Donepezil, a centrally acting acetylcholinesterase inhibitor, alleviates learning deficits in hypocholinergic models in rats

Methods Find Exp Clin Pharmacol. 2000 Mar;22(2):89-95. doi: 10.1358/mf.2000.22.2.796070.


Donepezil is a member of a new class of centrally acting cholinesterase inhibitors which preferentially inhibit acetylcholinesterase rather than butyrylcholinesterase. The effects of donepezil on learning impairments were investigated in some hypocholinergic models in rats. In nucleus basalis magnocellularis (NBM)-lesioned rats, donepezil alleviated deficits in passive avoidance response at a dose of 0.125 mg/kg and higher, while tacrine had only a tendency toward improved performance. Donepezil at 0.5 mg/kg effectively counteracted acquisition impairments in the water maze task induced by lesions of the medial septum; tacrine had no significant effects on impairments in this task. Scopolamine caused an increase of errors in the 8-arm radial maze. Donepezil significantly decreased scopolamine-induced errors in the radial maze at 0.5 mg/kg, whereas tacrine decreased errors at 2 mg/kg. These results suggest that donepezil can clearly minimize learning impairments induced by treatments that cause central cholinergic deficiencies in rats. These findings support the clinical efficacy of donepezil in Alzheimer's disease.

MeSH terms

  • Animals
  • Avoidance Learning / drug effects
  • Basal Nucleus of Meynert / drug effects*
  • Basal Nucleus of Meynert / physiology
  • Cholinesterase Inhibitors / therapeutic use*
  • Donepezil
  • Dose-Response Relationship, Drug
  • Indans / therapeutic use*
  • Learning Disabilities / drug therapy*
  • Male
  • Maze Learning / drug effects
  • Piperidines / therapeutic use*
  • Rats
  • Rats, Wistar
  • Scopolamine / pharmacology
  • Tacrine / therapeutic use


  • Cholinesterase Inhibitors
  • Indans
  • Piperidines
  • Tacrine
  • Donepezil
  • Scopolamine