Pre-clinical evidence that Corticotropin-Releasing Factor (CRF) receptor antagonists are promising targets for pharmacological treatment of alcoholism

CNS and Neurological Disorders - Drug Targets

Volumn 9, Issue 1, 2010, Pages 77-86

  Lowery, Emily G ^a   Thiele, Todd E ^a,b  

^a UNIVERSITY OF NORTH CAROLINA   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

Alcoholism; Corticotropin receptor; Corticotropin releasing factor; Dependence; Ethanol; Relapse; Urocortin; Withdrawal

Indexed keywords

3 (4 CHLORO 2 ORPHOLIN 4 YL THIAZOL 5 YL) 8 (1 ETHYLPROPYL) 2,6 DIMETHYL IMIDAZO[1,2 B]PYRIDAZINE; 3 (6 DIMETHYLAMINO 4 METHYL 3 PYRIDINYL) 7 DIPROPYLAMINO 2,5 DIMETHYLPYRAZOLO[1,5 A]PYRIMIDINE; 4 [4 (3 FLUOROPHENYL) 1,2,3,6 TETRAHYDRO 1 PYRIDINYL] 2 [N ETHYL N (4 ISOPROPYL 2 METHYLTHIOPHENYL)AMINO] 6 METHYLPYRIMIDINE; ALPHA HELICAL CORTICOTROPIN RELEASING FACTOR; ANTALARMIN; CORTICOTROPIN RELEASING FACTOR; CORTICOTROPIN RELEASING FACTOR ANTAGONIST; CORTICOTROPIN RELEASING FACTOR RECEPTOR 1; CP 154,526; D PHENYLALANINE CORTICOTROPIN RELEASING FACTOR; LWH 63; MJL 1 109 2; MPZP; UNCLASSIFIED DRUG; UROCORTIN I; UROCORTIN III;

ALCOHOL ABUSE; ALCOHOL CONSUMPTION; ALCOHOLISM; ANIMAL EXPERIMENT; DISSOCIATION CONSTANT; EMOTION; MOUSE; NONHUMAN; REVIEW;

EID: 77949902559     PISSN: 18715273     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152710790966605     Document Type: Review

References (109)

1. Hauger, R.L.; Risbrough, V.; Brauns, O.; Dautzenberg, F.M. Corticotropin releasing factor (CRF) receptor signaling in the central nervous system: new molecular targets. CNS Neurol. Disord. Drug Targets, 2006, 5, 453-479.
2. Van Pett, K.; Viau, V.; Bittencourt, J.C.; Chan, R.K.; Li, H.Y.; Arias, C.; Prins, G.S.; Perrin, M.; Vale, W.; Sawchenko, P.E. Distribution of mRNAs encoding CRF receptors in brain and pituitary of rat and mouse. J. Comp. Neurol., 2000, 428, 191-212.
3. Heilig, M.; Koob, G.F. A key role for corticotropin-releasing factor in alcohol dependence. Trends Neurosci., 2007, 30, 399-406.
4. Gulyas, J.; Rivier, C.; Perrin, M.; Koerber, S.C.; Sutton, S.; Corrigan, A.; Lahrichi, S.L.; Craig, A.G.; Vale, W.; Rivier, J. Potent, structurally constrained agonists and competitive antagonists of corticotropin-releasing factor. Proc. Natl. Acad. Sci. USA, 1995, 92, 10575-10579.
5. Pioszak, A.A.; Parker, N.R.; Suino-Powell, K.; Xu, H.E. Molecular recognition of corticotropin-releasing factor by its G-protein-coupled receptor CRFR1. J. Biol. Chem., 2008, 283, 32900-32912.
6. Ryabinin, A.E.; Bachtell, R.K.; Heinrichs, S.C.; Lee, S.; Rivier, C.; Olive, M.F.; Mehmert, K.K.; Camarini, R.; Kim, J.A.; Koenig, H.N.; Nannini, M.A.; Hodge, C.W.; Roberts, A.J.; Koob, G.F. The corticotropin-releasing factor/urocortin system and alcohol. Alcohol. Clin. Exp. Res., 2002, 26, 714-722.
