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Role of Corticotropin-Releasing Factor in Drug Addiction

Potential for Pharmacological Intervention

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Abstract

Drug dependence is a chronically relapsing disorder that places an enormous strain on healthcare systems. For treatments to have long-term clinical value, they must address the causes of relapse. Corticotropin-releasing factor (CRF), a neuropeptide central to the stress response, may be one key to solving the relapse cycle. CRF is hypothesized to mediate the elevated anxiety and negative emotional states experienced during the development of dependence. This review summarizes existing data on changes in the CRF system produced by drugs of abuse and the function of CRF receptors in regulating behavioural responses to drugs of abuse, with an emphasis on drug dependence. Drug-induced changes in neuronal excitability throughout the limbic system, as well as the reversal of these neuroadaptations by CRF receptor antagonists, are also addressed. CRF receptor antagonists, by reducing the motivational effects of drug withdrawal and protracted abstinence, are proposed to be novel therapeutic targets for drug abuse and addiction.

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References

  1. Koob GF. A role for brain stress systems in addiction. Neuron 2008 Jul 10; 59(1): 11–34

    Article  PubMed  CAS  Google Scholar 

  2. Sinha R. Chronic stress, drug use, and vulnerability to addiction. Ann N Y Acad Sci 2008 Oct; 1141: 105–30

    Article  PubMed  CAS  Google Scholar 

  3. Goeders NE. The impact of stress on addiction. Eur Neuropsychopharmacol 2003 Dec; 13(6): 435–41

    Article  PubMed  CAS  Google Scholar 

  4. Weiss F, Ciccocioppo R, Parsons LH, et al. Compulsive drug-seeking behavior and relapse: neuroadaptation, stress, and conditioning factors. Ann N Y Acad Sci 2001 Jun; 937: 1–26

    Article  PubMed  CAS  Google Scholar 

  5. De Luca V, Tharmalingam S, Kennedy JL. Association study between the corticotropin-releasing hormone receptor 2 gene and suicidality in bipolar disorder. Eur Psychiatry 2007 Jul; 22(5): 282–7

    Article  PubMed  Google Scholar 

  6. Enoch MA, Shen PH, Ducci F, et al. Common genetic origins for EEG, alcoholism and anxiety: the role of CRH-BP. PLoS One 2008; 3(10): e3620

    Article  PubMed  CAS  Google Scholar 

  7. Clarke TK, Schumann G. Gene-environment interactions resulting in risk alcohol drinking behaviour are mediated by CRF and CRF1. Pharmacol Biochem Behav 2009 Sep; 93(3): 230–6

    Article  PubMed  CAS  Google Scholar 

  8. Blomeyer D, Treutlein J, Esser G, et al. Interaction between CRHR1 gene and stressful life events predicts adolescent heavy alcohol use. Biol Psychiatry 2008 Jan 15; 63(2): 146–51

    Article  PubMed  CAS  Google Scholar 

  9. Treutlein J, Kissling C, Frank J, et al. 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 Jun; 11(6): 594–602

    Article  PubMed  CAS  Google Scholar 

  10. Spiess J, Rivier J, Rivier C, et al. Primary structure of corticotropin-releasing factor from ovine hypothalamus. Proc Natl Acad Sci U S A 1981 Oct; 78(10): 6517–21

    Article  PubMed  CAS  Google Scholar 

  11. Chang CP, Pearse 2nd RV, O’Connell S, et al. Identification of a seven transmembrane helix receptor for corticotropin-releasing factor and sauvagine in mammalian brain. Neuron 1993 Dec; 11(6): 1187–95

    Article  PubMed  CAS  Google Scholar 

  12. Lovenberg TW, Liaw CW, Grigoriadis DE, et al. Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain. Proc Natl Acad Sci U S A 1995 Jan 31; 92(3): 836–40

    Article  PubMed  CAS  Google Scholar 

  13. Grammatopoulos DK, Randeva HS, Levine MA, et al. Rat cerebral cortex corticotropin-releasing hormone receptors: evidence for receptor coupling to multiple G-proteins. J Neurochem 2001 Jan; 76(2): 509–19

    Article  PubMed  CAS  Google Scholar 

  14. Blank T, Nijholt I, Grammatopoulos DK, et al. Corticotropin-releasing factor receptors couple to multiple G-proteins to activate diverse intracellular signaling pathways in mouse hippocampus: role in neuronal excitability and associative learning. J Neurosci 2003 Jan 15; 23(2): 700–7

