title: Short-term abstinence from cocaine self-administration, but not passive cocaine infusion, elevates αCaMKII autophosphorylation in the rat nucleus accumbens and medial prefrontal cortex.
abstract: 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.
authors: Dipartimento di Scienze Farmacologiche e Biomolecolari, Centro di Neurofarmacologia, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors: Lucia
authors: L
authors: Caffino
authors: IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Experimental Psychopharmacology, Department of Neuroscience, Via Giuseppe La Masa 19, 20156 Milan, Italy.
authors: Chiara
authors: C
authors: Cassina
authors: Dipartimento di Scienze Farmacologiche e Biomolecolari, Centro di Neurofarmacologia, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors: Giuseppe
authors: G
authors: Giannotti
authors: IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Experimental Psychopharmacology, Department of Neuroscience, Via Giuseppe La Masa 19, 20156 Milan, Italy.
authors: Alessandro
authors: A
authors: Orrù
authors: IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Experimental Psychopharmacology, Department of Neuroscience, Via Giuseppe La Masa 19, 20156 Milan, Italy.
authors: Federico
authors: F
authors: Moro
authors: IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Experimental Psychopharmacology, Department of Neuroscience, Via Giuseppe La Masa 19, 20156 Milan, Italy.
authors: Angelo
authors: A
authors: Di Clemente
authors: Dipartimento di Scienze Farmacologiche e Biomolecolari, Centro di Neurofarmacologia, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors: Giorgio
authors: G
authors: Racagni
authors: Dipartimento di Scienze Farmacologiche e Biomolecolari, Centro di Neurofarmacologia, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
authors: Fabio
authors: F
authors: Fumagalli
authors: IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Experimental Psychopharmacology, Department of Neuroscience, Via Giuseppe La Masa 19, 20156 Milan, Italy.
authors: Luigi
authors: L
authors: Cervo
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000201:enzymology* / Q000523:psychology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000201:enzymology* / Q000523:psychology; D013997:Time Factors
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C517675:Camk2a protein, rat; D003042:Cocaine