7. Venihaki, M.; Sakihara, S.; Subramanian, S.; Dikkes, P.; Weninger, S.C.; Liapakis, G.; Graf, T.; Majzoub, J.A. Urocortin III, a brain neuropeptide of the corticotropin-releasing hormone family: modulation by stress and attenuation of some anxiety-like behaviours. J. Neuroendocrinol., 2004, 16, 411-422.
8. Fu, Y.; Neugebauer, V. Differential mechanisms of CRF1 and CRF2 receptor functions in the amygdala in pain-related synaptic facilitation and behavior. J. Neurosci., 2008, 28, 3861-3876.
9. Zhao, Y.; Valdez, G.R.; Fekete, E.M.; Rivier, J.E.; Vale, W.W.; Rice, K.C.; Weiss, F.; Zorrilla, E.P. Subtype-selective corticotropin-releasing factor receptor agonists exert contrasting, but not opposite, effects on anxiety-related behavior in rats. J. Pharmacol. Exp. Ther., 2007, 323, 846-854.
10. Kozicz, T. CRF and CRF-related peptides in stress adaptation: from invertebrates to man. Gen. Comp. Endocrinol., 2007, 153, 198-199.
11. Kozicz, T. On the role of urocortin 1 in the non-preganglionic Edinger-Westphal nucleus in stress adaptation. Gen. Comp. Endocrinol., 2007, 153, 235-240.
12. Koob, G.F. Alcoholism: allostasis and beyond. Alcohol. Clin. Exp. Res., 2003, 27, 232-243.
13. Clark, M.S.; Kaiyala, K.J. Role of corticotropin-releasing factor family peptides and receptors in stress-related psychiatric disorders. Semin. Clin. Neuropsychiatry, 2003, 8, 119-136.
14. Latchman, D.S. Urocortin. Intl. J. Biochem. Cell Biol., 2002, 34, 907-910.
15. Breese, G.R.; Chu, K.; Dayas, C.V.; Funk, D.; Knapp, D.J.; Koob, G.F.; Le, A.D.; O'Dell, L.; Overstreet, D.H.; Roberts, A.J.; Sinha, R.; Valdez, G.R.; Weiss, F. Stress enhancement of craving during sobriety: a risk for relapse. Alcohol. Clin. Exp. Res., 2005, 29, 185-195.
16. Koob, G.F. A role for brain stress systems in addiction. Neuron, 2008, 59, 11-34.
17. Koob, G.; Kreek, M.J. Stress, dysregulation of drug reward pathways, and the transition to drug dependence. Am. J. Psychiatry, 2007, 164, 1149-1159.
18. Li, Z.; Kang, S.S.; Lee, S.; Rivier, C. Effect of ethanol on the regulation of corticotropin-releasing factor (CRF) gene expression. Mol. Cell. Neurosci., 2005, 29, 345-354.
19. Redei, E.; Branch, B.J.; Gholami, S.; Lin, E.Y.; Taylor, A.N. Effects of ethanol on CRF release in vitro. Endocrinology, 1988, 123, 2736-2743.
20. Lee, S.; Selvage, D.; Hansen, K.; Rivier, C. Site of action of acute alcohol administration in stimulating the rat hypothalamic-pituitary-adrenal axis: comparison between the effect of systemic and intracerebroventricular injection of this drug on pituitary and hypothalamic responses. Endocrinology, 2004, 145, 4470-4479.
21. Rivier, C.; Lee, S. Acute alcohol administration stimulates the activity of hypothalamic neurons that express corticotropin-releasing factor and vasopressin. Brain Res., 1996, 726, 1-10.
22. Li, W.; Challis, J.R. Corticotropin-releasing hormone and urocortin induce secretion of matrix metalloproteinase-9 (MMP-9) without change in tissue inhibitors of MMP-1 by cultured cells from human placenta and fetal membranes. J. Clin. Endocrinol. Metab., 2005, 90, 6569-6574.
23. Lee, S.; Rivier, C. Alcohol increases the expression of type 1, but not type 2 alpha corticotropin-releasing factor (CRF) receptor messenger ribonucleic acid in the rat hypothalamus. Mol. Brain. Res., 1997, 52, 78-89.
24. Weitemier, A.Z.; Ryabinin, A.E. Brain region-specific regulation of urocortin 1 innervation and corticotropin-releasing factor receptor type 2 binding by ethanol exposure. Alcohol. Clin. Exp. Res., 2005, 29, 1610-1620.
