Cognitive Enhancer Donepezil Attenuates Heroin-Seeking Behavior Induced by Cues in Rats

作者：Disen Mei, Fangmin Wang, Bo Yuan, Miaojun Lai, Yiying Zhou, Wei Cui, Huifen Liu, Wenhua Zhou · 发表于：Journal of Integrative Neuroscience · 年份：2023 · DOI：10.31083/j.jin2203076 · 被引用次数：12 · 研究领域：Neurotransmitter Receptor Influence on Behavior、Nicotinic Acetylcholine Receptors Study、Memory and Neural Mechanisms

PURPOSE: Opioid use disorder is a significant global problem. Chronic heroin use is associated with impairment of cognitive function and conscious control ability. The cholinergic system can be disrupted following heroin administration, indicating that activation of the cholinergic system may prevent chronic heroin misuse. Donepezil as an inhibitor of cholinesterase has been reported to clinically improve cognition and attention. In this study, the inhibition of heroin self-administration and heroin-seeking behaviours by donepezil were evaluated in rats. METHODS: Rats were trained to self-administer heroin every four hours for 14 consecutive days under a fixed ratio 1 (FR1) reinforcement schedule, then underwent withdrawal for two weeks. A progressive ratio schedule was then used to evaluate the relative motivational value of heroin reinforcement. After withdrawal, a conditioned cue was introduced for the reinstatement of heroin-seeking behaviour. Donepezil (0.3-3 mg/kg, i.p.) was used during both the FR1 heroin self-administration and progressive ratio schedules. Immunohistochemistry was used to investigate the mechanism of action of donepezil in the rat brain. RESULTS: Pre-treatment with high dose donepezil (3 mg/kg) but not low doses (0.3-1 mg/kg) significantly inhibited heroin self-administration under the FR1 schedule. Donepezil decreased motivation values under the progressive ratio schedule in a dose-dependent manner. All doses of donepezil (1-3 mg/kg) decreased the re...