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Implication of cyclin-dependent kinase 5 in the development of psychological dependence on and behavioral

Minoru Narita1, Masahiro Shibasaki, Yasuyuki Nagumo

  • 1Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Shinagawa-ku, Tokyo, Japan. narita@hoshi.ac.jp

Journal of Neurochemistry
|June 7, 2005
PubMed

Insights

Cyclin-dependent kinase 5 (cdk5) plays a key role in morphine

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Repeated morphine administration alters brain dynamics.
  • Understanding the molecular mechanisms underlying morphine dependence is crucial.

Purpose of the Study:

  • To investigate the role of cyclin-dependent kinase 5 (cdk5) in morphine-induced brain changes and dependence.
  • To determine if cdk5 inhibition or deficiency affects morphine's rewarding effects and behavioral sensitization.

Main Methods:

  • In vivo repeated morphine treatment in mice.
  • Measurement of phosphorylated-cdk5 levels in the cingulate cortex.
  • Administration of roscovitine (cdk5 inhibitor) via intracerebroventricular injection.
  • Assessment of morphine's rewarding effect and behavioral sensitization in wild-type and cdk5 heterozygous (+/-) knockout mice.

Main Results:

  • Phosphorylated-cdk5 levels increased in the cingulate cortex following morphine treatment.
  • Roscovitine dose-dependently inhibited the morphine-induced rewarding effect.
  • Morphine's rewarding effect and behavioral sensitization were significantly attenuated in cdk5 (+/-) mice.

Conclusions:

  • Cyclin-dependent kinase 5 (cdk5) induction and/or activation are implicated in the development of morphine dependence.
  • Targeting cdk5 may offer a novel therapeutic strategy for managing opioid addiction.

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