Urocortin 1 expression in five pairs of rat lines selectively bred for differences in alcohol drinking

Rationale There is accumulating evidence that the neuropeptide urocortin 1 (Ucn1) is involved in alcohol consumption. Thus far, however, most studies have been performed in mice. Objectives The purpose of the present study was to characterize Ucn1 expression in rats selectively bred for either high or low alcohol intake. Methods Brains from naive male rats of five pairs of independently selected lines (iP/iNP, AA/ANA, HARF/LARF, HAD1/LAD1, and HAD2/LAD2) were analyzed by immunohistochemistry. Results Significant differences were found between iP/iNP, HARF/LARF, and HAD2/LAD2 in number of Ucn1-containing cells in the Edinger–Westphal (EW) nucleus (the main source of Ucn1 in the brain), whereas no significant differences were found between HAD1/LAD1 and AA/ANA. Similarly, significant differences in the optical density of Ucn1 immunoreactivity in EW were found between iP/iNP, HARF/LARF, and HAD2/LAD2, whereas no differences on this measure were found between HAD1/LAD1 and AA/ANA. In the lateral septum (LS, the main projection area of Ucn1-containing neurons in the rat), significant differences were found only between AA/ANA and HAD2/LAD2; however, a meta-analysis indicated that across all five lines, preferring animals had a significantly greater number of Ucn1-positive fibers than nonpreferring animals. Conclusions These results provide evidence that, in rats, Ucn1 may be involved in regulation of alcohol intake, and that this regulation may occur through the Ucn1 projections to LS.