Morphine reward in dopamine-deficient mice.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE

Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.

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

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.

0 (Analgesics, Opioid)
3G6A5W338E (Caffeine)
46627O600J (Levodopa)
63-84-3 (Dihydroxyphenylalanine)
76I7G6D29C (Morphine)
EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
VTD58H1Z2X (Dopamine)

Date Created: 20051213 Date Completed: 20051229 Latest Revision: 20220223

20240104

10.1038/nature04172

16341013