Cocaine facilitates PKC maturation by upregulating its phosphorylation at the activation loop in rat striatal neurons in vivo

Bing Xue, Ming Lei Guo, Dao Zhong Jin, Li Min Mao, John Q. Wang

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Newly synthesized protein kinase C (PKC) undergoes a series of phosphorylation to render a mature form of the enzyme. It is this mature PKC that possesses the catalytic competence to respond to second messengers for activation and downstream signaling. The first and rate-limiting phosphorylation occurs at a threonine residue in the activation loop (AL), which triggers the rest maturation processing of PKC and regulates PKC activity in response to cellular stimulation. Given the fact that PKC is enriched in striatal neurons, we investigated the regulation of PKC phosphorylation at the AL site in the rat striatum by the psychostimulant cocaine in vivo. We found that PKC was phosphorylated at the AL site at a moderate level in the normal rat brain. Acute systemic injection of cocaine increased the PKC-AL phosphorylation in the two striatal structures (caudate putamen and nucleus accumbens). Cocaine also elevated the PKC-AL phosphorylation in the medial prefrontal cortex. The cocaine-stimulated PKC phosphorylation in the striatum is rapid and transient. A reliable increase in PKC phosphorylation was seen 7 min after drug injection, which declined to the normal level by 1 h. This kinetics corresponds to that seen for another striatum-enriched protein kinase, mitogen-activated protein kinase/extracellular signal-regulated kinase, in response to cocaine. This study suggests a new model for exploring the impact of cocaine on protein kinases in striatal neurons. By modifying PKC phosphorylation at the AL site, cocaine is believed to possess the ability to alter the maturation processing of the kinase in striatal neurons in vivo.

Original languageEnglish (US)
Pages (from-to)146-153
Number of pages8
JournalBrain Research
StatePublished - Jan 30 2012


  • Addiction
  • Caudate
  • Dopamine
  • ERK
  • Nucleus accumbens
  • Prefrontal cortex
  • Protein kinase C
  • Stimulant

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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