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Psilocybin prevents reinstatement of alcohol seeking by disrupting the reconsolidation of alcohol-related memories

Psychopharmacology volume 240, pages 1521–1530 (2023)Cite this article

Abstract

Background

For most psychiatric conditions, including alcohol use disorder (AUD), FDA-approved pharmacological treatments are limited and their efficacy is restricted to only certain subgroups of patients. Scientific interest in the potential of psychedelic drugs has dramatically increased because of clinical preliminary evidence of efficacy in treating various psychiatric disorders. One of the most promising compounds belonging to this class of molecules is psilocybin. Here, to elucidate the therapeutic potential and treatment modalities of this drug, we investigated the effect of psilocybin on alcohol drinking and seeking in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats, a well validated animal model of AUD characterized by excessive drinking and seeking.

Methods

Using male and female msP rats, we tested the effect of psilocybin on home cage voluntary alcohol consumption. We also tested the effect of the drug on the alcohol deprivation effect (ADE) model of relapse and on cue-induced reinstatement of alcohol seeking after a period of abstinence. Finally, we evaluated if psilocybin may disrupt the reconsolidation process of alcohol-related memory.

Results

Psilocybin did not reduce alcohol consumption, nor it prevented increased alcohol drinking after a period of forced abstinence and cue-induced reinstatement of alcohol-seeking. Noteworthy, in a memory retrieval-reconsolidation paradigm, psilocybin markedly attenuated resumption of alcohol seeking.

Conclusions

Altogether these data suggest that, despite psilocybin does not affect alcohol drinking and relapse, it may be highly effective if used to block the reconsolidation process of alcohol-related memories. This opens to the possibility of using this psychedelic drug in clinical settings in which AUD patients undergo procedures to recall the memory of alcohol and are then treated with psilocybin during the memory reconsolidation phase.

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Acknowledgements

We are thankful to Gessica De Santis and Alessandra Vadalà for helping with the experiments and Rina Righi, Agostino Marchi, and Matteo Valzano for animal breeding and expert technical assistance.

Funding

This research was supported by grant ERA-NET Neuron Psi-Alc and by Eva-Maria and Rutger Hetzler Foundation grant Psy-Alc to RC, NIAAA - AA014351 (FW and RC) and NIAAA - AA017447 (MR and RC).

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Authors and Affiliations

  1. School of Pharmacy, Center for Neuroscience, University of Camerino, Camerino, Italy

    F. Benvenuti, D. Colombo, L. Soverchia, N. Cannella, E. Domi & R. Ciccocioppo

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  1. F. Benvenuti
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  2. D. Colombo
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  3. L. Soverchia
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  4. N. Cannella
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  5. E. Domi
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  6. R. Ciccocioppo
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Contributions

Conceptualization, RC; formal analysis, FB, RC; investigation, FB, DC, RC; resources, NC, RC; data curation, FB; writing—original draft preparation, FB, RC; writing—review and editing, FB, RC, NC; funding acquisition, RC. All the authors approved the submitted version and agree to be personally accountable for the author’s own contributions and for ensuring that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and documented in the literature.

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Correspondence to R. Ciccocioppo.

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Benvenuti, F., Colombo, D., Soverchia, L. et al. Psilocybin prevents reinstatement of alcohol seeking by disrupting the reconsolidation of alcohol-related memories. Psychopharmacology 240, 1521–1530 (2023). https://doi.org/10.1007/s00213-023-06384-w

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