Acute ethanol administration decreases GAP-43 and phosphorylated-GAP-43 in the rat hippocampus

Acute alcohol ingestion is well known to have deleterious effects on memory and also known to inhibit long-term potentiation, a putative cellular substrate of memory. In this study, we for the first time revealed that growth-associated protein 43 (GAP-43), which is well known as a presynaptic substrate of protein kinase C and one of the major synaptic plasticity-related genes, was down regulated by single ethanol administration (2.5 g/kg, 15% in saline, i.p.) in the rat hippocampus. Using real-time PCR, we confirmed that GAP-43 mRNA level is significantly decreased 2 h after ethanol administration. GAP-43 and p-GAP-43 (Ser41) immunoreactivities in the hippocampus were also reduced 4 h after ethanol administration. Immunohistochemical study showed that the reduction of GAP-43 and p-GAP-43 expression was associated with the perforant and mossy fibers pathways. These results suggest that the reduction of GAP-43 in the hippocampus might be, at least in part, a cause of memory impairment after acute ethanol ingestion.