al. 2005). Factors that reduce neurogenesis increase depression-like behavior (Johnson et al. 2006). Activation of NF-κB is necessary for stress induced inhibition of neurogenesis and induction of depression-like behavior (Koo and Duman 2008) as well as social defeat models of depression (Christoffel et al. 2011). Further, antidepressant efficacy in rodent behavioral models requires hippocampal neurogenesis (Santarelli et al. 2003). In animal studies, endotoxin induced increases in innate immune genes reduce neurogenesis and increase depression-like behavior (Kelley 2011). TLRs are necessary components of both ethanol neurotoxicity (Alfonso-Loeches et al. 2010) and innate immune induced depressive behavior and reduction of neurogenesis (Kelley 2011). TLR, glutamate hyperexcitability and endogenous TLR agonists lead to persistent increases in brain hyperexcitability (Maroso et al. 2010). We have found that chronic ethanol increases brain innate immune genes, reduces brain neurogenesis and increases depression-like behavior (Stevenson et al. 2009) (Fig. 4.) Ethanol induced loss of neurogenesis paralleled the onset of depression-like behavior with both reversed by anti-depressant treatment (Stevenson et al. 2009). Similarly stress induced IL-1β reduces neurogenesis causing depression like behavior (Koo and Duman 2008). Thus, neurogenesis reflects mood, with reduced neurogenesis associated with innate immune gene induction, drug induced negative affect and depression-like behavior. Interestingly, recovery
