Effect of donepezil on reversal learning in a touch screen-based operant task.
Impairments in reversal learning, which are commonly observed in patients with psychiatric disorders, remain difficult to treat. There is still a debate over the beneficial effects of cholinergic enhancers on improving behavioural flexibility. The objective of this study was to investigate the effect of an acetylcholinesterase inhibitor, donepezil, on the performance of a rodent Probabilistic Reversal Learning task. Lister-Hooded rats were trained to retrieve food rewards by discriminating two computer-generated stimuli in an automated touch screen-based operant task. When a steady performance was achieved, the stimulus-reward rule was reversed. Each rat was given a 30-min training session daily for 24 days and donepezil was administered 30 min before each training session. Systemic treatment with donepezil had no effect on trial accuracy of the two-stimulus discrimination training. However, the donepezil group showed enhanced performance in the reversal learning. Our result showed that treatment with donepezil significantly enhanced Probabilistic Reversal Learning performance in healthy animals. On the basis of this finding, the inhibition of the central acetylcholinesterase would seem to be a potential therapeutic approach to treat behavioural inflexibility.
Chen
Woei-Shin
WS
GSK R&D China, Singapore Research Centre, Singapore. woei-shin.w.chen@gsk.com
Wong
Fong-Kuan
FK
Chapman
Paul F
PF
Pemberton
Darrel J
DJ
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D016287:Computer Peripherals; D003216:Conditioning, Operant / Q000187:drug effects*; D004193:Discrimination Learning / Q000187:drug effects; D000077265:Donepezil; D007189:Indans / Q000494:pharmacology*; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012193:Reversal Learning / Q000187:drug effects*
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil