Abstract
In the present study, we investigated the role of cyclin-dependent kinase 5 (cdk5) in the brain dynamics changed by repeated in vivo treatment with morphine. The level of phosphorylated-cdk5 was significantly increased in the cingulate cortex of mice showing the morphine-induced rewarding effect. Under these conditions, roscovitine, a cdk5 inhibitor, given intracerebroventricularly (i.c.v.) caused a dose-dependent and significant inhibition of the morphine-induced rewarding effect. In addition, the dose-response effect of the morphine-induced rewarding effect was dramatically attenuated in cdk5 heterozygous (+/-) knockout mice. Furthermore, the development of behavioral sensitization by intermittent administration of morphine was virtually abolished in cdk5 (+/-) mice. These findings suggest that the induction and/or activation of cdk5 are implicated in the development of psychological dependence on morphine.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Behavior, Animal / drug effects
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Behavior, Animal / physiology
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Brain Chemistry / drug effects*
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Brain Chemistry / genetics
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Cyclin-Dependent Kinase 5
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Cyclin-Dependent Kinases / drug effects
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Cyclin-Dependent Kinases / genetics
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Cyclin-Dependent Kinases / physiology*
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Drug Administration Schedule
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Enzyme Inhibitors / pharmacology
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Female
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Gyrus Cinguli / drug effects*
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Gyrus Cinguli / enzymology
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Gyrus Cinguli / physiopathology
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Male
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Mice
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Mice, Knockout
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Morphine / pharmacology*
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Morphine Dependence / enzymology*
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Morphine Dependence / genetics
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Narcotics / pharmacology
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / genetics
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Phosphorylation / drug effects
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Purines / pharmacology
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Reward
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Roscovitine
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Up-Regulation / drug effects
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Up-Regulation / genetics
Substances
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Enzyme Inhibitors
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Narcotics
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Purines
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Roscovitine
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Morphine
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Cyclin-Dependent Kinase 5
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Cdk5 protein, mouse
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Cyclin-Dependent Kinases