Front Psychiatry. 2013 Apr 12;4:23. doi: 10.3389/fpsyt.2013.00023. eCollection 2013.

Role of a genetic polymorphism in the corticotropin-releasing factor receptor 1 gene in alcohol drinking and seeking behaviors of marchigian sardinian alcohol-preferring rats.

Frontiers in psychiatry

Lydia O Ayanwuyi, Francisca Carvajal, Jose M Lerma-Cabrera, Esi Domi, Karl Björk, Massimo Ubaldi, Markus Heilig, Marisa Roberto, Roberto Ciccocioppo, Andrea Cippitelli

PMID: 23630503 PMCID: PMC3624086 DOI: 10.3389/fpsyt.2013.00023

Abstract

Marchigian Sardinian alcohol-preferring (msP) rats exhibit innate preference for alcohol, are highly sensitive to stress and stress-induced alcohol seeking. Genetic analysis showed that over-expression of the corticotropin-releasing factor (CRF) system of msP rats is correlated with the presence of two single nucleotide polymorphisms (SNPs) occurring in the promoter region (position -1836 and -2097) of the CRF1 receptor (CRF1-R) gene. Here we examined whether these point mutations were associated to the innate alcohol preference, stress-induced drinking, and seeking. We have recently re-derived the msP rats to obtain two distinct lines carrying the wild type (GG) and the point mutations (AA), respectively. The phenotypic characteristics of these two lines were compared with those of unselected Wistar rats. Both AA and GG rats showed similar patterns of voluntary alcohol intake and preference. Similarly, the pharmacological stressor yohimbine (0.0, 0.625, 1.25, and 2.5 mg/kg) elicited increased operant alcohol self-administration under fixed and progressive ratio reinforcement schedules in all three lines. Following extinction, yohimbine (0.0, 0.625, 1.25, and 2.5 mg/kg) significantly reinstated alcohol seeking in the three groups. However, at the highest dose this effect was no longer evident in AA rats. Treatment with the CRF1-R antagonist antalarmin (0, 5, 10, and 20 mg/kg) significantly reduced alcohol-reinforced lever pressing in the AA line (10 and 20 mg/kg) while a weaker or no effect was observed in the Wistar and the GG group, respectively. Finally, antalarmin significantly reduced yohimbine-induced increase in alcohol drinking in all three groups. In conclusion, these specific SNPs in the CRF1-R gene do not seem to play a primary role in the expression of the msP excessive drinking phenotype or stress-induced drinking but may be associated with a decreased threshold for stress-induced alcohol seeking and an increased sensitivity to the effects of pharmacological blockade of CRF1-R on alcohol drinking.