    PubMed  CAS  Google Scholar 

  15. Linton EA, Behan DP, Saphier PW, et al. Corticotropin-releasing hormone (CRH)-binding protein: reduction in the adrenocorticotropin-releasing activity of placental but not hypothalamic CRH. J Clin Endocrinol Metab 1990 Jun; 70(6): 1574–80

    Article  PubMed  CAS  Google Scholar 

  16. Guillemin R, Dear WE, Nichols Jr B, et al. ACTH releasing activity in vivo of a CRF preparation and lysine vasopressin. Proc Soc Exp Biol Med 1959 May; 101(1): 107–11

    PubMed  CAS  Google Scholar 

  17. Hiroshige T, Ogura C, Itoh S. ACTH release by purified hypothalamic CRF preparation as assayed by intrapituitary microinjection. Endocrinol Jpn 1968 Sep; 15(3): 379–82

    Article  PubMed  CAS  Google Scholar 

  18. McEwen BS. Influences of adrenocortical hormones on pituitary and brain function. Monogr Endocrinol 1979; 12: 467–92

    Article  PubMed  CAS  Google Scholar 

  19. Kretz O, Reichardt HM, Schutz G, et al. Corticotropin-releasing hormone expression is the major target for glucocorticoid feedback-control at the hypothalamic level. Brain Res 1999 Feb 13; 818(2): 488–91

    Article  PubMed  CAS  Google Scholar 

  20. Heinrichs SC, Menzaghi F, Merlo Pich E, et al. The role of CRF in behavioral aspects of stress. Ann N Y Acad Sci 1995 Dec 29; 771: 92–104

    Article  PubMed  CAS  Google Scholar 

  21. Pilcher WH, Joseph SA. Co-localization of CRF-ir perikarya and ACTH-ir fibers in rat brain. Brain Res 1984 May 7; 299(1): 91–102

    Article  PubMed  CAS  Google Scholar 

  22. Melia KR, Sananes CB, Davis M. Lesions of the central nucleus of the amygdala block the excitatory effects of septal ablation on the acoustic startle reflex. Physiol Behav 1992 Jan; 51(1): 175–80

    Article  PubMed  CAS  Google Scholar 

  23. Day HE, Nebel S, Sasse S, et al. Inhibition of the central extended amygdala by loud noise and restraint stress. Eur J Neurosci 2005 Jan; 21(2): 441–54

    Article  PubMed  Google Scholar 

  24. Hammack SE, Richey KJ, Watkins LR, et al. Chemical lesion of the bed nucleus of the stria terminalis blocks the behavioral consequences of uncontrollable stress. Behav Neurosci 2004 Apr; 118(2): 443–8

    Article  PubMed  Google Scholar 

  25. Koob GF. Corticotropin-releasing factor, norepinephrine, and stress. Biol Psychiatry 1999 Nov 1; 46(9): 1167–80

    Article  PubMed  CAS  Google Scholar 

  26. Potter E, Behan DP, Linton EA, et al. The central distribution of a corticotropin-releasing factor (CRF)-binding protein predicts multiple sites and modes of interaction with CRF. Proc Natl Acad Sci U S A 1992 May 1; 89(9): 4192–6

    Article  PubMed  CAS  Google Scholar 

  27. De Souza EB, Battaglia G. Corticotropin-releasing hormone (CRH) receptors in brain. Adv Exp Med Biol 1988; 245: 123–36

    PubMed  Google Scholar 

  28. Swinny JD, Kalicharan D, Blaauw EH, et al. Corticotropin-releasing factor receptor types 1 and 2 are differentially expressed in pre- and post-synaptic elements in the post-natal developing rat cerebellum. Eur J Neurosci 2003 Aug; 18(3): 549–62

    Article  PubMed  CAS  Google Scholar 

  29. Schierloh A, Deussing J, Wurst W, et al. Corticotropin-releasing factor (CRF) receptor type 1-dependent modulation of synaptic plasticity. Neurosci Lett 2007 Apr 6; 416(1): 82–6

