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

• Published in: Neuroscience 2002-01, Vol.113 (2), p.421-434
• Main Authors: Bachtell, R.K, Tsivkovskaia, N.O, Ryabinin, A.E
• Format: Article
• Language: English
• Subjects: Alcoholism and acute alcohol poisoning; Animals; Behavior, Animal - physiology; Biological and medical sciences; Brain - drug effects; Brain - metabolism; c-Fos; C57BL/6; Corticotropin-Releasing Hormone - metabolism; DBA/2; Dose-Response Relationship, Drug; Drug Administration Schedule; Ethanol - administration & dosage; Ethanol - metabolism; Ethanol - pharmacology; Female; HOT/COLD; Hypothermia - chemically induced; Hypothermia - genetics; Hypothermia - metabolism; Hypothermia - pathology; Immunohistochemistry; inbred strains; Male; Medical sciences; Mice; Mice, Inbred C57BL - genetics; Mice, Inbred DBA - genetics; Neurons - metabolism; Proto-Oncogene Proteins c-fos - metabolism; selected lines; Sex Characteristics; Species Specificity; Tissue Distribution; Toxicology; Urocortins
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(02)00174-4

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.