A likely cause of the reduced CB1 expression found by these studies is an enhancement of EC concentrations induced by chronic ethanol. The first data to support this hypothesis came from experiments performed in cultured cells where it was observed that chronic incubation with intoxicating concentrations of ethanol enhanced both AEA and 2-AG content (Basavarajappa and Hungund, 1999a; Basavarajappa et al., 2000). These authors posited that the enhanced EC levels were due to activation of PLA2 by chronic ethanol thereby increasing EC synthesis (Basavarajappa et al., 1997; Hungund et al., 2002). Other labs have made similar observations following chronic treatment. In rats forced to consume ethanol (7.2%) in a liquid diet, tissue content of AEA was increased in the limbic forebrain, and interestingly, AEA levels were reduced in the midbrain (González et al., 2002), amygdala, and striatum (Rubio et al., 2008). Mitrirattanakul et al (2007) reported that rats made ethanol dependent using a chronic intermittent ethanol regimen displayed increased levels of AEA and 2-AG in the hippocampus that persisted 40 days into withdrawal. Additionally, mice treated with ethanol vapor for
