DIFFERENCES BETWEEN ALCOHOL-PREFERRING (AA) AND ALCOHOL-AVOIDING (ANA) RATS IN THE PRODYNORPHIN AND PROENKEPHALIN SYSTEMS

The motivation to drink alcohol and the eventual risk of becoming addicted are in part genetically determined. Because opioid peptides are considered central to motivated behaviors, we have analyzed opioid peptides in relevant areas of the brain of two outbred lines of rats: the alcohol-preferring [Alko Alcohol (AA)] line who voluntarily drink alcohol and the alcohol-avoiding [Alko Non-Alcohol (ANA)] line with negligible intake. (Met)enkephalinArg(6)Phe(7) (MEAP) was measured as a marker of proenkephalin, and dynorphin A, dynorphin B, and (Leu)enkephalinArg(6) as markers of the prodynorphin system. The major line differences and effects of alcohol intake were observed in mesolimbic brain areas. The mesolimbic dopamine pathway, which projects from the ventral tegmental area (VTA) to the nucleus accumbens, is central in the reward system. Basal levels of MEAP and dynorphin peptides were low in the nucleus accumbens of AA rats, whereas (Leu)enkephalinArg(6) levels were lower in the VTA of these rats. Alcohol drinking caused MEAP levels in the accumbens to rise, but had no effect on prodynorphin peptides. Opioids also influence the nigrostriatal dopamine pathway. However, this study showed no significant differences for any peptide between rat lines, or effect of alcohol intake, in either substantia nigra or striatum, except for a decrease of nigral and striatal (Leu)enkephalinArg(6) levels in alcohol drinking AA rats. Large line differences were observed in the pituitary gland. AA rats had high basal levels of MEAP, which became even higher after voluntary alcohol consumption for 4 weeks, and low levels of dynorphin peptides, not affected by alcohol drinking. In summary, there are differences in baseline and drinking-induced opioid peptide levels between the rat lines. First, the AA rats have lower dynorphin levels in the nucleus accumbens, which may increase the sensitivity to the reinforcing effects of dopamine. Second, the AA rats who have lower MEAP levels in the nucleus accumbens, respond by an increase on alcohol intake, which may strengthen the motivation to continue alcohol drinking. Thus, there is a possible relationship between differences in opioid peptide levels and differences in the motivation to drink alcohol between these two lines of rats.