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

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