    Article  PubMed  CAS  Google Scholar 

  30. 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 Apr 9; 28(15): 3861–76

    Article  PubMed  CAS  Google Scholar 

  31. Miyata M, Okada D, Hashimoto K, et al. Corticotropin-releasing factor plays a permissive role in cerebellar long-term depression. Neuron 1999 Apr; 22(4): 763–75

    Article  PubMed  CAS  Google Scholar 

  32. Rainnie DG, Bergeron R, Sajdyk TJ, et al. Corticotrophin releasing factor-induced synaptic plasticity in the amygdala translates stress into emotional disorders. J Neurosci 2004 Apr 7; 24(14): 3471–9

    Article  PubMed  CAS  Google Scholar 

  33. Schmolesky MT, De Ruiter MM, De Zeeuw CI, et al. The neuropeptide corticotropin-releasing factor regulates excitatory transmission and plasticity at the climbing fibre-Purkinje cell synapse. Eur J Neurosci 2007 Mar; 25(5): 1460–6

    Article  PubMed  CAS  Google Scholar 

  34. Gallagher JP, Orozco-Cabal LF, Liu J, et al. Synaptic physiology of central CRH system. Eur J Pharmacol 2008 Apr 7; 583(2–3): 215–25

    Article  PubMed  CAS  Google Scholar 

  35. Van Pett K, Viau V, Bittencourt JC, et al. Distribution of mRNAs encoding CRF receptors in brain and pituitary of rat and mouse. J Comp Neurol 2000 Dec 11; 428(2): 191–212

    Article  PubMed  Google Scholar 

  36. Potter E, Sutton S, Donaldson C, et al. Distribution of corticotropin-releasing factor receptor mRNA expression in the rat brain and pituitary. Proc Natl Acad Sci U S A 1994 Sep 13; 91(19): 8777–81

    Article  PubMed  CAS  Google Scholar 

  37. Chalmers DT, Lovenberg TW, De Souza EB. Localization of novel corticotropin-releasing factor receptor (CRF2) mRNA expression to specific subcortical nuclei in rat brain: comparison with CRF1 receptor mRNA expression. J Neurosci 1995 Oct; 15(10): 6340–50

    PubMed  CAS  Google Scholar 

  38. Timpl P, Spanagel R, Sillaber I, et al. Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor 1. Nat Genet 1998 Jun; 19(2): 162–6

    Article  PubMed  CAS  Google Scholar 

  39. Muller MB, Zimmermann S, Sillaber I, et al. Limbic corticotropin-releasing hormone receptor 1 mediates anxiety-related behavior and hormonal adaptation to stress. Nat Neurosci 2003 Oct; 6(10): 1100–7

    Article  PubMed  CAS  Google Scholar 

  40. Bale TL, Contarino A, Smith GW, et al. Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress. Nat Genet 2000 Apr; 24(4): 410–4

    Article  PubMed  CAS  Google Scholar 

  41. Kishimoto T, Radulovic J, Radulovic M, et al. Deletion of crhr2 reveals an anxiolytic role for corticotropin-releasing hormone receptor-2. Nat Genet 2000 Apr; 24(4): 415–9

    Article  PubMed  CAS  Google Scholar 

  42. Coste SC, Kesterson RA, Heldwein KA, et al. Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2. Nat Genet 2000 Apr; 24(4): 403–9

    Article  PubMed  CAS  Google Scholar 

  43. Coste SC, Heard AD, Phillips TJ, et al. Corticotropin-releasing factor receptor type 2-deficient mice display impaired coping behaviors during stress. Genes Brain Behav 2006 Mar; 5(2): 131–8

    Article  PubMed  CAS  Google Scholar 

  44. Buckingham JC. Secretion of corticotrophin and its hypothalamic releasing factor in response to morphine and opioid peptides. Neuroendocrinology 1982; 35(2): 111–6

    Article  PubMed  CAS  Google Scholar 

  45. Swerdlow NR, Koob GF, Cador M, et al. Pituitary-adrenal axis responses to acute amphetamine in the rat. Pharmacol Biochem Behav 1993 Jul; 45(3): 629–37

    Article  PubMed  CAS  Google Scholar 

  46. Calogero AE, Gallucci WT, Kling MA, et al. Cocaine stimulates rat hypothalamic corticotropin-releasing hormone secretion in vitro. Brain Res 1989 Dec 25; 505(1): 7–11

