Morphine reward in dopamine-deficient mice

Nature. 2005 Dec 8;438(7069):854-7. doi: 10.1038/nature04172.


Dopamine has been widely implicated as a mediator of many of the behavioural responses to drugs of abuse. To test the hypothesis that dopamine is an essential mediator of various opiate-induced responses, we administered morphine to mice unable to synthesize dopamine. We found that dopamine-deficient mice are unable to mount a normal locomotor response to morphine, but a small dopamine-independent increase in locomotion remains. Dopamine-deficient mice have a rightward shift in the dose-response curve to morphine on the tail-flick test (a pain sensitivity assay), suggesting either a decreased sensitivity to the analgesic effects of morphine and/or basal hyperalgesia. In contrast, dopamine-deficient mice display a robust conditioned place preference for morphine when given either caffeine or l-dihydroxyphenylalanine (a dopamine precursor that restores dopamine throughout the brain) during the testing phases. Together, these data demonstrate that dopamine is a crucial component of morphine-induced locomotion, dopamine may contribute to morphine analgesia, but that dopamine is not required for morphine-induced reward as measured by conditioned place preference.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Caffeine / pharmacology
  • Dihydroxyphenylalanine / pharmacology
  • Dopamine / deficiency*
  • Dopamine / metabolism
  • Dose-Response Relationship, Drug
  • Levodopa / administration & dosage
  • Levodopa / pharmacology
  • Mice
  • Morphine / administration & dosage
  • Morphine / pharmacology*
  • Motor Activity / drug effects*
  • Motor Activity / physiology
  • Pain / physiopathology
  • Pain Threshold / drug effects*
  • Pain Threshold / physiology
  • Reward*
  • Tail / drug effects
  • Tail / physiology
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism


  • Analgesics, Opioid
  • Caffeine
  • Levodopa
  • Dihydroxyphenylalanine
  • Morphine
  • Tyrosine 3-Monooxygenase
  • Dopamine