25. Pich, E.M.; Lorang, M.; Yeganeh, M.; Rodriguez, d. F.; Raber, J.; Koob, G.F.; Weiss, F. Increase of extracellular corticotropin-releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis. J. Neurosci., 1995, 15, 5439-5447.
26. Sommer, W.H.; Rimondini, R.; Hansson, A.C.; Hipskind, P.A.; Gehlert, D.R.; Barr, C.S.; Heilig, M. Upregulation of voluntary alcohol intake, behavioral sensitivity to stress, and amygdala Crhr1 expression following a history of dependence. Biol. Psychiatry, 2008, 63(2), 139-145.
27. Funk, C.K.; O'Dell, L.E.; Crawford, E.F.; Koob, G.F. Corticotropin- releasing factor within the central nucleus of the amygdala mediates enhanced ethanol self-administration in withdrawn, ethanol-dependent rats. J. Neurosci., 2006, 26, 11324-11332.
28. Lack, A.K.; Floyd, D.W.; McCool, B.A. Chronic ethanol ingestion modulates proanxiety factors expressed in rat central amygdala. Alcohol, 2005, 36, 83-90.
29. Olive, M.F.; Koenig, H.N.; Nannini, M.A.; Hodge, C.W. Elevated extracellular CRF levels in the bed nucleus of the stria terminalis during ethanol withdrawal and reduction by subsequent ethanol intake. Pharmacol. Biochem. Behav., 2002, 72, 213-220.
30. Oliva, J.M.; Manzanares, J. Gene transcription alterations associated with decrease of ethanol intake induced by naltrexone in the brain of wistar rats. Neuropsychopharmacology, 2007, 32, 1358-1369.
31. Rivier, C.; Imaki, T.; Vale, W. Prolonged exposure to alcohol: effect on CRF mRNA levels, and CRF- and stress-induced ACTH secretion in the rat. Brain Res., 1990, 520, 1-5.
32. Pickering, C.; Avesson, L.; Liljequist, S.; Lindblom, J.; Schioth, H.B. The role of hypothalamic peptide gene expression in alcohol self-administration behavior. Peptides, 2007, 28, 2361-2371.
33. Francesconi, W.; Berton, F.; Repunte-Canonigo, V.; Hagihara, K.; Thurbon, D.; Lekic, D.; Specio, S.E.; Greenwell, T.N.; Chen, S.A.; Rice, K.C.; Richardson, H.N.; O'Dell, L.E.; Zorrilla, E.P.; Morales, M.; Koob, G.F.; Sanna, P.P. Protracted withdrawal from alcohol and drugs of abuse impairs long-term potentiation of intrinsic excitability in the juxtacapsular bed nucleus of the stria terminalis. J. Neurosci., 2009, 29, 5389-5401.
34. Valdez, G.R.; Roberts, A.J.; Chan, K.; Davis, H.; Brennan, M.; Zorrilla, E.P.; Koob, G.F. Increased ethanol self-administration and anxiety-like behavior during acute ethanol withdrawal and protracted abstinence: regulation by corticotropin-releasing factor. Alcohol. Clin. Exp. Res., 2002, 26, 1494-1501.
35. Falco, A.M.; Bergstrom, H.C.; Bachus, S.E.; Smith, R.F. Persisting changes in basolateral amygdala mRNAs after chronic ethanol consumption. Physiol. Behav., 2009, 96, 169-173.
36. Zhang, Z.; Morse, A.C.; Koob, G.F.; Schulteis, G. Dose- and time-dependent expression of anxiety-like behavior in the elevated plus-maze during withdrawal from acute and repeated intermittent ethanol intoxication in rats. Alcohol. Clin. Exp. Res., 2007, 31, 1811-1819.
37. Valdez, G.R.; Zorrilla, E.P.; Roberts, A.J.; Koob, G.F. Antagonism of corticotropin-releasing factor attenuates the enhanced responsiveness to stress observed during protracted ethanol abstinence. Alcohol, 2003, 29, 55-60.
38. Finn, D.A.; Snelling, C.; Fretwell, A.M.; Tanchuck, M.A.; Underwood, L.; Cole, M.; Crabbe, J.C.; Roberts, A.J. Increased drinking during withdrawal from intermittent ethanol exposure is blocked by the CRF receptor antagonist d-Phe-CRF(12-41). Alcohol. Clin. Exp. Res., 2007, 31, 939-949.
