors.affiliation: a Department of Biology , School of Basic Sciences, Bu-Ali Sina University , Hamedan , Iran.
authors.forename: Parisa
authors.initials: P
authors.lastname: Hasanein
authors.affiliation: a Department of Biology , School of Basic Sciences, Bu-Ali Sina University , Hamedan , Iran.
authors.forename: Rosa
authors.initials: R
authors.lastname: Seifi
authors.affiliation: b Department of Basic Veterinary Science , Faculty of Veterinary Medicine, University of Zabol , Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Hajinezhad
authors.affiliation: c Department of Plant Breeding and Biotechnology (PBB) , University of Zabol , Zabol , Iran.
authors.forename: Abbasali
authors.initials: A
authors.lastname: Emamjomeh
mesh_terms: D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D002934:Cinnamates / Q000008:administration & dosage / Q000627:therapeutic use*; D053630:Depsides / Q000008:administration & dosage / Q000627:therapeutic use*; D019587:Dietary Supplements; D000077265:Donepezil; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007189:Indans / Q000627:therapeutic use; D007859:Learning Disabilities / Q000209:etiology / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018697:Nootropic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D010880:Piperidines / Q000627:therapeutic use; D011897:Random Allocation; D017208:Rats, Wistar; D000097123:Rosmarinic Acid
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D002800:Cholinesterase Inhibitors; D002934:Cinnamates; D053630:Depsides; D000077265:Donepezil; D007189:Indans; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D010880:Piperidines; D000097123:Rosmarinic Acid
keywords: Donepezil; Ethanol; Learning; Memory; Rats; Rosmarinic acid