Morphine reward in dopamine-deficient mice.
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.
Hnasko
Thomas S
TS
Graduate Program in Neurobiology & Behavior, University of Washington, Seattle, Washington 98195, USA.
Sotak
Bethany N
BN
Palmiter
Richard D
RD
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000494:pharmacology; D004298:Dopamine / Q000172:deficiency* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010146:Pain / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D012201:Reward; D013623:Tail / Q000187:drug effects / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D000701:Analgesics, Opioid; D002110:Caffeine; D007980:Levodopa; D004295:Dihydroxyphenylalanine; D009020:Morphine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine