The majority of excitatory inputs on cortical pyramidal neurons are made on dendritic spines. The contribution of functionally immature spines has been shown to decrease significantly before adolescence begins. This decrease in immature spines is evident in adolescent monkeys, wherein there is also an increase in the AMPA/NMDA ratio (Gonzalez-Burgos et al., 2008). Mature spines have larger postsynaptic densities, containing more AMPA receptors (Harris et al., 1992); whereas, immature spines have smaller post synaptic densities, containing NMDA receptors but few AMPA receptors (Ganeshina et al., 2004). Ethanol acts by blocking NMDA receptors and activating GABAA receptors. Studies that explore the withdrawal effects from chronic alcohol exposure find hyperactivation of the NMDA receptors due to the lack of alcohol present (Hendricson et al., 2007). Other studies find that chronic alcohol exposure in vitro can result in regionally specific up-regulation of NR1/NR2A expression (Snell et al., 1996) while chronic alcohol exposure in vivo results in an increase in the number of binding sites for MK-801 ( Gulya et al., 1991). Therefore, the AMPA/NMDA ratio could be affected by ethanol through an increase in NMDA receptor presence or binding.
