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

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

Author information

1
Dipartimento di Scienze Farmacologiche e Biomolecolari, Centro di Neurofarmacologia, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, Italy.
2
IRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Experimental Psychopharmacology, Department of Neuroscience, Via Giuseppe La Masa 19, 20156 Milan, Italy.

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.

PMID:
23953174
DOI:
10.1017/S1461145713000916
[Indexed for MEDLINE]
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