Cognitive performances of cholinergically depleted rats following chronic donepezil administration

Abstract. Since acute and chronic administration of the acetylcholinesterase inhibitors, namely donepezil, improves cognitive functions in patients affiicted by mild to moderate dementia and reverses memory deficits in experimental models of leaming 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 oflesioned 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 oflocalizing knowledge, and evoked remarkable compulsive and perseverative behaviors. In lesioned animals, chronic donepezil treatment ameliorated localizatory capabilities, performances linked to cognitive f1exibility 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 beneficiai in the case of cholinergic hypofunction. The animai model used in the present research may provide an efficient method for analyzing cognition-enhancing drugs before clinical trials.