    Article  PubMed  CAS  Google Scholar 

  47. Buckingham JC, Hodges JR. Hypothalamic receptors influencing the secretion of corticotrophin releasing hormone in the rat. J Physiol 1979 May; 290(2): 421–31

    PubMed  CAS  Google Scholar 

  48. Weidenfeld J, Feldman S, Mechoulam R. Effect of the brain constituent anandamide, a cannabinoid receptor agonist, on the hypothalamo-pituitary-adrenal axis in the rat. Neuroendocrinology 1994 Feb; 59(2): 110–2

    Article  PubMed  CAS  Google Scholar 

  49. Rivier C, Bruhn T, Vale W. Effect of ethanol on the hypothalamic-pituitary-adrenal axis in the rat: role of corticotropin-releasing factor (CRF). J Pharmacol Exp Ther 1984 Apr; 229(1): 127–31

    PubMed  CAS  Google Scholar 

  50. Rivier CL, Grigoriadis DE, Rivier JE. Role of corticotropin-releasing factor receptors type 1 and 2 in modulating the rat adrenocorticotropin response to stressors. Endocrinology 2003 Jun; 144(6): 2396–403

    Article  PubMed  CAS  Google Scholar 

  51. Sarnyai Z, Biro E, Penke B, et al. The cocaine-induced elevation of plasma corticosterone is mediated by endogenous corticotropin-releasing factor (CRF) in rats. Brain Res 1992 Aug 28; 589(1): 154–6

    Article  PubMed  CAS  Google Scholar 

  52. Cole BJ, Cador M, Stinus L, et al. Critical role of the hypothalamic pituitary adrenal axis in amphetamine-induced sensitization of behavior. Life Sci 1990; 47(19): 1715–20

    Article  PubMed  CAS  Google Scholar 

  53. Fee JR, Sparta DR, Picker MJ, et al. Corticotropin releasing factor-1 receptor antagonist, CP-154,526, blocks the expression of ethanol-induced behavioral sensitization in DBA/2J mice. Neuroscience 2007 Nov 30; 150(1): 14–21

    Article  PubMed  CAS  Google Scholar 

  54. Przegalinski E, Filip M, Frankowska M, et al. Effects of CP 154,526, a CRF1 receptor antagonist, on behavioral responses to cocaine in rats. Neuropeptides 2005 Oct; 39(5): 525–33

    Article  PubMed  CAS  Google Scholar 

  55. Pastor R, McKinnon CS, Scibelli AC, et al. Corticotropin-releasing factor-1 receptor involvement in behavioral neuroadaptation to ethanol: a urocortin1-independent mechanism. Proc Natl Acad Sci U S A 2008 Jul 1; 105(26): 9070–5

    Article  PubMed  CAS  Google Scholar 

  56. Goeders NE, Guerin GF. Effects of surgical and pharmacological adrenalectomy on the initiation and maintenance of intravenous cocaine self-administration in rats. Brain Res 1996 May 25; 722(1–2): 145–52

    Article  PubMed  CAS  Google Scholar 

  57. Koob GF. The role of CRF and CRF-related peptides in the dark side of addiction. Brain Res 2010 Feb 16; 1314: 3–14

    Article  PubMed  CAS  Google Scholar 

  58. Zhou Y, Spangler R, LaForge KS, et al. Corticotropin-releasing factor and type 1 corticotropin-releasing factor receptor messenger RNAs in rat brain and pituitary during ‘binge’-pattern cocaine administration and chronic withdrawal. J Pharmacol Exp Ther 1996 Oct; 279(1): 351–8

    PubMed  CAS  Google Scholar 

  59. Maj M, Turchan J, Smialowska M, et al. Morphine and cocaine influence on CRF biosynthesis in the rat central nucleus of amygdala. Neuropeptides 2003 Apr; 37(2): 105–10

    Article  PubMed  CAS  Google Scholar 

  60. Zorrilla EP, Valdez GR, Weiss F. Changes in levels of regional CRF-like-immunoreactivity and plasma corticosterone during protracted drug withdrawal in dependent rats. Psychopharmacology (Berl) 2001 Dec; 158(4): 374–81

    Article  CAS  Google Scholar 

  61. Zhou Y, Spangler R, Ho A, et al. Increased CRH mRNA levels in the rat amygdala during short-term withdrawal from chronic ‘binge’ cocaine. Brain Res Mol Brain Res 2003 May 26; 114(1): 73–9

