The role of delta receptor in reward is debated. Delta KO mice developed a place preference when morphine was paired with the initially non-preferred compartment, but failed to do so when paired to the preferred side of the apparatus (Chefer and Shippenberg, 2009). The authors interpreted this result as a ceiling effect in the biased CPP protocol that was used more than a decrease of rewarding properties of morphine. In another study, using unbiased CPP, delta KO animals did not develop place preference to morphine (Le Merrer et al., 2011). In the same study, mutant mice showed impaired place conditioning to lithium, an aversive stimulus, and showed normal motivation to obtain morphine in a SA paradigm (Le Merrer et al., 2011). Together with a previous study showing intact intra-VTA SA in delta KO mice (David et al., 2008), the data concur to indicate that morphine reward and motivation to obtain the drug are intact in these animals, however drug-context association is impaired. A subsequent study showed that internal or external non-spatial cues (circadian, drug, auditory) predicting drug or food reward
