Along with work involving CB1 agonists, a several studies have been performed to examine the effects of CB1 blockade on reinstatement to ethanol self-administration. Results from this work suggest that treatment with the CB1 antagonist SR prior to the reinstatement session reduces cue-induced relapse (Cippitelli et al., 2005; Economidou et al., 2006; Economidou et al., 2007), and combining sub-threshold doses of SR with either an adenosine A2A or mGluR5 antagonist also reduces ethanol responding in cued relapse sessions (Adams et al., 2010). This latter approach may prove especially useful for clinical applications seeking to circumvent the negative psychiatric side-effects of higher doses of SR. Importantly, SR treatment has no effect on foot-shock-induced relapse suggesting that CB1 receptors are not involved in mediating stress-induced relapse (Economidou et al., 2006; Economidou et al., 2007). Lastly, Cippitelli et al (2008) found that enhancing brain AEA levels with FAAH inhibitors failed to alter either cue- or stress-induced relapse to ethanol-seeking behavior. These results are not surprising given the number of studies reporting increased AEA levels that persist following chronic ethanol. Together the data from
