Differences in Ethanol Drinking and Nucleus Accumbens Opioid Expression in Male and Female Obesity-Prone and Obesity-Resistant Rats.

Literature suggests that there may be overlap between proneness to overeating-induced obesity and excessive alcohol drinking, and that this may occur in part via the endogenous opioid system in the nucleus accumbens (NAc). To investigate this, we used rats selectively bred for their susceptibility or resistance to diet-induced obesity (obesity-prone, OP, and obesity-resistant, OR), and examined their (1) ethanol drinking under the intermittent access two-bottle-choice procedure, (2) sucrose drinking under the intermittent access two-bottle-choice procedure, and (3) enkephalin, dynorphin, and opioid receptor mRNA in the NAc core and NAc shell. While we found no major differences in measures of sucrose drinking, male OP compared to OR rats had higher levels of 24-hour ethanol drinking and preference, while female OP compared to OR rats had higher levels of binge-like (30-minute) ethanol drinking and corresponding blood ethanol concentrations. In parallel, both male and female OP compared to OR rats had higher expression of enkephalin but not dynorphin mRNA in the NAc core, and males had higher expression of mRNAs encoding mu, delta, and kappa opioid receptors in the NAc core. Together, these results show that proneness to obesity is associated with excessive ethanol drinking prior to the onset of obesity. Further, they suggest that this could be driven in part through differences in the NAc endogenous opioid system, particularly for males and via the NAc core. This supports the idea that proneness to excessive alcohol drinking may share neurobehavioral mechanisms with susceptibility to diet-induced obesity.