Animal models have also provided some validation of sweet liking as a strong candidate endophenotype for AUD and for addiction phenotypes more broadly [106, 84]. Rats selected for high saccharin intake consumed more ethanol relative to rats selected for low saccharin intake [107], and they exhibit greater ethanol withdrawal [108]. Saccharin consumption also appears to offset alcohol consumption. P rats who voluntarily consume saccharin subsequently drink less ethanol compared to alcohol preferring rats who are not given access to saccharin [109]. This suggests that ethanol and saccharin consumption may have overlapping effects on (genetically-influenced) neurobiological systems involved in reward, such as the opioid, serotonin, and dopamine systems [110]. Consistent with this idea, P rats who were administered clonidine (a noradrenergic signaling inhibitor) reduced alcohol consumption and saccharin consumption, but not water consumption [111]. In another example, P rats who were administered TP-10 (a dual-specificity cyclic adenosine monophosphate/cyclic guanosine monophosphate-inhibiting enzyme inhibitor) reduced their alcohol and saccharin self administration [112]. This illustrates the utility of using the endophenotype concept in a translational manner to develop potential therapeutic targets for AUD.