    Article  PubMed  CAS  Google Scholar 

  62. Caberlotto L, Rimondini R, Hansson A, et al. Corticotropin-releasing hormone (CRH) mRNA expression in rat central amygdala in cannabinoid tolerance and withdrawal: evidence for an allostatic shift? Neuropsychopharmacology 2004 Jan; 29(1): 15–22

    Article  PubMed  CAS  Google Scholar 

  63. Sommer WH, Rimondini R, Hansson AC, et al. Upregulation of voluntary alcohol intake, behavioral sensitivity to stress, and amygdala crhr1 expression following a history of dependence. Biol Psychiatry 2008 Jan 15; 63(2): 139–45

    Article  PubMed  Google Scholar 

  64. George O, Ghozland S, Azar MR, et al. CRF-CRF1 system activation mediates withdrawal-induced increases in nicotine self-administration in nicotine-dependent rats. Proc Natl Acad Sci U S A 2007 Oct 23; 104(43): 17198–203

    Article  PubMed  CAS  Google Scholar 

  65. Koob G, Kreek MJ. Stress, dysregulation of drug reward pathways, and the transition to drug dependence. Am J Psychiatry 2007 Aug; 164(8): 1149–59

    Article  PubMed  Google Scholar 

  66. Richter RM, Weiss F. In vivo CRF release in rat amygdala is increased during cocaine withdrawal in self-administering rats. Synapse 1999 Jun 15; 32(4): 254–61

    PubMed  CAS  Google Scholar 

  67. Olive MF, Koenig HN, Nannini MA, et al. 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 May; 72(1–2): 213–20

    Article  PubMed  CAS  Google Scholar 

  68. Merlo Pich E, Lorang M, Yeganeh M, et al. 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 Aug; 15(8): 5439–47

    PubMed  CAS  Google Scholar 

  69. Rodriguez de Fonseca F, Carrera MR, Navarro M, et al. Activation of corticotropin-releasing factor in the limbic system during cannabinoid withdrawal. Science 1997 Jun 27; 276(5321): 2050–4

    Article  PubMed  CAS  Google Scholar 

  70. Sarnyai Z, Biro E, Gardi J, et al. Brain corticotropin-releasing factor mediates ‘anxiety-like’ behavior induced by cocaine withdrawal in rats. Brain Res 1995 Mar 27; 675(1–2): 89–97

    Article  PubMed  CAS  Google Scholar 

  71. Funk CK, O’Dell LE, Crawford EF, et al. Corticotropin-releasing factor within the central nucleus of the amygdala mediates enhanced ethanol self-administration in withdrawn, ethanol-dependent rats. J Neurosci 2006 Nov 1; 26(44): 11324–32

    Article  PubMed  CAS  Google Scholar 

  72. Iredale PA, Alvaro JD, Lee Y, et al. Role of corticotropin-releasing factor receptor-1 in opiate withdrawal. J Neurochem 2000 Jan; 74(1): 199–208

    Article  PubMed  CAS  Google Scholar 

  73. Chu K, Koob GF, Cole M, et al. 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 Apr; 86(4): 813–21

    Article  PubMed  CAS  Google Scholar 

  74. Contarino A, Papaleo F. The corticotropin-releasing factor receptor-1 pathway mediates the negative affective states of opiate withdrawal. Proc Natl Acad Sci U S A 2005 Dec 20; 102(51): 18649–54

    Article  PubMed  CAS  Google Scholar 

  75. Sharpe AL, Coste SC, Burkhart-Kasch S, et al. Mice deficient in corticotropin-releasing factor receptor type 2 exhibit normal ethanol-associated behaviors. Alcohol Clin Exp Res 2005 Sep; 29(9): 1601–9

    Article  PubMed  CAS  Google Scholar 

  76. Hansson AC, Cippitelli A, Sommer WH, et al. Variation at the rat Crhr1 locus and sensitivity to relapse into alcohol seeking induced by environmental stress. Proc Natl Acad Sci U S A 2006 Oct 10; 103(41): 15236–41

    Article  PubMed  CAS  Google Scholar 

  77. Papaleo F, Ghozland S, Ingallinesi M, et al. Disruption of the CRF(2) receptor pathway decreases the somatic expression of opiate withdrawal. Neuropsychopharmacology 2008 Nov; 33(12): 2878–87

