Skip to main content
SpringerLink
Log in

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

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Bachtell RK, Wang Y-M, Freeman P, Risinger FO, Ryabinin AE (1999) Alcohol drinking produces brain region-selective changes in expression of inducible transcription factors. Brain Res 847:157–165

    Article  PubMed  CAS  Google Scholar 

  • Bachtell RK, Tsivkovskaia NO, Ryabinin AE (2002) Strain differences in urocortin expression in the Edinger–Westphal nucleus and its relation to alcohol-induced hypothermia. Neurosci 113:421–434

    Article  CAS  Google Scholar 

  • Bachtell RK, Weitemier AZ, Galvan-Rosas A, Tsivkovskaia NO, Risinger FO, Phillips TJ, Grahame NJ, Ryabinin AE (2003) The Edinger–Westphal-lateral septum urocortin pathway and its relationship to alcohol consumption. J Neurosci 15:2477–2487

    Google Scholar 

  • Bachtell RK, Weitemier AZ, Ryabinin AE (2004) Lesions of the Edinger–Westphal nucleus in C57BL/6J mice disrupt ethanol-induced hypothermia and ethanol consumption. Eur J Neurosci 20:1613–1623

    Article  PubMed  Google Scholar 

  • Bale TL, Vale WW (2004) CRF and CRF receptors: role in stress responsivity and other behaviors. Annu Rev Pharmacol Toxicol 44:525–557

    Article  PubMed  CAS  Google Scholar 

  • Becker BJ (1994) Combining significance levels. In: Cooper H, Hedges LV (eds) The handbook of research synthesis. Russell Sage, New York, pp 215–230

    Google Scholar 

  • Bittencourt JC, Vaughan J, Arias C, Rissman RA, Vale WW, Sawchenko PE (1999) Urocortin expression in rat brain: evidence against a pervasive relationship of urocortin-containing projections with targets bearing type 2 CRF receptors. J Comp Neurol 415:285–312

    Article  PubMed  CAS  Google Scholar 

  • Cavani JA, Reiner A, Cuthbertson SL, Bittencourt JC, Toledo CA (2003) Evidence that urocortin is absent from neurons of the Edinger–Westphal nucleus in pigeons. Braz J Med Biol Res 36:1695–1700

    Article  PubMed  CAS  Google Scholar 

  • Chang SL, Patel NA, Romero AA (1995) Activation and desensitization of Fos immunoreactivity in the rat brain following ethanol administration. Brain Res 679:89–98

    Article  PubMed  CAS  Google Scholar 

  • Crabbe JC, Phillips TJ, Kosobud A, Belknap JK (1990) Estimation of genetic correlation: interpretation of experiments using selectively bred and inbred animals. Alcohol Clin Exp Res 14:141–151

    Article  PubMed  CAS  Google Scholar 

  • Czachowski CL, Samson HH (2002) Ethanol- and sucrose-reinforced appetitive and consummatory responding in HAD1, HAD2, and P rats. Alcohol Clin Exp Res 26:1653–1661

    PubMed  CAS  Google Scholar 

  • Ehlers CL, Chaplin RI, Wall TL, Lumeng L, Li TK, Owens MJ, Nemeroff CB (1992) Corticotropin releasing factor (CRF): studies in alcohol preferring and non-preferring rats. Psychopharmacol 106:359–364

    Article  CAS  Google Scholar 

  • Iovino M, Steardo L (1985) Thirst and vasopressin secretion following central administration of angiotensin II in rats with lesions of the septal area and subfornical organ. Neuroscience 15:61–67

    Article  PubMed  CAS  Google Scholar 

  • Klooster J, Beckers HJM, Vrensen GFJM, VanderWant JJL (1993) The peripheral and central projections of the Edinger–Westphal nucleus in the rat. A light and electron microscopic tracing study. Brain Res 632:260–273

    Article  PubMed  CAS  Google Scholar 

  • Kozicz T, Yanaihara H, Arimura A (1998) Distribution of urocortin-like immunoreactivity in the central nervous system of the rat. J Comp Neurol 391:1–10

    Article  PubMed  CAS  Google Scholar 

  • Lê AD, Israel Y, Juzytsch W, Quan B, Harding S (2001) Genetic selection for high and low alcohol consumption in a limited-access paradigm. Alcohol Clin Exp Res 25:1613–1620

    Article  PubMed  Google Scholar 

  • Lodge DJ, Lawrence AJ (2003) The CRF1 receptor antagonist antalarmin reduces volitional ethanol consumption in isolation-reared fawn-hooded rats. Neuroscience 117:243–247

    Article  PubMed  CAS  Google Scholar 

  • McBride WJ, Li TK (1998) Animal models of alcoholism: neurobiology of high alcohol-drinking behavior in rodents. Crit Rev Neurobiol 12:339–369

    PubMed  CAS  Google Scholar 

  • Milner PM (1991) Brain-stimulation reward: a review. Can J Psychol 45:1–36

    PubMed  CAS  Google Scholar 

  • Murphy JM, Stewart RB, Bell RL, Badia-Elder NE, Carr LG, McBride WJ, Lumeng L, Li TK (2002) Phenotypic and genotypic characterization of the Indiana University rat lines selectively bred for high and low alcohol preference. Behav Genet 32:363–388

    Article  PubMed  Google Scholar 

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic, London

    Google Scholar 

  • Ryabinin AE, Criado JR, Henricksen SJ, Bloom FE, Wilson MC (1997) Differential sensitivity of c-Fos expression in hippocampus and other brain regions to moderate and low doses of alcohol. Mol Psychiatry 2:32–43

