Neural plasticity and addiction: integrin-linked kinase and cocaine behavioral sensitization.
Behavioral sensitization of psychostimulants was accompanied by alterations in a variety of biochemical molecules in different brain regions. However, which change is actually related to drug-produced sensitization lacks of accurate clarification. In this study, we investigated the role of integrin-linked kinase (ILK) in both the induction and expression of cocaine sensitization. Conditional inhibition of ILK expression was established in the nucleus accumbens (NAc) core by microinjecting recombinant adeno-associated virus-carrying, tetracycline-on-regulated small interfering RNA which reversed the chronic cocaine-induced psychomotor sensitization, as well as the changes in protein kinase B Ser473 phosphorylation, dendritic density, and dendritic spine numbers locally. Importantly, the reversed psychomotor sensitization did not recover after cessation of the silencing for 8 days. We also demonstrated that inhibition of ILK expression pre- and during-chronic cocaine treatments blocked the induction of cocaine psychomotor sensitization and abolished the stimulant effect of cocaine on ILK expression. In contrast, inhibition of ILK expression in the NAc core has no significant effect on cocaine-induced stereotypical behaviors. This concludes that ILK is involved in cocaine sensitization with the earlier induction and later expression functioning as a kinase to regulate protein kinase B Ser473 phosphorylation and a scaffolding protein to regulate the reorganization of the NAc spine morphology.
Chen
Qiang
Q
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27710, USA.
Xiong
Xueying
X
Lee
Tong H
TH
Liu
Yingmiao
Y
Wetsel
William C
WC
Zhang
Xiuwu
X
D000818:Animals; D016739:Behavior, Addictive / Q000378:metabolism* / Q000503:physiopathology; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D003712:Dendrites / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D000099200:Scaffold Protein ILK
D003042:Cocaine; D018765:Dopamine Uptake Inhibitors; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D000099200:Scaffold Protein ILK