Strain differences in urocortin expression in the Edinger - Westphal nucleus and its relation to alcohol-induced hypothermia

R. K. Bachtell, N. O. Tsivkovskaia, A. E. Ryabinin

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

The Edinger - Westphal nucleus is the primary source of urocortin in rodent brain. Mapping of inducible transcription factors has shown that the Edinger - Westphal nucleus is preferentially sensitive to ethanol self-administration. In the present study we have immunohistochemically compared expression of urocortin and c-Fos in naive and ethanol-treated C57BL/6J and DBA/2J mouse inbred strains. We found that C57BL/6J mice possess significantly higher numbers of urocortin-expressing cells in the Edinger - Westphal compared to DBA/2J mice. Subsequent histological analysis confirmed a lower number of large neurons in the DBA/2J Edinger - Westphal nucleus. Surprisingly, despite the differences in structure, no strain differences were observed in the number of c-Fos-containing cells after acute (0.6-4.8 g/kg, i.p.) and repeated (2.4 g/kg, 14 days, one injection/day) administration of ethanol. Double-label immunohistochemistry showed that ethanol-induced c-Fos expression is present in different sets of Edinger - Westphal cells between the strains. Specifically, expression of c-Fos in C57BL/6J mice is preferentially induced in urocortin cells, while c-Fos in DBA/2J mice occurs in a mixed population of cells. Behavioral analysis of the B6D2 F2 intercross, a heterogeneous mouse strain, showed that the number of urocortin cells is positively correlated with basal temperatures and ethanol-induced hypothermia. Involvement of the Edinger - Westphal in alcohol-induced hypothermia is further confirmed by analysis of urocortin cells in the HOT/COLD selected lines. These results provide evidence that C57BL/6J and DBA/2J mice have structural differences in the Edinger - Westphal that can result in activation of different populations of neurons upon alcohol intoxication contributing to differential thermoregulation between these inbred strains.

Original languageEnglish (US)
Pages (from-to)421-434
Number of pages14
JournalNeuroscience
Volume113
Issue number2
DOIs
StatePublished - Aug 12 2002

Keywords

  • C57BL/6
  • DBA/2
  • HOT/COLD
  • Inbred strains
  • Selected lines
  • c-Fos

ASJC Scopus subject areas

  • Neuroscience(all)

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