    Article  PubMed  CAS  Google Scholar 

  • Ryabinin AE, Bachtell RK, Heinrichs SC, Lee S, Rivier C, Olive MF, Mehmert KK, Camarini R, Kim JA, Koenig HN, Nannini MA, Hodge CW, Roberts AJ, Koob GF (2002) The corticotropin-releasing factor/urocortin system and alcohol. Alcohol Clin Exp Res 26:714–722

    Article  PubMed  CAS  Google Scholar 

  • Ryabinin AE, Galvan-Rosas A, Bachtell RK, Risinger FO (2003) High alcohol/sucrose consumption during dark circadian phase in C57BL/6J mice: involvement of hippocampus, lateral septum and urocortin-positive cells of the Edinger–Westphal nucleus. Psychopharmacol 165:296–305

    CAS  Google Scholar 

  • Sheehan TP, Chambers RA, Russell DS (2004) Regulation of affect by the lateral septum: implications for neuropsychiatry. Brain Res Rev 46:71–117

    Article  PubMed  Google Scholar 

  • Sokal RR, Rohlf FJ (1995) Biometry. Freeman, San Francisco, pp 794–797

    Google Scholar 

  • Szczepanska-Sadowska E, Sadowski B, Sobocinska J (1981) Enhancement of osmotic thirst elicited by electric stimulation of the limbic system in dogs. J Physiol 77:671–674

    CAS  Google Scholar 

  • Taghzouti K, Simon H, Tazi A, Dantzer R, Le Moal M (1985) The effect of 6-OHDA lesions of the lateral septum on schedule-induced polydipsia. Behav Brain Res 15:1–8

    Article  PubMed  CAS  Google Scholar 

  • Topple AN, Hunt GE, McGregor IS (1998) Possible neural substrates of beer-craving in rats. Neurosci Lett 252:99–102

    Article  PubMed  CAS  Google Scholar 

  • Valdez GR, Roberts AJ, Chan K, Davis H, Brennan M, Zorrilla EP, Koob GF (2002) Increased ethanol self-administration and anxiety-like behavior during acute ethanol withdrawal and protracted abstinence: regulation by corticotropin-releasing factor. Alcohol Clin Exp Res 26:1494–1501

    PubMed  CAS  Google Scholar 

  • Vasconcelos LA, Donaldson C, Sita LV, Casatti CA, Lotfi CF, Wang L, Cadinouche MZ, Frigo L, Elias CF, Lovejoy DA, Bittencourt JC (2003) Urocortin in the central nervous system of a primate (Cebus apella): sequencing, Immunohistochemical, and hybridization histochemical characterization. J Comp Neurol 463:157–175

    Article  PubMed  CAS  Google Scholar 

  • Vasudev R, Gentil CG, Covian MR (1985) Taste preferences in a free-choice situation following electrical stimulation and lesion of septal area in rats. Physiol Behav 34:619–624

    Article  PubMed  CAS  Google Scholar 

  • Vaughan J, Donaldson C, Bittencourt J, Perrin MH, Lewis K, Sutton S, Chan R, Turnbull AV, Lovejoy D, Rivier C, Rivier J, Sawchenko PE, Vale W (1995) Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor. Nature 378:287–292

    Article  PubMed  CAS  Google Scholar 

  • Warwick RB (1954) The ocular parasympathetic nerve supply and its mesencephalic sources. J Anat 88:71–93

    PubMed  CAS  Google Scholar 

  • Weitemier AZ, Ryabinin AE (2004) Repeated alcohol exposure regulates urocortin I innervation of the lateral septum and dorsal raphe in mice. Alcohol Clin Exp Res 28:5(Suppl):56A

    Google Scholar 

  • Weitemier AZ, Woerner A, Backstrom P, Hyytia P, Ryabinin AE (2001) Expression of c-Fos in Alko alcohol rats responding for ethanol in an operant paradigm. Alcohol Clin Exp Res 25:704–710

    Article  PubMed  CAS  Google Scholar 

  • Weninger SC, Dunn AJ, Muglia LJ, Dikkes P, Miczek KA, Swiergiel AH, Berridge CW, Majzoub JA (1999) Stress-induced behaviors require the corticotropin-releasing hormone (CRH) receptor, but not CRH. Proc Natl Acad Sci U S A 96:8283–8288

    Article  PubMed  CAS  Google Scholar 

  • Wolf FM (1986) Meta-analysis: quantitative methods for research synthesis. Sage University Press, Hollywood, CA, pp 18–19

    Google Scholar 

Download references

Acknowledgements

The authors would like to thank Adam Weitemier for valuable technical assistance with the study and Dr. John Belknap for help with the statistical analyses.

This work was supported by NIH grants AA10760, AA13738 (A.E.R.), and AA13108 (A.D.L.).

Author information

Authors and Affiliations

  1. Portland Alcohol Research Center, Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, 97239, USA

    V. F. Turek, N. O. Tsivkovskaia & A. E. Ryabinin

  2. Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland

    P. Hyytia

  3. Department of Pharmacology and Psychiatry, University of Toronto, Ontario, Canada

    S. Harding & A. D. Lê

Authors
  1. V. F. Turek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. O. Tsivkovskaia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Hyytia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Harding
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. D. Lê
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. E. Ryabinin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. F. Turek.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Turek, V.F., Tsivkovskaia, N.O., Hyytia, P. et al. Urocortin 1 expression in five pairs of rat lines selectively bred for differences in alcohol drinking. Psychopharmacology 181, 511–517 (2005). https://doi.org/10.1007/s00213-005-0011-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-005-0011-x

Keywords

Search

Navigation