Absence of opiate rewarding effects in mice lacking dopamine D2 receptors

Nature. 1997 Aug 7;388(6642):586-9. doi: 10.1038/41567.


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 opiates and the somatic expression of morphine abstinence have been related to changes in mesolimbic dopaminergic activity that could constitute the neural substrate for opioid addiction. These adaptive responses to repeated morphine administration have been investigated in mice with a genetic disruption of the dopaminergic D2 receptors. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Addictive*
  • Blotting, Northern
  • Disulfides / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Locomotion
  • Mice
  • Morphine / pharmacology*
  • Phenylalanine / analogs & derivatives
  • Phenylalanine / pharmacology
  • Receptors, Dopamine D2 / deficiency
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / physiology*
  • Reward
  • Substance-Related Disorders / metabolism


  • Disulfides
  • Enzyme Inhibitors
  • Receptors, Dopamine D2
  • RB 101
  • Phenylalanine
  • Morphine