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Effects of cannabinoid CB1 receptor antagonist rimonabant in consolidation and reconsolidation of methamphetamine reward memory in mice

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Abstract

Rationale

Previous studies have shown that cannabinoid CB1 receptors play an important role in specific aspects of learning and memory, yet there has been no systematic study focusing on the involvement of cannabinoid CB1 receptors in methamphetamine-related reward memory.

Objectives

The purpose of this study was to examine whether rimonabant, a cannabinoid CB1 receptor antagonist, would disrupt the consolidation and reconsolidation of methamphetamine-related reward memory, using conditioned place preference paradigm (CPP).

Materials and methods

Separate groups of male Kunming mice were trained to acquire methamphetamine CPP. Vehicle or rimonabant (1 mg/kg or 3 mg/kg, i.p.) was given at different time points: immediately after each CPP training session (consolidation), 30 min before the reactivation of CPP (retrieval), or immediately after the reactivation of CPP (reconsolidation). Methamphetamine CPP was retested 24 h and 1 and 2 weeks after rimonabant administration.

Results

Rimonabant at doses of 1 and 3 mg/kg significantly inhibited the consolidation of methamphetamine CPP. Only high-dose rimonabant (3 mg/kg) disrupted the retrieval and reconsolidation of methamphetamine CPP. Rimonabant had no effect on methamphetamine CPP in the absence of methamphetamine CPP reactivation.

Conclusions

Our findings suggest that cannabinoid CB1 receptors play a major role in methamphetamine reward memory, and cannabinoid CB1 receptor antagonists may be a potential pharmacotherapy to manage relapse associated with drug-reward-related memory.

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Acknowledgments

This work was supported in part by the National Basic Research Program of China (Nos. 2007CB512302 and 2009CB522004), the National High Technology Research and Development Program of China (863 Program, 2006AA02Z4D1), and the Natural Science Foundation of China (Nos. 30670713 and 30725016).

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Authors and Affiliations

  1. Insititute of Mental Health and Hebei Brain Ageing and Cognitive Neuroscience Laboratory, Hebei Medical University, Shijiazhuang, 050031, China

    Lu-lu Yu & Xue-yi Wang

  2. National Institute on Drug Dependence, Peking University, 38 Xueyuan Road, Beijing, China

    Mei Zhao, Yu Liu, Yan-qin Li, Fang-qiong Li, Xiaoyi Wang, Yan-xue Xue & Lin Lu

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  1. Lu-lu Yu
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  2. Xue-yi Wang
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Correspondence to Xue-yi Wang or Lin Lu.

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Yu, Ll., Wang, Xy., Zhao, M. et al. Effects of cannabinoid CB1 receptor antagonist rimonabant in consolidation and reconsolidation of methamphetamine reward memory in mice. Psychopharmacology 204, 203–211 (2009). https://doi.org/10.1007/s00213-008-1450-y

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