The region-specific activation of Ca2+/calmodulin dependent protein kinase II and extracellular signal-regulated kinases in hippocampus following chronic alcohol exposure.

Previous studies suggest that hippocampal CA1, CA3, and DG regions may have distinct roles in alcohol dependence. Extracellular signal-regulated kinases (ERKs) and Ca(2+)/calmodulin dependent protein kinase II (CaMKII) have been shown to contribute to the molecular mechanism underlying drug dependence and relapse, and there may be an interaction between the activation of ERKs and CaMKII. However, little is known regarding the mechanisms underlying the effects of alcohol exposure, withdrawal, and relapse, particularly with regard to the interaction between CaMKII and ERK1/2 signaling in hippocampal subregions. In the present study, rats were provided water containing 6% alcohol as their only drinking source. We found that alcohol exerted locomotor stimulant and anxiolytic effects on rats in open field behaviors. Following chronic alcohol exposure, phospho-ERK1/2 was significantly decreased in the DG. Alcohol withdrawal was associated with an increase of phospho-ERK1/2 in the CA1 and DG, while alcohol re-exposure induced a decrease of phospho-ERK1/2 in the CA1, CA3, and DG. The activation of CaMKII (Thr286) correlated with the effects of alcohol on phospho-ERK1/2. Our results indicate that region-specific activation CaMKII-ERK1/2 signaling in the hippocampal CA1 and DG may play an important role in alcohol dependence.