39. O'Callaghan, M.J.; Croft, A.P.; Jacquot, C.; Little, H.J. The hypothalamopituitary-adrenal axis and alcohol preference. Brain Res. Bull., 2005, 68, 171-178.
40. Richardson, H.N.; Zhao, Y.; Fekete, E.M.; Funk, C.K.; Wirsching, P.; Janda, K.D.; Zorrilla, E.P.; Koob, G.F. MPZP: a novel small molecule corticotropin-releasing factor type 1 receptor (CRF1) antagonist. Pharmacol. Biochem. Behav., 2008, 88, 497-510.
41. Gehlert, D.R.; Cippitelli, A.; Thorsell, A.; Le, A.D.; Hipskind, P.A.; Hamdouchi, C.; Lu, J.; Hembre, E.J.; Cramer, J.; Song, M.; McKinzie, D.; Morin, M.; Ciccocioppo, R.; Heilig, M. 3-(4-Chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1- ethylpropyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine: a novel brain-penetrant, orally available corticotropin-releasing factor receptor 1 antagonist with efficacy in animal models of alcoholism. J. Neurosci., 2007, 27, 2718-2726.
42. Sabino, V.; Cottone, P.; Koob, G.F.; Steardo, L.; Lee, M.J.; Rice, K.C.; Zorrilla, E.P. Dissociation between opioid and CRF1 antagonist sensitive drinking in Sardinian alcohol-preferring rats. Psychopharmacology (Berl), 2006, 189, 175-186.
43. Rhodes, J.S.; Best, K.; Belknap, J.K.; Finn, D.A.; Crabbe, J.C. Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice. Physiol. Behav., 2005, 84, 53-63.
44. Rhodes, J.S.; Ford, M.M.; Yu, C.H.; Brown, L.L.; Finn, D.A.; Garland, T., Jr.; Crabbe, J.C. Mouse inbred strain differences in ethanol drinking to intoxication. Genes Brain Behav., 2007, 6, 1-18.
45. Sparta, D.R.; Sparrow, A.M.; Lowery, E.G.; Fee, J.R.; Knapp, D.J.; Thiele, T.E. Blockade of the corticotropin releasing factor type 1 receptor attenuates elevated ethanol drinking associated with drinking in the dark procedures. Alcohol. Clin. Exp. Res., 2008, 32, 259-265.
46. Lyons, A.M.; Lowery, E.G.; Sparta, D.R.; Thiele, T.E. Effects of food availability and administration of orexigenic and anorectic agents on elevated ethanol drinking associated with drinking in the dark procedures. Alcohol. Clin. Exp. Res., 2008, 32, 1962-1968.
47. Lowery, E.G.; Spanos, M.; Navarro, M.; Lyons, A.M.; Hodge, C.W.; Thiele, T.E. CRF-1 antagonist and CRF-2 agonist decrease binge-like ethanol drinking in C57BL/6J mice independent of the HPA axis. Neuropsychopharmacology, 2009, (in press).
48. Ryabinin, A.E.; Yoneyama, N.; Tanchuck, M.A.; Mark, G.P.; Finn, D.A. Urocortin 1 microinjection into the mouse lateral septum regulates the acquisition and expression of alcohol consumption. Neuroscience, 2008, 151, 780-790.
49. Sharpe, A.L.; Phillips, T.J. Central urocortin 3 administration decreases limited-access ethanol intake in nondependent mice. Behav. Pharmacol., 2009, 20, 346-351.
50. Ji, D.; Gilpin, N.W.; Richardson, H.N.; Rivier, C.L.; Koob, G.F. Effects of naltrexone, duloxetine, and a corticotropin-releasing factor type 1 receptor antagonist on binge-like alcohol drinking in rats. Behav. Pharmacol., 2008, 19, 1-12.
51. Thorsell, A.; Slawecki, C.J.; Ehlers, C.L. Effects of neuropeptide Y and corticotropin-releasing factor on ethanol intake in Wistar rats: interaction with chronic ethanol exposure. Behav. Brain Res., 2005, 161, 133-140.
52. Bell, S.M.; Reynolds, J.G.; Thiele, T.E.; Gan, J.; Figlewicz, D.P.; Woods, S.C. Effects of third intracerebroventricular injections of corticotropin-releasing factor (CRF) on ethanol drinking and food intake. Psychopharmacology (Berl), 1998, 139, 128-135.
