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Involvement of nucleus accumbens dopamine D1 receptors in ethanol drinking, ethanol-induced conditioned place preference, and ethanol-induced psychomotor sensitization in mice

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Abstract

Rationale

Dopamine D1 receptor (D1R) signaling has been associated to ethanol consumption and reward in laboratory animals.

Objectives

Here, we hypothesize that this receptor, which is located within the nucleus accumbens (NAc) neurons, modulates alcohol reward mechanisms.

Methods

To test this hypothesis, we measured alcohol consumption and ethanol-induced psychomotor sensitization and conditioned place preference (CPP) in mice that received bilateral microinjections of small interference RNA (siRNA)-expressing lentiviral vectors (LV-siD1R) producing D1R knock-down. The other group received control (LV-Mock) viral vectors into the NAc.

Results

There were no differences in the total fluid consumed and also no differences in the amount of ethanol consumed between groups prior to surgery. However, after surgery, the LV-siD1R group consumed less ethanol than the control group. This difference was not associated to taste neophobia. In addition, results have shown that down-regulation of endogenous D1R using viral-mediated siRNA in the NAc significantly decreased ethanol-induced behavioral sensitization as well as acquisition, but not expression, of ethanol-induced place preference.

Conclusions

We conclude that decreased D1R expression into the NAc led to reduced ethanol rewarding properties, thereby leading to lower voluntary ethanol consumption. Together, these findings demonstrate that the D1 receptor pathway within the NAc controls ethanol reward and intake.

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Abbreviations

CPP:

Conditioned place preference

D1R:

Dopamine D1 receptor

GPCR:

G protein-coupled receptors

EtOH:

Ethanol

LV:

Lentiviral vector

NAc:

Nucleus accumbens

siRNA:

Small interference RNA

VTA:

Ventral tegmental area

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Acknowledgments

This work was supported by a grant from the United Arab Emirates University (AB) and by grants from the Swiss National Science Foundation 3100-059350 and 3100AO-100686 (JLD).

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The authors have no financial interests that might be perceived to influence the results or the discussion reported in this article.

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  1. Department of Anatomy, Faculty of Medicine & Health Sciences, United Arab Emirates University, Tawam Medical Campus, PO Box 17666, Al Ain, United Arab Emirates

    Amine Bahi

  2. Division of Biochemistry, Department of Medicine, University of Fribourg, Fribourg, Switzerland

    Jean-Luc Dreyer

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Correspondence to Amine Bahi.

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Bahi, A., Dreyer, JL. Involvement of nucleus accumbens dopamine D1 receptors in ethanol drinking, ethanol-induced conditioned place preference, and ethanol-induced psychomotor sensitization in mice. Psychopharmacology 222, 141–153 (2012). https://doi.org/10.1007/s00213-011-2630-8

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