Early ethanol exposure and vinpocetine treatment alter learning- and memory-related proteins in the rat hippocampus and prefrontal cortex

This study investigates the effects of early exposure to ethanol on cognitive function and neural plasticity-related proteins in the rat brain. Sprague-Dawley rats were administered 12% ethanol solution (4g/kg/day i.p.) or saline from P4 to P9. Vinpocetine, a phosphodiesterase type 1 inhibitor, was tested to determine whether it could reverse any changes induced by early ethanol exposure. Hence, from P25 to P31, ethanol-exposed male rats were injected with vinpocetine (20mg/kg/day i.p.) or vehicle (DMSO) prior to undergoing behavioral testing in the open field and Morris water maze (MWM) tests. Ethanol exposure did not adversely affect spatial memory in the MWM. A key finding in this study was a significant ethanol-induced change in the function of the phosphorylated extracellular signal-related kinase (P-ERK) signaling pathway in the prefrontal cortex (PFC) and dorsal hippocampus (DH) of rats that did not display overt behavioral deficits. The P-ERK/ERK ratio was decreased in the PFC and increased in the DH of ethanol-exposed rats compared with controls. Rats that received vinpocetine in addition to ethanol did not display any behavioral changes but did show alterations in neural plasticity-related proteins. Mitogen-activated protein kinase phosphatase was increased, whereas brain-derived neurotrophic factor was decreased, in the PFC of vinpocetine-treated ethanol-exposed rats, and phosphorylated-glycogen synthase kinase and synaptophysin were increased in the DH of these rats. This study provides insight into the long-term effects of early ethanol exposure and its interaction with vinpocetine in the rat brain. (c) 2016 Wiley Periodicals, Inc.