Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Striatal dysregulation of Cdk5 alters locomotor responses to cocaine, motor learning, and dendritic morphology.

Motor learning and neuro-adaptations to drugs of abuse rely upon neuronal signaling in the striatum. Cyclin-dependent kinase 5 (Cdk5) regulates striatal dopamine neurotransmission and behavioral responses to cocaine. Although the role for Cdk5 in neurodegeneration in the cortex and hippocampus and in hippocampal-dependent learning has been demonstrated, its dysregulation in the striatum has not been examined. Here we show that strong activation of striatal NMDA receptors produced p25, the truncated form of the Cdk5 co-activator p35. Furthermore, inducible overexpression of p25 in the striatum prevented locomotor sensitization to cocaine and attenuated motor coordination and learning. This corresponded with reduced dendritic spine density, increased neuro-inflammation, altered dopamine signaling, and shifted Cdk5 specificity with regard to physiological and aberrant substrates, but no apparent loss of striatal neurons. Thus, dysregulation of Cdk5 dramatically affects striatal-dependent brain function and may be relevant to non-neurodegenerative disorders involving dopamine neurotransmission.

Pubmed ID: 19017804 RIS Download

Mesh terms: Animals | Behavior, Animal | Cocaine | Corpus Striatum | Cyclin-Dependent Kinase 5 | Dendrites | Learning | Locomotion | Mice | Mice, Transgenic | Receptors, N-Methyl-D-Aspartate

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NHLBI NIH HHS, Id: HL077101
  • Agency: NIMH NIH HHS, Id: MH079710-0
  • Agency: NIDA NIH HHS, Id: T32 DA007290
  • Agency: NINDS NIH HHS, Id: R01 NS051874
  • Agency: NIMH NIH HHS, Id: P50 MH074866
  • Agency: NIDA NIH HHS, Id: T32-DA7290
  • Agency: NIMH NIH HHS, Id: R01 MH079710
  • Agency: NINDS NIH HHS, Id: NS051874
  • Agency: NIDA NIH HHS, Id: DA16672
  • Agency: NIDA NIH HHS, Id: P01 DA010044
  • Agency: NIDA NIH HHS, Id: R01 DA016672
  • Agency: Howard Hughes Medical Institute, Id: MH074866
  • Agency: NIMH NIH HHS, Id: DA10044
  • Agency: NIDA NIH HHS, Id: P50 HL077101
  • Agency: NHLBI NIH HHS, Id:

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.