Absence of opiate rewarding effects in mice lacking dopamine D2 receptors

Rafael Maldonado, Adolfo Saiardi, Olga Valverde, Tarek A. Samad, Bernard P. Roques and Emiliana Borrelli ()
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Rafael Maldonado: Dpartement de Pharmacochimie Molculaire et Structurale, INSERM U266, URA D1500 CNRS, Universit Ren Descartes
Adolfo Saiardi: Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM/CNRS/ULP, BP 163
Olga Valverde: Dpartement de Pharmacochimie Molculaire et Structurale, INSERM U266, URA D1500 CNRS, Universit Ren Descartes
Tarek A. Samad: Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM/CNRS/ULP, BP 163
Bernard P. Roques: Dpartement de Pharmacochimie Molculaire et Structurale, INSERM U266, URA D1500 CNRS, Universit Ren Descartes
Emiliana Borrelli: Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM/CNRS/ULP, BP 163

Nature, 1997, vol. 388, issue 6642, 586-589

Abstract: 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.

Date: 1997
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DOI: 10.1038/41567

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