Ingenuity® analysis of the proteins altered by ethanol in the ACB-sh of NP rats indicated a calmodulin network (Fig. 3) involved in calcium signaling and long-term potentiation (LTP) and a G-protein network (Fig. 4) involved in axonal guidance signaling and long-term depression (LTD). The calmodulin-calcium intracellular signaling pathway (Fig. 3) and the G-protein intracellular signaling network (Fig. 4) are composed of proteins that have been primarily up-regulated in the ACB-shell of the NP rat, suggesting ethanol-enhanced synaptic plasticity. The up-regulation of ARP2 actin-related protein (Actr2) and WAS protein family member 1 (Wasf1) are also consistent with an interpretation of ethanol-enhanced synaptic plasticity. Actr2 facilitates neuronal actin remodeling (Soderling et al., 2007), and Wasf1 is involved in linking actin dynamics and synaptic vesicle endocytosis (Shin et al., 2007). The higher protein expression levels of clathrin heavy chain (Cltc) also support ethanol-induced postsynaptic alterations.
