Cognitive performances of cholinergically depleted rats following chronic donepezil administration

Debora Cutuli, Francesca Foti, Laura Mandolesi, Paola De Bartolo, Francesca Gelfo, Francesca Federico, Laura Petrosini

Research output: Contribution to journalArticlepeer-review


Since acute and chronic administration of the acetylcholinesterase inhibitors, namely donepezil, improves cognitive functions in patients afflicted by mild to moderate dementia and reverses memory deficits in experimental models of learning and memory, it seemed interesting to assess the effects of chronic donepezil treatment on cognitive functions in adult rats with forebrain cholinergic depletion. Lesions were performed by means of intracerebroventricular injections of the immunotoxin 192 IgG-saporin. The cognitive functions of lesioned animals treated or not treated with donepezil were compared with those of intact animals. Cholinergic depletion affected working memory functions, weakened procedural competencies, affected the acquisition of localizing knowledge, and evoked remarkable compulsive and perseverative behaviors. In lesioned animals, chronic donepezil treatment ameliorated localizatory capabilities, performances linked to cognitive flexibility and procedural abilities. Furthermore, it attenuated compulsive deficits. The present data indicate positive effects of chronic donepezil treatment on specific cognitive performances, suggesting that an aimed use of acetylcholinesterase inhibitors, targeting some symptoms more than others, may be beneficial in the case of cholinergic hypofunction. The animal model used in the present research may provide an efficient method for analyzing cognition-enhancing drugs before clinical trials.

Original languageEnglish
Pages (from-to)161-176
Number of pages16
JournalJournal of Alzheimer's Disease
Issue number1
Publication statusPublished - 2009


  • 192 IgG-saporin
  • Acetylcholinesterase inhibitor
  • Behavioral testing
  • Cholinergic neurotransmission
  • Cognitive flexibility
  • Forebrain cholinergic system
  • Mnesic functions

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology


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