53. Campbell, B.M.; Morrison, J.L.; Walker, E.L.; Merchant, K.M. Differential regulation of behavioral, genomic, and neuroendocrine responses by CRF infusions in rats. Pharmacol. Biochem. Behav., 2004, 77, 447-455.
54. Lowery, E.G.; Sparrow, A.M.; Breese, G.R.; Knapp, D.J.; Thiele, T.E. The CRF-1 receptor antagonist, CP-154,526, attenuates stress-induced increases in ethanol consumption by BALB/cJ mice. Alcohol. Clin. Exp. Res., 2008, 32, 240-248.
55. 1 receptor antagonist antalarmin attenuates yohimbine-induced increases in operant alcohol self-administration and reinstatement of alcohol seeking in rats. Psychopharmacology (Berl), 2007, 195, 345-355.
56. Lodge, D.J.; Lawrence, A.J. The CRF1 receptor antagonist antalarmin reduces volitional ethanol consumption in isolation-reared fawn-hooded rats. Neuroscience, 2003, 117, 243-247.
57. Yang, X.; Wang, S.; Rice, K.C.; Munro, C.A.; Wand, G.S. Restraint stress and ethanol consumption in two mouse strains. Alcohol. Clin. Exp. Res., 2008, 32, 840-852.
58. Chu, K.; Koob, G.F.; Cole, M.; Zorrilla, E.P.; Roberts, A.J. Dependence-induced increases in ethanol self-administration in mice are blocked by the CRF1 receptor antagonist antalarmin and by CRF1 receptor knockout. Pharmacol. Biochem. Behav., 2007, 86, 813-821.
59. Gilpin, N.W.; Richardson, H.N.; Koob, G.F. Effects of CRF1-receptor and opioid-receptor antagonists on dependence-induced increases in alcohol drinking by alcohol-preferring (P) rats. Alcohol. Clin. Exp. Res., 2008, 32, 1535-1542.
60. Funk, C.K.; Zorrilla, E.P.; Lee, M.J.; Rice, K.C.; Koob, G.F. Corticotropin-releasing factor 1 antagonists selectively reduce ethanol self-administration in ethanol-dependent rats. Biol. Psychiatry, 2007, 61, 78-86.
61. Valdez, G.R.; Sabino, V.; Koob, G.F. Increased anxiety-like behavior and ethanol self-administration in dependent rats: reversal via corticotropin- releasing factor-2 receptor activation. Alcohol. Clin. Exp. Res., 2004, 28, 865-872.
62. 2 agonist administered into the central nucleus of the amygdala decreases ethanol self-administration in ethanol-dependent rats. Brain Res., 2007, 1155, 172-178.
63. Ciccocioppo, R.; Economidou, D.; Cippitelli, A.; Cucculelli, M.; Ubaldi, M.; Soverchia, L.; Lourdusamy, A.; Massi, M. Genetically selected Marchigian Sardinian alcohol-preferring (msP) rats: an animal model to study the neurobiology of alcoholism. Addict. Biol., 2006, 11, 339-355.
64. Hansson, A.C.; Cippitelli, A.; Sommer, W.H.; Fedeli, A.; Bjork, K.; Soverchia, L.; Terasmaa, A.; Massi, M.; Heilig, M.; Ciccocioppo, R. Variation at the rat Crhr1 locus and sensitivity to relapse into alcohol seeking induced by environmental stress. Proc. Natl. Acad. Sci. USA, 2006, 103, 15236-15241.
65. Koob, G.F. Animal models of craving for ethanol. Addiction, 2000, 95(Suppl 2), S73-S81.
66. Le, A.; Shaham, Y. Neurobiology of relapse to alcohol in rats. Pharmacol. Ther., 2002, 94, 137-156.
67. Le, A.D.; Kiianmaa, K.; Cunningham, C.L.; Engel, J.A.; Ericson, M.; Soderpalm, B.; Koob, G.F.; Roberts, A.J.; Weiss, F.; Hyytia, P.; Janhunen, S.; Mikkola, J.; Backstrom, P.; Ponomarev, I.; Crabbe, J.C. Neurobiological processes in alcohol addiction. Alcohol. Clin. Exp. Res., 2001, 25, 144S-151S.
