Cognitive performances of cholinergically depleted rats following chronic donepezil administration

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

Research output: Chapter in Book/Report/Conference proceedingChapter


Since acute and chronic administration of the acetylcholinesterase inhibitors (AChE-Is), namely of 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 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 AChE-Is, 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
Title of host publicationAdvances in Alzheimer's Disease
Number of pages20
Publication statusPublished - 2011

Publication series

NameAdvances in Alzheimer's Disease
ISSN (Print)22105727
ISSN (Electronic)22105735


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

ASJC Scopus subject areas

  • Clinical Neurology


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