Keywords: CRF; SNP; msP; relapse; self-administration; yohimbine

References

1. J Neurosci. 1995 Aug;15(8):5439-47 - PubMed
2. Neuroscience. 1988 Dec;27(3):897-904 - PubMed
3. Psychopharmacologia. 1961;2:93-106 - PubMed
4. Mol Psychiatry. 2011 Aug;16(8):809-17 - PubMed
5. Pharmacol Biochem Behav. 2002 May;72(1-2):213-20 - PubMed
6. Trends Neurosci. 2007 Aug;30(8):399-406 - PubMed
7. Psychopharmacology (Berl). 2010 Sep;211(4):367-75 - PubMed
8. Neuropsychopharmacology. 2010 May;35(6):1241-52 - PubMed
9. Psychopharmacology (Berl). 2005 May;179(2):366-73 - PubMed
10. Res Publ Assoc Res Nerv Ment Dis. 1992;70:231-52 - PubMed
11. Alcohol. 2009 Nov;43(7):491-8 - PubMed
12. Endocrinology. 1996 Dec;137(12):5747-50 - PubMed
13. Science. 1982 Mar 12;215(4538):1394-6 - PubMed
14. Pharmacol Biochem Behav. 2012 Sep;102(3):400-6 - PubMed
15. Psychopharmacology (Berl). 2005 Apr;178(4):367-80 - PubMed
16. Mol Psychiatry. 2006 Jun;11(6):594-602 - PubMed
17. Psychopharmacology (Berl). 2007 Dec;195(3):345-55 - PubMed
18. Drug Alcohol Depend. 2013 Mar 1;128(3):175-86 - PubMed
19. Psychopharmacology (Berl). 2003 Jul;168(1-2):3-20 - PubMed
20. Neuropsychopharmacology. 2005 Sep;30(9):1662-9 - PubMed
21. Psychoneuroendocrinology. 2010 Jul;35(6):887-95 - PubMed
22. Pharmacol Rep. 2012;64(2):449-53 - PubMed
23. Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15236-41 - PubMed
24. Psychopharmacology (Berl). 2010 Feb;208(3):417-26 - PubMed
25. Nat Rev Neurosci. 2011 Oct 20;12(11):670-84 - PubMed
26. Arch Gen Psychiatry. 1981 Aug;38(8):861-8 - PubMed
27. J Neurosci. 2007 Mar 7;27(10):2718-26 - PubMed
28. Pharmacol Biochem Behav. 2012 Jan;100(3):522-9 - PubMed
29. Neuroscience. 2006;138(1):235-43 - PubMed
30. PLoS One. 2008;3(10):e3620 - PubMed
31. FASEB J. 2002 Jan;16(1):27-35 - PubMed
32. Alcohol Clin Exp Res. 1985 Dec;9(6):475-92 - PubMed
33. Psychopharmacology (Berl). 2010 Oct;212(3):431-9 - PubMed
34. J Pharmacol Exp Ther. 2007 Dec;323(3):846-54 - PubMed
35. J Neurosci. 2006 Nov 1;26(44):11324-32 - PubMed
36. Eur J Neurosci. 2007 Jul;26(2):476-86 - PubMed
37. Neuropharmacology. 2007 Dec;53(8):958-66 - PubMed
38. Psychopharmacology (Berl). 2006 Dec;189(2):175-86 - PubMed
39. Alcohol Clin Exp Res. 2004 Nov;28(11):1676-82 - PubMed
40. Psychopharmacology (Berl). 2001 Dec;158(4):374-81 - PubMed
41. Biol Psychiatry. 2010 May 1;67(9):831-9 - PubMed
42. FASEB J. 2008 Jul;22(7):2113; author reply 2113-4 - PubMed
43. Neuropsychopharmacology. 2003 Aug;28(8):1546-52 - PubMed
44. Neuropsychopharmacology. 2011 May;36(6):1178-86 - PubMed
45. Pharmacol Biochem Behav. 2007 Apr;86(4):813-21 - PubMed
46. Nat Neurosci. 2005 Nov;8(11):1471-80 - PubMed
47. Physiol Behav. 1995 Jun;57(6):1181-5 - PubMed
48. Psychopharmacology (Berl). 2001 Dec;158(4):343-59 - PubMed
49. J Neurosci. 1997 Apr 1;17(7):2605-14 - PubMed
50. Pharmacol Ther. 2011 Feb;129(2):149-71 - PubMed
51. Psychopharmacology (Berl). 2008 Jul;198(4):449-60 - PubMed
52. Pharmacol Rev. 2001 Jun;53(2):209-43 - PubMed
53. Alcohol Clin Exp Res. 2008 Feb;32(2):259-65 - PubMed
54. J Neurosci. 1998 Jul 15;18(14):5529-36 - PubMed
55. Neuropsychopharmacology. 2006 Oct;31(10):2188-96 - PubMed
56. Addict Biol. 2007 Mar;12(1):30-4 - PubMed
57. Alcohol Clin Exp Res. 2008 Sep;32(9):1535-42 - PubMed
58. Am J Addict. 2012 Jul-Aug;21(4):343-7 - PubMed
59. Curr Top Behav Neurosci. 2013;13:251-69 - PubMed
60. Biol Psychiatry. 2007 Jan 1;61(1):78-86 - PubMed
61. Alcohol Clin Exp Res. 2011 Jan;35(1):166-74 - PubMed
62. Psychopharmacology (Berl). 1999 May;144(2):151-7 - PubMed
63. Alcohol Clin Exp Res. 1991 Jun;15(3):438-59 - PubMed
64. Psychiatr Clin North Am. 1999 Jun;22(2):289-99, viii - PubMed
65. Alcohol Alcohol Suppl. 1991;1:121-4 - PubMed
66. Pharmacol Biochem Behav. 1997 Jul;57(3):441-7 - PubMed
67. Biol Psychiatry. 2008 Jan 15;63(2):139-45 - PubMed
68. Addict Biol. 2006 Sep;11(3-4):339-55 - PubMed
69. Synapse. 1996 May;23(1):39-51 - PubMed
70. Biol Psychiatry. 2011 Apr 1;69(7):642-9 - PubMed
71. Synapse. 1996 May;23(1):28-38 - PubMed
72. Pharmacol Ther. 2005 Oct;108(1):86-93 - PubMed
73. Brain Res. 2010 Feb 16;1314:3-14 - PubMed
74. Endocrinology. 1992 Sep;131(3):1369-76 - PubMed

Publication Types

• Journal Article

Grant support

• R01 AA014351/AA/NIAAA NIH HHS/United States
• R01 AA017447/AA/NIAAA NIH HHS/United States