68. Weiss, F.; Ciccocioppo, R.; Parsons, L.H.; Katner, S.; Liu, X.; Zorrilla, E.P.; Valdez, G.R.; Ben-Shahar, O.; Angeletti, S.; Richter, R.R. Compulsive drug-seeking behavior and relapse. Neuroadaptation, stress, and conditioning factors. Ann. NY Acad. Sci., 2001, 937, 1-26.
69. Le, A.D.; Harding, S.; Juzytsch, W.; Watchus, J.; Shalev, U.; Shaham, Y. The role of corticotropin-releasing factor in stress-induced relapse to alcohol-seeking behavior in rats. Psychopharmacology (Berl), 2000, 150, 317-324.
70. Liu, X.; Weiss, F. Additive effect of stress and drug cues on reinstatement of ethanol seeking: exacerbation by history of dependence and role of concurrent activation of corticotropin-releasing factor and opioid mechanisms. J. Neurosci., 2002, 22, 7856-7861.
71. Le, A.D.; Harding, S.; Juzytsch, W.; Fletcher, P.J.; Shaham, Y. The role of corticotropin-releasing factor in the median raphe nucleus in relapse to alcohol. J. Neurosci., 2002, 22, 7844-7849.
72. Colombo, G.; Lobina, C.; Carai, M.A.; Gessa, G.L. Phenotypic characterization of genetically selected Sardinian alcohol-preferring (sP) and -non-preferring (sNP) rats. Addict. Biol., 2006, 11, 324-338.
73. Bell, R.L.; Rodd, Z.A.; Lumeng, L.; Murphy, J.M.; McBride, W.J. The alcohol-preferring P rat and animal models of excessive alcohol drinking. Addict. Biol., 2006, 11, 270-288.
74. Rodd, Z.A.; Bell, R.L.; Sable, H.J.; Murphy, J.M.; McBride, W.J. Recent advances in animal models of alcohol craving and relapse. Pharmacol. Biochem. Behav., 2004, 79, 439-450.
75. Sparta, D.R.; Ferraro, F.M., 3rd; Fee, J.R.; Knapp, D.J.; Breese, G.R.; Thiele, T.E. The alcohol deprivation effect in C57BL/6J mice is observed using operant self-administration procedures and is modulated by CRF-1 receptor signaling. Alcohol. Clin. Exp. Res., 2009, 33, 31-42.
76. Overstreet, D.H.; Knapp, D.J.; Breese, G.R. Drug challenges reveal differences in mediation of stress facilitation of voluntary alcohol drinking and withdrawal-induced anxiety in alcohol-preferring P rats. Alcohol. Clin. Exp. Res., 2007, 31, 1473-1481.
77. Overstreet, D.H.; Knapp, D.J.; Breese, G.R. Modulation of multiple ethanol withdrawal-induced anxiety-like behavior by CRF and CRF1 receptors. Pharmacol. Biochem. Behav., 2004, 77, 405-413.
78. Zorrilla, E.P.; Valdez, G.R.; Weiss, F. Changes in levels of regional CRF-like-immunoreactivity and plasma corticosterone during protracted drug withdrawal in dependent rats. Psychopharmacology (Berl), 2001, 158, 374-381.
79. Baldwin, H.A.; Rassnick, S.; Rivier, J.; Koob, G.F.; Britton, T.K. CRF antagonist reverses the "anxiogenic" response to ethanol withdrawal in the rat. Psychopharmacology (Berl), 1991, 103, 227-232.
80. Rassnick, S.; Heinrichs, S.C.; Britton, K.T.; Koob, G.F. Microinjection of a corticotropin-releasing factor antagonist into the central nucleus of the amygdala reverses anxiogenic-like effects of ethanol withdrawal. Brain Res., 1993, 605, 25-32.
81. Wills, T.A.; Knapp, D.J.; Overstreet, D.H.; Breese, G.R. Sensitization, duration, and pharmacological blockade of anxiety-like behavior following repeated ethanol withdrawal in adolescent and adult rats. Alcohol. Clin. Exp. Res., 2009, 33, 455-463.
82. Overstreet, D.H.; Knapp, D.J.; Breese, G.R. Pharmacological modulation of repeated ethanol withdrawal-induced anxiety-like behavior differs in alcohol-preferring P and Sprague-Dawley rats. Pharmacol. Biochem. Behav., 2005, 81, 122-130.
