Opposing mu receptor mutants, delta KO mice showed increased alcohol consumption in TBC (Roberts et al., 2001; van Rijn et al., 2010; van Rijn and Whistler, 2009) and oral SA combined with TBC (Roberts et al., 2001) paradigms and their innate anxiety returned to wild-type levels after alcohol SA (Roberts et al., 2001). Given the important role of delta in reducing emotional responses (Filliol et al., 2000), increased alcohol intake in these mutants may reflect a self-medication approach to alleviate high levels of anxiety (for a recent review, see (Chu Sin Chung and Kieffer, in press). Interestingly, pEnk KO animals showed intact rewarding effect of alcohol and a normal pattern of alcohol consumption (Koenig and Olive, 2002), however alcohol drinking was modified in pEnk KO under stressful conditions. The latter observation supports a role for delta/pEnk signaling in regulating emotional responses that may impact on alcohol consumption. β-endorphin may also be involved since alcohol intake was reduced (Racz et al., 2008), unchanged (Hayward et al., 2004) or increased (Grahame et al., 1998; Grisel et al., 1999) in βend KO mice.
