A number of molecular, biochemical, and behavioral alterations that resemble those previously identified in human and in vitro studies have been identified in G112 mice (Mague et al., 2009). For instance, the presence of the G112 allele results in decreased MOPR mRNA and protein expression. This decrease in receptor expression was also seen using [3H]-DAMGO binding, though there were no alterations in affinity for β-endorphin or exogenous ligands (morphine, DAMGO, or naloxone). Mice with the G112 allele showed only a modest elevation in locomotor activity following acute morphine administration and failed to develop sensitization to repeated, intermittent injections. Similarly, G112 mice had reduced morphine-induced antinociceptive responses, though they showed similar signs of tolerance following repeated treatments. A sex × genotype interaction was found in measures of hedonia: female G112-carriers did not display a preference for morphine-associated environments nor did they demonstrate an aversion to environments associated with naloxone-precipitated withdrawal.