    Article  PubMed  CAS  Google Scholar 

  78. Papaleo F, Kitchener P, Contarino A. Disruption of the CRF/CRF1 receptor stress system exacerbates the somatic signs of opiate withdrawal. Neuron 2007 Feb 15; 53(4): 577–89

    Article  PubMed  CAS  Google Scholar 

  79. Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Methods 2000 Jul–Aug; 44(1): 235–49

    Article  PubMed  CAS  Google Scholar 

  80. Zhao H. Lead optimization in the nondrug-like space. Drug Discov Today 2011 Feb; 16(3–4): 158–63

    Article  PubMed  Google Scholar 

  81. Curtis AL, Grigoriadis DE, Page ME, et al. Pharmacological comparison of two corticotropin-releasing factor antagonists: in vivo and in vitro studies. J Pharmacol Exp Ther 1994 Jan; 268(1): 359–65

    PubMed  CAS  Google Scholar 

  82. Webster EL, Lewis DB, Torpy DJ, et al. In vivo and in vitro characterization of antalarmin, a nonpeptide corticotropin-releasing hormone (CRH) receptor antagonist: suppression of pituitary ACTH release and peripheral inflammation. Endocrinology 1996 Dec; 137(12): 5747–50

    Article  PubMed  CAS  Google Scholar 

  83. Keller C, Bruelisauer A, Lemaire M, et al. Brain pharmacokinetics of a nonpeptidic corticotropin-releasing factor receptor antagonist. Drug Metab Dispos 2002 Feb; 30(2): 173–6

    Article  PubMed  CAS  Google Scholar 

  84. Lundkvist J, Chai Z, Teheranian R, et al. A non peptidic corticotropin releasing factor receptor antagonist attenuates fever and exhibits anxiolytic-like activity. Eur J Pharmacol 1996 Aug 8; 309(2): 195–200

    Article  PubMed  CAS  Google Scholar 

  85. Chen C, Wilcoxen KM, Huang CQ, et al. Design of 2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropy-laminopyrazolo[1,5-a]pyrimidine (NBI 30775/R121919) and structure: activity relationships of a series of potent and orally active corticotropin-releasing factor receptor antagonists. J Med Chem 2004 Sep 9; 47(19): 4787–98

    Article  PubMed  CAS  Google Scholar 

  86. Chen C, Dagnino R Jr, De Souza EB, et al. Design and synthesis of a series of non-peptide high-affinity human corticotropin-releasing factor1 receptor antagonists. J Med Chem 1996 Oct 25; 39(22): 4358–60

    Article  PubMed  CAS  Google Scholar 

  87. Jagoda E, Contoreggi C, Lee MJ, et al. Autoradiographic visualization of corticotropin releasing hormone type 1 receptors with a nonpeptide ligand: synthesis of [(76)Br]MJL-1-109-2. J Med Chem 2003 Aug 14; 46(17): 3559–62

    Article  PubMed  CAS  Google Scholar 

  88. McCarthy JR, Heinrichs SC, Grigoriadis DE. Recent advances with the CRF1 receptor: design of small molecule inhibitors, receptor subtypes and clinical indications. Curr Pharm Des 1999 May; 5(5): 289–315

    PubMed  CAS  Google Scholar 

  89. Okuyama S, Chaki S, Kawashima N, et al. Receptor binding, behavioral, and electrophysiological profiles of nonpeptide corticotropin-releasing factor subtype 1 receptor antagonists CRA1000 and CRA1001. J Pharmacol Exp Ther 1999 May; 289(2): 926–35

    PubMed  CAS  Google Scholar 

  90. Zorrilla EP, Koob GF. The therapeutic potential of CRF1 antagonists for anxiety. Expert Opin Investig Drugs 2004 Jul; 13(7): 799–828

    Article  PubMed  CAS  Google Scholar 

  91. Gehlert DR, Cippitelli A, Thorsell A, et al. 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 Mar 7; 27(10): 2718–26

    Article  PubMed  CAS  Google Scholar 

  92. Richardson HN, Zhao Y, Fekete EM, et al. MPZP: a novel small molecule corticotropin-releasing factor type 1 receptor (CRF1) antagonist. Pharmacol Biochem Behav 2008 Feb; 88(4): 497–510

