Acute cocaine increases phosphorylation of CaMKII and GluA1 in the dorsolateral striatum of drug naïve rats, but not cocaine-experienced rats

Neurosci Lett. 2013 Mar 14:537:71-6. doi: 10.1016/j.neulet.2013.01.017. Epub 2013 Jan 24.


Transport of GluA1-containing AMPA glutamate receptors to synapses in the nucleus accumbens, a process that involves phosphorylation of key serine residues by CaMKII, is associated with the reinstatement of cocaine-seeking behavior. A growing body of evidence indicates that the dorsal striatum contributes to aspects of cocaine addiction. However, the potential role of CaMKII-mediated phosphorylation of GluA1 subunits in the dorsolateral (DL) striatum during cocaine reinstatement has not been examined. In this study, rats were trained to self-administer cocaine and were partnered with saline-yoked rats that received injections of saline. Following extinction, each pair of rats received either a systemic priming injection of cocaine (10mg/kg, i.p.) or saline. As expected, cocaine-experienced rats displayed robust reinstatement of cocaine seeking in response to a challenge injection, whereas yoked saline controls did not. The DL striatum was dissected immediately following the reinstatement test session. Results from Western blotting experiments showed increased pGluA1-ser831 and pCaMKII-thr286 in the DL striatum of saline-yoked rats given an acute injection of cocaine. This effect was absent in cocaine-experienced rats that received a saline injection, and no changes were observed following a priming injection of cocaine in cocaine-experienced rats. These results indicate that acute exposure to cocaine in drug naïve rats increased CaMKII-mediated phosphorylation of GluA1-containing AMPA receptors in the DL striatum, an effect that was not observed during cocaine priming-induced reinstatement of drug seeking. It is possible; therefore, that increased phosphorylation of CaMKII and GluA1 following acute cocaine is a compensatory mechanism in the DL striatum.

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Cocaine / pharmacology*
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Drug-Seeking Behavior*
  • Male
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism*
  • Self Administration


  • Receptors, AMPA
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Cocaine
  • glutamate receptor ionotropic, AMPA 1