83. Breese, G.R.; Knapp, D.J.; Overstreet, D.H. Stress sensitization of ethanol withdrawal-induced reduction in social interaction: inhibition by CRF-1 and benzodiazepine receptor antagonists and a 5-HT1A-receptor agonist. Neuropsychopharmacology, 2004, 29, 470-482.
84. Breese, G.R.; Overstreet, D.H.; Knapp, D.J.; Navarro, M. Prior multiple ethanol withdrawals enhance stress-induced anxiety-like behavior: inhibition by CRF1- and benzodiazepine-receptor antagonists and a 5-HT1A-receptor agonist. Neuropsychopharmacology, 2005, 30, 1662-1669.
85. Knapp, D.J.; Overstreet, D.H.; Moy, S.S.; Breese, G.R. SB242084, flumazenil, and CRA1000 block ethanol withdrawal-induced anxiety in rats. Alcohol, 2004, 32, 101-111.
86. Koob, G.F.; Le Moal, M. Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology, 2001, 24, 97-129.
87. Koob, G.F.; Le Moal, M. Review: neurobiological mechanisms for opponent motivational processes in addiction. Phil. Trans. R. Soc. Lond., 2008, 363, 3113-3123.
88. Treutlein, J.; Kissling, C.; Frank, J.; Wiemann, S.; Dong, L.; Depner, M.; Saam, C.; Lascorz, J.; Soyka, M.; Preuss, U.W.; Rujescu, D.; Skowronek, M.H.; Rietschel, M.; Spanagel, R.; Heinz, A.; Laucht, M.; Mann, K.; Schumann, G. Genetic association of the human corticotropin releasing hormone receptor 1 (CRHR1) with binge drinking and alcohol intake patterns in two independent samples. Mol. Psychiatry, 2006, 11, 594-602.
89. Bonomo, Y.A.; Bowes, G.; Coffey, C.; Carlin, J.B.; Patton, G.C. Teenage drinking and the onset of alcohol dependence: a cohort study over seven years. Addiction, 2004, 99, 1520-1528.
90. Jennison, K.M. The short-term effects and unintended long-term consequences of binge drinking in college: a 10-year follow-up study. Am. J. Drug Alcohol Abuse, 2004, 30, 659-684.
91. Arborelius, L.; Owens, M.J.; Plotsky, P.M.; Nemeroff, C.B. The role of corticotropin-releasing factor in depression and anxiety disorders. J. Endocrinol., 1999, 160, 1-12.
92. Heinrichs, S.C.; Richard, D. The role of corticotropin-releasing factor and urocortin in the modulation of ingestive behavior. Neuropeptides, 1999, 33, 350-359.
93. Smith, S.M.; Vale, W.W. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin. Neurosci., 2006, 8, 383-395.
94. Menzaghi, F.; Rassnick, S.; Heinrichs, S.; Baldwin, H.; Pich, E.M.; Weiss, F.; Koob, G.F. The role of corticotropin-releasing factor in the anxiogenic effects of ethanol withdrawal. Ann. NY Acad. Sci., 1994, 739, 176-184.
95. Kehne, J.H. The CRF1 receptor, a novel target for the treatment of depression, anxiety, and stress-related disorders. CNS Neurol. Disord. Drug Targets, 2007, 6, 163-182.
96. Kuperman, Y.; Chen, A. Urocortins: emerging metabolic and energy homeostasis perspectives. Trends Endocrinol. Metab., 2008, 19, 122-129.
97. Ryabinin, A.E.; Weitemier, A.Z. The urocortin 1 neurocircuit: ethanol-sensitivity and potential involvement in alcohol consumption. Brain Res. Rev., 2006, 52, 368-380.
98. Sanghvi, R.; Mogalian, E.; Machatha, S.G.; Narazaki, R.; Karlage, K.L.; Jain, P.; Tabibi, S.E.; Glaze, E.; Myrdal, P.B.; Yalkowsky, S.H. Preformulation and pharmacokinetic studies on antalarmin: a novel stress inhibitor. J. Pharm. Sci., 2009, 98, 205-214.
