Given the discrepancies between studies examining the interaction of acute ethanol administration and EC signaling, there is clearly much debate as to the role of the EC system in mediating the intoxicating effects of ethanol. However, several variables that differ in the aforementioned studies may explain the contrasting datasets and may provide future avenues of research. It seems probable that ethanol’s effect on the EC system varies greatly based upon brain the region in question. In support of this hypothesis, the results from Rubio et al (2007) demonstrate that short-term ethanol consumption produced a complex pattern of alterations in the levels of six different ECs that varied substantially by brain region. Additionally, because the EC system mediates retrograde signaling at both glutamatergic and GABAergic synapses there is more biochemical complexity than in most classical neurotransmitter systems. The contrast between the effects of ethanol observed at hippocampal glutamate synapses (Basavarajappa et al., 2008) and at GABAergic synapses (Clarke and Adermark, 2010; Kelm et al., 2008; Roberto et al., 2010) are examples of this complexity. Lastly, the state of the system under
