and is critical for neuronal plasticity, including long-term potentiation (Corriveau et al., 1998; Huh et al., 2000; Linda et al., 1999). IL-1 is one of the most prevalent and important cytokines and its actions are regulated by an endogenous antagonist, IL-1rn. Both are released from microglia and glia and act on receptors on neurons and glia (Molina-Holgado et al., 2003; Tsakiri et al., 2008), and elevated levels of IL-1rn interfere with memory consolidation (Spulber et al., 2009). IL-1 also stimulates the release of IL-6 from neurons and glia (Tsakiri et al., 2008). IL-6 acts on neuronal receptors to suppress inhibitory transmission by reducing GABA-A and glycine receptor function (Kawasaki et al., 2008). Deletion of Il1rn produced some of the most pronounced changes in drinking in both tests and it is of interest to note that activation of cannabinoid (CB1 and CB2) receptors mediate release of IL-1rn and that IL-1rn disrupts BDNF-ERK1/2 signaling (Molina-Hidalgo et al, 2003: Spulber et al., 2009). Thus, deletion of Il1rn should reduce some effects of endocannabioids and enhance BDNF signaling. Importantly, treatments that reduce CB1 receptor signaling or enhance BDNF activity reduce alcohol consumption (Wang et al., 2003; Jeanblanc et al., 2009), suggesting mechanisms by which
