The urocortin (Ucn) neurons of the midbrain-localized Edinger-Westphal nucleus (EW) are robustly responsive to ethanol (EtOH) administration, and send projections to the dorsal raphe nucleus (DRN). The DRN contains corticotropin-releasing factor type 2 receptors (CRFR2) that are responsive to Ucn, a peptide synthesized in the EW. ? ? In addition, the DRN has been shown to be involved in regulation of body temperature, a function greatly affected by EtOH administration. The goal of the proposed studies is to identify the role that the urocortinergic projections from the alcohol-responsive EWto the DRN have in EtOH-induced hypothermia.
The specific aims of the proposed studies are: 1) To determine what the differences are in the extent of Ucn-positive EW-to-DRN projections and CRF receptor binding in DRN between two pairs of selectively bred lines of mice, both of which show significant differences in sensitivity to EtOH-induced hypothermia. 2) To determine whether EtOH-induced hypothermia is dependent on Ucn and the EW by examining the thermoregulatory response to EtOH in Ucn knockout mice. 3) To pharmacologically assess the role of the Ucn-containing projections from EW-DRN in hypothermia, and to determine whether CRFR2 receptors and/or 5HT1A receptors on serotonergic neurons in the DRN are mediating the hypothermia. ? ? ?
| Steiner, Alexandre A; Turek, Victoria F; Almeida, Maria C et al. (2007) Nonthermal activation of transient receptor potential vanilloid-1 channels in abdominal viscera tonically inhibits autonomic cold-defense effectors. J Neurosci 27:7459-68 |
