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 study may have a large impact on EC signaling. The in vivo studies in the BLA, VTA, and NAc were all conducted in urethane anesthetized animals raising the possibility that the anesthetic used in these studies alters EC signaling itself. Along these lines, the EC system has been implicated in mediating some of the effects of the general anesthetic propofol (Patel et al., 2003), but there are currently no data available as to the effects of urethane on the EC system, making data from the in vivo studies difficult to interpret in light of conflicting results. Additionally, a nascent but growing body of evidence has linked the EC system to the regulation of the sleep/wake cycle (for review see Murillo-Rodriguez et al., 2011). As a consequence, future studies should be sensitive to the possible interactions between the EC system and the state of the organism under study.
