Differences in the urocortin 1 system between long-sleep and short-sleep mice

There is evidence that the peptide urocortin 1 (Ucn1) may be involved in mediating some of the effects of ethanol. The purpose of the present study was to characterize Ucn1 immunoreactivity in mice selectively bred for either high or low sensitivity to ethanol-induced sedation, with additional differences in their response to ethanol-induced hypothermia. The brains of naïve male mice of the inbred long sleep/short sleep (ILS/ISS) selected lines were analyzed by immunohistochemistry. Significant differences were found between lines in the number of Ucn1-containing cells in the non-preganglionic Edinger-Westphal nucleus (npEW, the main source of Ucn1 in the brain); with the ISS mice having more cells. However, significant differences in the optical density of Ucn1 immunoreactivity in individual npEW cells and differences in cell area were also found between lines, with ILS mice having a greater density of Ucn1 per cell and having larger cells in the npEW. Importantly, the ILS mice also had a significantly greater number of Ucn1-positive terminal fibers than ISS mice in the lateral septum and the dorsal raphe nucleus, projection areas of Ucn1-containing neurons. These results suggest that the greater sensitivity of ILS than ISS mice to the hypothermic effects of ethanol could be mediated by stronger innervation of the dorsal raphe by Ucn1-containing fibers. In addition, these results lend further support to previous findings implicating Ucn1-containing projections from npEW to the dorsal raphe in ethanol-induced hypothermia.