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Implication of cyclin‐dependent kinase 5 in the development of psychological dependence on and behavioral sensitization to morphine
Author(s) -
Narita Minoru,
Shibasaki Masahiro,
Nagumo Yasuyuki,
Narita Michiko,
Yajima Yoshinori,
Suzuki Tsutomu
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03136.x
Subject(s) - cyclin dependent kinase 5 , morphine , sensitization , knockout mouse , pharmacology , kinase , behavioral sensitization , neuroscience , psychology , medicine , chemistry , protein kinase a , nucleus accumbens , central nervous system , receptor , biochemistry , cyclin dependent kinase 2
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.