was Ca2+-dependent. Furthermore, these authors reported that the ethanol-mediated increase in EC levels resulted in reduced pre-synaptic glutamate release. Additional evidence comes from in vivo studies where SR or chronic pre-treatment with the CB1 agonist, WIN 55,212-2 (WIN), reduced the effect of acute ethanol administration to alter the spontaneous firing rate of basolateral amygdala (BLA; Perra et al., 2008) and ventral tegmetal area (VTA; Perra et al., 2005)projection neurons. Similar findings were also obtained from evoked activity in nucleus accumbens (NAc) neurons (Perra et al., 2005). The effect of chronic WIN treatment on the response of VTA neurons to acute ethanol is particularly interesting because it implies that the rewarding properties of ethanol may be reduced following chronic exposure to cannabinoids, and this may be of significance to the high prevalence of comorbidity between AUDs and CUDs discussed previously. Data regarding the role of the EC system in mediating the rewarding properties of ethanol will be discussed in the next section.
