Paradoxically, mice lacking the kappa receptor showed reduced preference and alcohol consumption in TBC paradigms (Kovacs et al., 2005; van Rijn and Whistler, 2009), which contrast with increased reinforcing effects of other drugs of abuse in these mice. Using similar TBC testing, pDyn KO mice showed increased voluntary consumption (Femenia and Manzanares, 2012; Racz et al., 2012) suggesting that the kappa receptor and dynorphins regulate alcohol intake via distinct mechanisms. Alcohol CPP was unchanged (Blednov et al., 2006; Nguyen et al., 2012c; Sperling et al., 2010) or increased (Femenia and Manzanares, 2012) in mice lacking pDyn. The latter observation is in agreement with the TBC data and the reported aversive-like activity of dynorphin peptides. pDyn KO mice otherwise showed normal increase in stress-induced alcohol preference (Racz et al., 2012; Sperling et al., 2010), but developed stronger withdrawal signs after chronic alcohol (Femenia and Manzanares, 2012). As mu receptors therefore, pDyn influences several aspects of responses to alcohol, and future studies will examine whether kappa/Pdyn signaling indeed operates in alcohol abuse.