99. Gilligan, P.J.; He, L.; Clarke, T.; Tivitmahaisoon, P.; Lelas, S.; Li, Y.W.; Heman, K.; Fitzgerald, L.; Miller, K.; Zhang, G.; Marshall, A.; Krause, C.; McElroy, J.; Ward, K.; Shen, H.; Wong, H.; Grossman, S.; Nemeth, G.; Zaczek, R.; Arneric, S.P.; Hartig, P.; Robertson, D.W.; Trainor, G. 8-(4-Methoxyphenyl)pyrazolo[1,5-a]-1,3,5-triazines: selective and centrally active corticotropin-releasing factor receptor-1 (CRF1) antagonists. J. Med. Chem., 2009, 52, 3073-3083.
100. Gilligan, P.J.; Clarke, T.; He, L.; Lelas, S.; Li, Y.W.; Heman, K.; Fitzgerald, L.; Miller, K.; Zhang, G.; Marshall, A.; Krause, C.; McElroy, J.F.; Ward, K.; Zeller, K.; Wong, H.; Bai, S.; Saye, J.; Grossman, S.; Zaczek, R.; Arneric, S.P.; Hartig, P.; Robertson, D.; Trainor, G. Synthesis and structure-activity relationships of 8-(pyrid-3-yl)pyrazolo[1,5-a]-1,3,5- triazines: potent, orally bioavailable corticotropin releasing factor receptor-1 (CRF1) antagonists. J. Med. Chem., 2009, 52, 3084-3092.
101. Perrin, M.H.; Sutton, S.W.; Cervini, L.A.; Rivier, J.E.; Vale, W.W. Comparison of an agonist, urocortin, and an antagonist, astressin, as radioligands for characterization of corticotropin-releasing factor receptors. J. Pharmacol. Exp. Ther., 1999, 288, 729-734.
102. Perrin, M.H.; Vale, W.W. Corticotropin releasing factor receptors and their ligand family. Ann. N.Y. Acad. Sci., 1999, 885, 312-328.
103. Lewis, K.; Li, C.; Perrin, M.H.; Blount, A.; Kunitake, K.; Donaldson, C.; Vaughan, J.; Reyes, T.M.; Gulyas, J.; Fischer, W.; Bilezikjian, L.; Rivier, J.; Sawchenko, P.E.; Vale, W.W. Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor. Proc..Natl. Acad. Sci. USA, 2001, 98, 7570-7575.
104. Weitemier, A.Z.; Ryabinin, A.E. Urocortin 1 in the dorsal raphe regulates food and fluid consumption, but not ethanol preference in C57BL/6J mice. Neuroscience, 2006, 137, 1439-1445.
105. Zorrilla, E.P.; Schulteis, G.; Ormsby, A.; Klaassen, A.; Ling, N.; McCarthy, J.R.; Koob, G.F.; De Souza, E.B. Urocortin shares the memory modulating effects of corticotropin-releasing factor (CRF): mediation by CRF1 receptors. Brain Res., 2002, 952, 200-210.
106. Steckler, T.; Dautzenberg, F.M. Corticotropin-releasing factor receptor antagonists in affective disorders and drug dependence - an update. CNS Neurol. Disord. Drug Targets, 2006, 5, 147-165.
107. Valdez, G.R. Development of CRF1 receptor antagonists as antidepressants and anxiolytics: progress to date. CNS Drugs, 2006, 20, 887-896.
108. Hsin, L.W.; Tian, X.; Webster, E.L.; Coop, A.; Caldwell, T.M.; Jacobson, A.E.; Chrousos, G.P.; Gold, P.W.; Habib, K.E.; Ayala, A.; Eckelman, W.C.; Contoreggi, C.; Rice, K.C. CRHR1 receptor binding and lipophilicity of pyrrolopyrimidines, potential nonpeptide corticotropin-releasing hormone type 1 receptor antagonists. Bioorg. Med. Chem., 2002, 10, 175-183.
109. Rivier, J.; Gulyas, J.; Kirby, D.; Low, W.; Perrin, M.H.; Kunitake, K.; DiGruccio, M.; Vaughan, J.; Reubi, J.C.; Waser, B.; Koerber, S.C.; Martinez, V.; Wang, L.; Tache, Y.; Vale, W. Potent and long-acting corticotropin releasing factor (CRF) receptor 2 selective peptide competitive antagonists. J. Med. Chem., 2002, 45, 4737-4747.