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Selective reduction of alcohol drinking in Sardinian alcohol-preferring rats by a sigma-1 receptor antagonist

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Abstract

Rationale and objectives

Sigma receptors have been implicated in appetitive effects of psychostimulants and in high levels of ethanol intake. This study tested the hypothesis that the sigma-1 receptor subtype (Sig-1R) may modulate ethanol intake.

Material and methods

The effects of acute and repeated treatment with the potent, selective Sig-1R antagonist NE-100 on ethanol intake (10%) were studied in adult, male Sardinian alcohol-preferring (sP) rats, a model of genetic predisposition to high ethanol drinking. To assess the specificity of action, the acute effects of NE-100 on intake of an equally preferred sucrose solution and of a higher concentration of ethanol that sP rats did not prefer over water (28%), were determined. Finally, the ability of NE-100 administration to prevent the increased ethanol intake that occurs after deprivation was evaluated.

Results

Acute treatment with NE-100 dose-dependently (10–30 mg/kg) reduced 1- and 3-h intake of 10% ethanol solution in sP rats, while increasing concurrent water intake and not affecting food intake. NE-100 (17.8–30 mg/kg) comparably reduced intake of the 28% ethanol solution, while not suppressing 1.25% sucrose solution intake, suggesting selectivity of action against ethanol intake. Acute NE-100 (30 mg/kg) also prevented an increase in ethanol intake after a 7-day deprivation period. Repeated, daily NE-100 (30 mg/kg) treatment continued to reduce 24-h ethanol intake across 7 days of administration, with some, but incomplete, tolerance, evident by day 6.

Conclusions

The results implicate the Sig-1R system in alcohol drinking, identifying a potential therapeutic target for the treatment of alcohol use disorders.

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Acknowledgements

Research was supported by grants from the National Institute on Alcohol Abuse and Alcoholism (5K99AA016731-02, 2P60AA006420-25, and 5R01AA012602-09) and by the Pearson Center for Alcoholism and Addiction Research. This is manuscript number 19878 from The Scripps Research Institute. The authors thank Taisho Pharmaceuticals for the gift of NE-100, the excellent technical assistance of Maury Cole, Molly Brennan, Jeanette Helfers and Robert Lintz, and the editorial assistance of Mike Arends.

Disclosure/conflicts of interest

The authors declare no conflicts of interest.

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Author notes

  1. Valentina Sabino & Pietro Cottone

    Present address: Laboratory of Addictive Disorders, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, 72 East Concord Street, Boston, MA, 02118, USA

Authors and Affiliations

  1. Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA, 92037, USA

    Yu Zhao, George F. Koob & Eric P. Zorrilla

  2. Harold L. Dorris Neurological Research Institute, The Scripps Research Institute, La Jolla, CA, 92037, USA

    Valentina Sabino, Pietro Cottone, Yu Zhao & Eric P. Zorrilla

  3. Department of Human Physiology and Pharmacology, La Sapienza University, Rome, Italy

    Luca Steardo

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  1. Valentina Sabino
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  2. Pietro Cottone
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  3. Yu Zhao
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  4. Luca Steardo
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Corresponding authors

Correspondence to Valentina Sabino or Eric P. Zorrilla.

Additional information

Valentina Sabino and Pietro Cottone contributed equally to this work.

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Sabino, V., Cottone, P., Zhao, Y. et al. Selective reduction of alcohol drinking in Sardinian alcohol-preferring rats by a sigma-1 receptor antagonist. Psychopharmacology 205, 327–335 (2009). https://doi.org/10.1007/s00213-009-1548-x

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  • DOI: https://doi.org/10.1007/s00213-009-1548-x

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