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Preventing incubation of drug craving to treat drug relapse: from bench to bedside

Abstract

In 1986, Gawin and Kleber reported a progressive increase in cue-induced drug craving in individuals with cocaine use disorders during prolonged abstinence. After years of controversy, as of 2001, this phenomenon was confirmed in rodent studies using self-administration model, and defined as the incubation of drug craving. The intensification of cue-induced drug craving after withdrawal exposes abstinent individuals to a high risk of relapse, which urged us to develop effective interventions to prevent incubated craving. Substantial achievements have been made in deciphering the neural mechanisms, with potential implications for reducing drug craving and preventing the relapse. The present review discusses promising drug targets that have been well investigated in animal studies, including some neurotransmitters, neuropeptides, neurotrophic factors, and epigenetic markers. We also discuss translational exploitation and challenges in the field of the incubation of drug craving, providing insights into future investigations and highlighting the potential of pharmacological interventions, environment-based interventions, and neuromodulation techniques.

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Fig. 1: Promising drug agents for preventing the incubation of drug craving.
Fig. 2: Incubation of drug craving in humans.

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Acknowledgements

This work was supported in part by the STI2030-Major Projects (no. 2021ZD0200800), and PKU-Baidu Fund (no. 2020BD011). Images in Fig. 1 and Box 2 were created with BioRender.com.

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XXL wrote the draft manuscript. XXL, KY, and TSL constructed the figures and prepared the tables. XL, WZ, YXX, and JS revised the manuscript. LL and YH supervised this review and revised the manuscript. All authors contributed to the article and approved the final version of the manuscript.

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Correspondence to Lin Lu or Ying Han.

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Liu, X., Yuan, K., Lu, T. et al. Preventing incubation of drug craving to treat drug relapse: from bench to bedside. Mol Psychiatry 28, 1415–1429 (2023). https://doi.org/10.1038/s41380-023-01942-2

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