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Absence of opiate rewarding effects in mice lacking dopamine D2 receptors

Nature volume 388, pages 586–589 (1997)Cite this article

Abstract

Dopamine receptors have been implicated in the behavioural response to drugs of abuse. These responses are mediated particularly by the mesolimbic dopaminergic pathway arising in the ventral tegmental area and projecting to the limbic system. The rewarding properties of opiates1 and the somatic expression of morphine abstinence2 have been related to changes in mesolimbic dopaminergic activity that could constitute the neural substrate for opioid addiction3. These adaptive responses to repeated morphine administration have been investigated in mice with a genetic disruption of the dopaminergic D2 receptors4. Although the behavioural expression of morphine withdrawal was unchanged in these mice, a total suppression of morphine rewarding properties was observed in a place-preference test. This effect is specific to the drug, as mice lacking D2 receptors behaved the same as wild-type mice when food is used as reward. We conclude that the D2 receptor plays a crucial role in the motivational component of drug addiction.

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Figure 1: D2R-null mice preserve exploratory activity and locomotor response to morphine treatment.
Figure 2: Lack of morphine-induced place preference in D2R-null mice.
Figure 3: µ-Opioid receptor expression in D2R-null mice.
Figure 4: Analysis of morphine-induced physical dependence.

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Acknowledgements

We acknowledge B. Kieffer for the gift of µ-opioid cDNA. A.S. and O.V. were recipient of fellowships from the European Community and T.A.S. from the Centre Nationale de la Recherche Scientifique (CNRS). This work was supported by funds from the Ministère de la Recherche to R.M., from the Association pour la Recherche sur le Cancer to R.M. and to E.B., and from the Institut Nationale de la Santé et de la Recherche Médicale, CNRS et Centre Hospitalier Universitaire Regional to E.B.

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  1. Dpartement de Pharmacochimie Molculaire et Structurale, INSERM U266, URA D1500 CNRS, Universit Ren Descartes, 75270, Paris, France

    Rafael Maldonado, Olga Valverde & Bernard P. Roques

  2. Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM/CNRS/ULP, BP 163, C.U. de Strasbourg, 67404, Illkirch, France

    Adolfo Saiardi, Tarek A. Samad & Emiliana Borrelli

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  1. Rafael Maldonado
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Correspondence to Emiliana Borrelli.

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Maldonado, R., Saiardi, A., Valverde, O. et al. Absence of opiate rewarding effects in mice lacking dopamine D2 receptors. Nature 388, 586–589 (1997). https://doi.org/10.1038/41567

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