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Acetaldehyde sequestration by d-penicillamine prevents ethanol relapse-like drinking in rats: evidence from an operant self-administration paradigm

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Abstract

Rationale

Previous experiments in our laboratory have shown that d-penicillamine (DP) (acetaldehyde sequestering agent) is able to block the increase in ethanol consumption observed after a period of imposed deprivation (the so-called alcohol deprivation effect (ADE)), using a non-operant paradigm in Wistar rats.

Objectives

This study is aimed at investigating the robustness and reproducibility of our previous data using an operant paradigm, which is considered to be a valid and reliable model of human drug consumption, and the ADE, probably the most often used measure of ethanol relapse-drinking behaviour in rats.

Methods

Male Wistar rats with a limited (30-min sessions), intermittent and extended background of ethanol operant self-administration were used. In order to evaluate the efficacy of several DP doses (6.25, 12.5 and 25 mg/kg i.p.) in preventing alcohol relapse, we set up a protocol based on the ADE. In a separate experiment, the effect of DP on spontaneous motor activity of rats was also tested.

Results

A significant ADE was observed in animals treated with saline. DP treatment blocked the increase in ethanol responses following the imposed abstinence period. The higher dose suppressed the ADE and provoked a significant reduction in ethanol consumption with respect to the baseline conditions. Basal motor activity was not altered after DP treatment.

Conclusion

Our positive results with DP, using two different paradigms that evaluate relapse of ethanol drinking, will help to increase the positive predictive value of pre-clinical experiments and offer a solid base to inspire human studies with DP.

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Acknowledgments

This research was supported by the European Foundation for Alcohol Research and the Fondo de Investigación Sanitaria (Red de Trastornos Adictivos, FEDER, 12/0028/0015). LM-P is a recipient of an ‘Atracció de Talent’ grant from Universitat de València.

Conflict of interest

All authors report having no conflict of interest.

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Authors and Affiliations

  1. Departament de Farmàcia i Tecnologia Farmacèutica, Universitat de València, Avda Vicente Andrés Estellés s/n, 46100, Burjassot, Spain

    Lucía Martí-Prats, Teodoro Zornoza, Luis Granero & Ana Polache

  2. Department of Psychobiology, School of Psychology, Campus de Somosaguas, Complutense University of Madrid, 28223, Madrid, Spain

    José Antonio López-Moreno

Authors
  1. Lucía Martí-Prats
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  2. Teodoro Zornoza
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  3. José Antonio López-Moreno
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  4. Luis Granero
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  5. Ana Polache
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Correspondence to Ana Polache.

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Martí-Prats, L., Zornoza, T., López-Moreno, J.A. et al. Acetaldehyde sequestration by d-penicillamine prevents ethanol relapse-like drinking in rats: evidence from an operant self-administration paradigm. Psychopharmacology 232, 3597–3606 (2015). https://doi.org/10.1007/s00213-015-4011-1

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