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. 2014 Oct;128(5):588-93.
doi: 10.1037/bne0000003. Epub 2014 Jun 9.

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

Rachel L Poole  1 , David A Connor  1 , Thomas J Gould  1
Affiliations

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

Rachel L Poole et al. Behav Neurosci. 2014 Oct.

Abstract

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.

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Conflict of interest statement

Disclosure

All authors report no potential conflicts of interest.

Figures

Figure 1
Figure 1
The effects of acute donepezil on fear conditioning (n=11–12 for each dose group). Doses of donepezil between 0.015 and 0.5 mg/kg had no effect on fear conditioning. The highest dose of donepezil tested (1.5 mg/kg) increased baseline, immediate, context, and pre-CS freezing. *Significantly different from Saline. Error bars represent ±SEM.
Figure 2
Figure 2
The effects of acute donepezil on nicotine withdrawal-induced deficits in contextual conditioning (n=8–10 for each dose group). Donepezil reversed deficits in contextual learning induced by withdrawal from chronic nicotine. WCS = withdrawal from chronic saline. WCN = withdrawal from chronic nicotine. *Significantly different from WCS + Saline. Error bars represent ±SEM.
See this image and copyright information in PMC

References

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