Morphine self-administration in mu-opioid receptor-deficient mice.
Morphine-induced place preference was demonstrated recently in wild-type mice, whereas this conditioned behaviour was not observed in mu-opioid receptor-deficient mice. In the present study, we investigated locomotor effects of subcutaneously (s.c.) injected morphine as well as intracerebroventricular (i.c.v.) morphine self-administration in mu-opioid receptor-knockout mice. After s.c. morphine injection, locomotor activity significantly increased in wild-type animals. As expected, in the self-administration test the rate of self-administration constantly increased in wild-type mice reflecting reward effects of morphine. This increase was independent of locomotor/motor activity. In contrast, self-administration rates and locomotor/motor activity significantly decreased in the receptor-deficient animals. It was shown that this aversive effect might partly be due to kappa-opioid receptor interaction.
Becker
A
A
Institute of Pharmacology and Toxicology, Faculty of Medicine, Otto-von-Guericke University, Magdeburg, Germany. axel.becker@medizin.uni-magdeburg.de
Grecksch
G
G
Brödemann
R
R
Kraus
J
J
Peters
B
B
Schroeder
H
H
Thiemann
W
W
Loh
H H
HH
Höllt
V
V
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D003342:Corpus Striatum / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism; D007276:Injections, Intraventricular; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D011869:Radioligand Assay; D011897:Random Allocation; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism*; D012646:Self Administration
D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine