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Psychopharmacology

, Volume 205, Issue 2, pp 327–335 | Cite as

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

  • Valentina SabinoEmail author
  • Pietro Cottone
  • Yu Zhao
  • Luca Steardo
  • George F. Koob
  • Eric P. ZorrillaEmail author
Original Investigation

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.

Keywords

Ethanol Addiction Rat Alcoholism Treatment 

Notes

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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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Valentina Sabino
    • 1
    • 3
    Email author
  • Pietro Cottone
    • 1
    • 3
  • Yu Zhao
    • 2
    • 3
  • Luca Steardo
    • 4
  • George F. Koob
    • 2
  • Eric P. Zorrilla
    • 2
    • 3
    Email author
  1. 1.Laboratory of Addictive Disorders, Department of Pharmacology and Experimental TherapeuticsBoston University School of MedicineBostonUSA
  2. 2.Committee on the Neurobiology of Addictive DisordersThe Scripps Research InstituteLa JollaUSA
  3. 3.Harold L. Dorris Neurological Research InstituteThe Scripps Research InstituteLa JollaUSA
  4. 4.Department of Human Physiology and PharmacologyLa Sapienza UniversityRomeItaly

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