Donepezil reverses nicotine withdrawal-induced deficits in contextual fear conditioning in C57BL/6J mice

Withdrawal from chronic nicotine is associated with cognitive deficits. Therapies that ameliorate cognitive deficits during withdrawal aid in preventing relapse during quit attempts. Withdrawal-induced deficits in contextual learning are associated with nicotinic acetylcholine receptor upregulation. The aim of the present study was to determine if the acetylcholinesterase inhibitor donepezil has the ability to reverse nicotine withdrawal-induced deficits in contextual learning. Results demonstrated that low doses of donepezil, which do not enhance contextual learning or alter locomotor activity/anxiety-related behavior, can reverse nicotine withdrawal-induced deficits in contextual learning. Thus, donepezil may have therapeutic value for ameliorating cognitive deficits associated with nicotine withdrawal and for preventing relapse.