Absence of opiate rewarding effects in mice lacking dopamine d2 receptors

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. Access through your institution Buy or subscribe This is a preview of

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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. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Dpartement de Pharmacochimie Molculaire et

Structurale, INSERM U266, URA D1500 CNRS, Universit Ren Descartes, 75270, Paris, France Rafael Maldonado, Olga Valverde & Bernard P. Roques * 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 Authors * Rafael Maldonado View author

publications You can also search for this author inPubMed Google Scholar * Adolfo Saiardi View author publications You can also search for this author inPubMed Google Scholar * Olga Valverde

View author publications You can also search for this author inPubMed Google Scholar * Tarek A. Samad View author publications You can also search for this author inPubMed Google Scholar *

Bernard P. Roques View author publications You can also search for this author inPubMed Google Scholar * Emiliana Borrelli View author publications You can also search for this author

inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Emiliana Borrelli. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation *

Received: 04 November 1996 * Accepted: 09 May 1997 * Issue Date: 07 August 1997 * DOI: https://doi.org/10.1038/41567 SHARE THIS ARTICLE Anyone you share the following link with will be able

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