Journal of Molecular Neuroscience

, Volume 40, Issue 3, pp 284–294 | Cite as

Integrin-Linked Kinase Is Involved in Cocaine Sensitization by Regulating PSD-95 and Synapsin I Expression and GluR1 Ser845 Phosphorylation

  • Qiang Chen
  • Xiongzhao Zhu
  • Yu Zhang
  • William C. Wetsel
  • Tong H. Lee
  • Xiuwu Zhang
Article

Abstract

Our recent studies have demonstrated that integrin-linked kinase (ILK) is involved in the induction and maintenance of cocaine behavioral sensitization and chronic cocaine-induced neural plasticity in the nucleus accumbens (NAc) core. In the present study, we used ILK silencing to investigate how ILK may influence cocaine-induced neural plasticity. Adeno-associated virus carrying a small interfering RNA-ILK cassette under the control of an inducible Tet-On system was injected into the NAc core of Sprague–Dawley rats. Induced silencing was established during repeated cocaine injections (sensitization induction period) or between withdrawal days 9 and 22 (sensitization maintenance period). Under both paradigms, established cocaine sensitization under non-silenced conditions was associated with enhanced PSD-95 and synapsin I protein expression as well as enhanced Ser845 phosphorylation of the GluR1 subunit on withdrawal day. Silencing ILK expression under both paradigms prevented or reversed these changes. Importantly, ILK appears to form a complex with PSD-95 and synapsin I because it co-immunoprecipitated with each of these proteins. Together, these data suggest that ILK exerts pleiotropic actions by regulating pre- and postsynaptic neural plasticities within the NAc core in response to repeated cocaine exposure.

Keywords

Integrin-linked kinase Cocaine Behavioral sensitization PSD-95 SiRNA GluR1 Synapsin I Synaptic plasticity 

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Copyright information

© Humana Press 2009

Authors and Affiliations

  • Qiang Chen
    • 1
  • Xiongzhao Zhu
    • 2
  • Yu Zhang
    • 1
  • William C. Wetsel
    • 1
    • 3
    • 4
  • Tong H. Lee
    • 1
  • Xiuwu Zhang
    • 1
  1. 1.Department of Psychiatry and Behavioral SciencesDuke University Medical CenterDurhamUSA
  2. 2.Medical Psychological Research Center, Second XiangYa HospitalCentral South UniversityChangshaChina
  3. 3.Department of NeurobiologyDuke University Medical CenterDurhamUSA
  4. 4.Department of Cell BiologyDuke University Medical CenterDurhamUSA

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