Differential expression of NPY and its receptors in alcohol-preferring AA and alcohol-avoiding ANA rats

Background: Central neuropeptide Y (NPY) is known to control feeding and st ress responses. Recently, it has been suggested that NPY also has a role in regulation of alcohol consumption. Methods: NPY and NPY receptor expression in genetically selected alcohol-pr eferring (AA), alcohol-nonpreferring (ANA), and Wistar rats were investigat ed. Expression was assessed using in situ hybridization histochemistry with riboprobes specific for preproNPY, Y1, and Y2 receptors. Effects of centra l NPY administration on ethanol self-administration were also examined in A A, ANA, and Wistar rats by using oral operant self-administration. Results: NPY mRNA expression was higher in ANA than in both AA and Wistar r ats in the hippocampal CA region and dentate gyrus, whereas AA and Wistar d id not differ from each other. No differences in NPY expression were found in the other regions analyzed: cingulate cortex, medial nucleus of the amyg dala, arcuate, and paraventricular nuclei of the hypothalamus. YI receptor mRNA expression did not differ between the three lines. Y2 expression was h igher in the dentate gyrus of both AA and ANA rats than in Wistar subjects. In the medial amygdala, Y2 mRNA was reduced in the AA line, compared to bo th ANA and Wistar rats. NPY injected intracerebroventricularly (1.5-3.0 nmo l) did not affect operant ethanol self-administration in any of the three l ines examined. Conclusion: The NPY system seems to differ in several respects between rat lines with different levels of alcohol preference. Differences observed wit hin the hippocampus could be related to behavioral traits other than alcoho l intake but it is also possible that elevated hippocampal expression of NP Y in the ANA rats contributes to the low alcohol intake of this line. Aberr ant NPY expression and/function within the amygdala complex could contribut e to alcohol preference and constitute an anatomic substrate of the effects of NPY expression on alcohol intake observed previously in genetically mod ified animals.