Cue-induced reinstatement of alcohol-seeking behavior is associated with increased CaMKII T286 phosphorylation in the reward pathway of mice.

Autor: Salling MC; Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Thurston-Bowles Building; CB #7178, Chapel Hill, NC 27599, United States., Hodge CJ; Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston-Bowles Building; CB #7178, Chapel Hill, NC 27599, United States., Psilos KE; Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston-Bowles Building; CB #7178, Chapel Hill, NC 27599, United States., Eastman VR; Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston-Bowles Building; CB #7178, Chapel Hill, NC 27599, United States., Faccidomo SP; Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston-Bowles Building; CB #7178, Chapel Hill, NC 27599, United States., Hodge CW; Department of Psychiatry, University of North Carolina at Chapel Hill, Thurston-Bowles Building; CB #7178, Chapel Hill, NC 27599, United States; Department of Pharmacology, University of North Carolina at Chapel Hill, Thurston-Bowles Building; CB #7178, Chapel Hill, NC 27599, United States; Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston-Bowles Building; CB #7178, Chapel Hill, NC 27599, United States; Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Thurston-Bowles Building; CB #7178, Chapel Hill, NC 27599, United States. Electronic address: chodge@med.unc.edu.
Jazyk: angličtina
Zdroj: Pharmacology, biochemistry, and behavior [Pharmacol Biochem Behav] 2017 Dec; Vol. 163, pp. 20-29. Date of Electronic Publication: 2017 Oct 31.
DOI: 10.1016/j.pbb.2017.10.011
Abstrakt: Cue-induced reinstatement of alcohol-seeking is a hallmark behavioral pathology of addiction. Evidence suggests that reinstatement (e.g., relapse), may be regulated by cell signaling systems that underlie neuroplasticity. A variety of plasticity events require activation of calcium calmodulin-dependent protein kinase II (CaMKII) in components of the reward pathway, such as the nucleus accumbens and amygdala. We sought to determine if cue-induced reinstatement of alcohol-seeking behavior is associated with changes in the activation state (e.g., phosphorylation) of CaMKII-T286. Male C57BL/6J mice (n=14) were trained to lever press on a fixed-ratio-4 schedule of sweetened alcohol (2% sucrose+9% EtOH) reinforcement. After 14-d of extinction (no cues or reinforcers), mice underwent a response-contingent reinstatement (n=7) vs. an additional day of extinction (n=7). Brains were removed immediately after the test and processed for evaluation of pCaMKII-T286 immunoreactivity (IR). Number of pCaMKII-T286 positive cells/mm 2 was quantified from coronal brain sections using Bioquant Image Analysis software. Mice emitted significantly more responses on the alcohol vs. the inactive lever throughout the baseline phase with average alcohol intake of 1.1±0.03g/kg/1-h. During extinction, responses on the alcohol lever decreased to inactive lever levels by day 7. Significant cue-induced reinstatement of alcohol-seeking was observed during a single test with no effects on the inactive lever. Reinstatement was associated with increased pCaMKII-T286 IR specifically in amygdala (LA and BLA), nucleus accumbens (AcbSh), lateral septum, mediodorsal thalamus, and piriform cortex as compared to extinction control. Brain regions showing no change included the dorsal striatum, medial septum, cingulate cortex, habenula, paraventricular thalamus, and ventral hypothalamus. These results show response contingent cue-induced reinstatement of alcohol-seeking behavior is associated with selective increases in pCaMKII-T286 in specific reward- and memory-related brain regions of male C57BL/6J mice. Primary molecular mechanisms of associative learning and memory may regulate relapse in alcohol addiction.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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