Cognitive performances of cholinergically depleted rats following chronic donepezil administration.
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.
Cutuli
Debora
D
IRCCS Santa Lucia Foundation, Rome, Italy.
Foti
Francesca
F
Mandolesi
Laura
L
De Bartolo
Paola
P
Gelfo
Francesca
F
Federico
Francesca
F
Petrosini
Laura
L
D000109:Acetylcholine / Q000172:deficiency*; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal; D001522:Behavior, Animal / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005106:Exploratory Behavior / Q000187:drug effects; D007189:Indans / Q000008:administration & dosage*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009460:Neurologic Examination; D010880:Piperidines / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012691:Serial Learning / Q000187:drug effects
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D054789:Ribosome Inactivating Proteins, Type 1; D000077265:Donepezil; D000076985:Saporins; D000109:Acetylcholine