Short-term abstinence from cocaine self-administration, but not passive cocaine infusion, elevates αCaMKII autophosphorylation in the rat nucleus accumbens and medial prefrontal cortex

Int J Neuropsychopharmacol. 2014 Feb;17(2):323-9. doi: 10.1017/S1461145713000916. Epub 2013 Aug 19.


Increases in alpha calcium/calmodulin-dependent protein kinase type II (αCaMKII) activity in the nucleus accumbens shell has been proposed as a core component in the motivation to self-administer cocaine and in priming-induced drug-seeking. Since cocaine withdrawal promotes drug-seeking, we hypothesized that abstinence from cocaine self-administration should enhance αCaMKII as well. We found that short-term abstinence from contingent, but not non-contingent, cocaine i.v. self-administration (2 h/d for 14 d; 0.25 mg/0.1 ml, 6 s infusion) elevates αCaMKII autophosphorylation, but not the kinase expression, in a dynamic, time- and brain region-dependent manner. Increased αCaMKII autophosphorylation in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), but not dorsolateral striatum (dlS), was found 24 h, but not immediately, after the last cocaine self-administration session. Notably, in the mPFC, but not NAc and dlS, αCaMKII autophosphorylation was still enhanced 7 d later. The persistent enhancement in the mPFC of abstinent rats may represent a previously unappreciated contribution to initial incubation of cocaine-seeking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Addictive / enzymology*
  • Behavior, Addictive / psychology
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Cocaine / administration & dosage*
  • Cocaine / adverse effects
  • Infusions, Intravenous
  • Male
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / enzymology*
  • Phosphorylation / drug effects
  • Phosphorylation / physiology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / enzymology*
  • Rats
  • Rats, Sprague-Dawley
  • Self Administration
  • Substance Withdrawal Syndrome / enzymology*
  • Substance Withdrawal Syndrome / psychology
  • Time Factors


  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Camk2a protein, rat
  • Cocaine