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Narita, M. et al.

Narita, Shibasaki, Nagumo, Narita, Yajima, Suzuki,

Implication of cyclin-dependent kinase 5 in the development of psychological dependence on and behavioral sensitization to morphine.

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.[1]

References

Implication of cyclin-dependent kinase 5 in the development of psychological dependence on and behavioral sensitization to morphine. Narita, M., Shibasaki, M., Nagumo, Y., Narita, M., Yajima, Y., Suzuki, T. J. Neurochem. (2005) [Pubmed]

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