    Article  PubMed  CAS  Google Scholar 

  93. Zorrilla EP, Koob GF. Progress in corticotropin-releasing factor-1 antagonist development. Drug Discov Today 2010 May; 15(9–10): 371–83

    Article  PubMed  CAS  Google Scholar 

  94. Specio SE, Wee S, O’Dell LE, et al. CRF(1) receptor antagonists attenuate escalated cocaine self-administration in rats. Psychopharmacology (Berl) 2008 Feb; 196(3): 473–82

    Article  CAS  Google Scholar 

  95. Goeders NE, Guerin GF. Effects of the CRH receptor antagonist CP-154,526 on intravenous cocaine self-administration in rats. Neuropsychopharmacology 2000 Nov; 23(5): 577–86

    Article  PubMed  CAS  Google Scholar 

  96. Mello NK, Negus SS, Rice KC, et al. Effects of the CRF1 antagonist antalarmin on cocaine self-administration and discrimination in rhesus monkeys. Pharmacol Biochem Behav 2006 Dec; 85(4): 744–51

    Article  PubMed  CAS  Google Scholar 

  97. Basso AM, Spina M, Rivier J, et al. Corticotropin-releasing factor antagonist attenuates the ‘anxiogenic-like’ effect in the defensive burying paradigm but not in the elevated plus-maze following chronic cocaine in rats. Psychopharmacology (Berl) 1999 Jul; 145(1): 21–30

    Article  CAS  Google Scholar 

  98. Erb S, Shaham Y, Stewart J. The role of corticotropinreleasing factor and corticosterone in stress- and cocaine-induced relapse to cocaine seeking in rats. J Neurosci 1998 Jul 15; 18(14): 5529–36

    PubMed  CAS  Google Scholar 

  99. Shaham Y, Erb S, Leung S, et al. CP-154,526, a selective, non-peptide antagonist of the corticotropin-releasing factor1 receptor attenuates stress-induced relapse to drug seeking in cocaine- and heroin-trained rats. Psychopharmacology (Berl) 1998 May; 137(2): 184–90

    Article  CAS  Google Scholar 

  100. Goeders NE, Clampitt DM. Potential role for the hypothalamo-pituitary-adrenal axis in the conditioned reinforcer-induced reinstatement of extinguished cocaine seeking in rats. Psychopharmacology (Berl) 2002 May; 161(3): 222–32

    Article  CAS  Google Scholar 

  101. Skelton KH, Oren D, Gutman DA, et al. The CRF1 receptor antagonist, R121919, attenuates the severity of precipitated morphine withdrawal. Eur J Pharmacol 2007 Sep 24; 571(1): 17–24

    Article  PubMed  CAS  Google Scholar 

  102. Greenwell TN, Funk CK, Cottone P, et al. Corticotropin-releasing factor-1 receptor antagonists decrease heroin self-administration in long-but not short-access rats. Addict Biol 2009 Apr; 14(2): 130–43

    Article  PubMed  CAS  Google Scholar 

  103. Negus SS, Rice KC. Mechanisms of withdrawal-associated increases in heroin self-administration: pharmacologic modulation of heroin vs food choice in heroin-dependent rhesus monkeys. Neuropsychopharmacology 2009 Mar; 34(4): 899–911

    Article  PubMed  CAS  Google Scholar 

  104. Heinrichs SC, Menzaghi F, Schulteis G, et al. Suppression of corticotropin-releasing factor in the amygdala attenuates aversive consequences of morphine withdrawal. Behav Pharmacol 1995 Jan; 6(1): 74–80

    Article  PubMed  CAS  Google Scholar 

  105. Stinus L, Cador M, Zorrilla EP, et al. Buprenorphine and a CRF1 antagonist block the acquisition of opiate withdrawal-induced conditioned place aversion in rats. Neuropsychopharmacology 2005 Jan; 30(1): 90–8

    Article  PubMed  CAS  Google Scholar 

  106. Shaham Y, Funk D, Erb S, et al. Corticotropin-releasing factor, but not corticosterone, is involved in stress-induced relapse to heroin-seeking in rats. J Neurosci 1997 Apr 1; 17(7): 2605–14

    PubMed  CAS  Google Scholar 

  107. Wang J, Fang Q, Liu Z, et al. Region-specific effects of brain corticotropin-releasing factor receptor type 1 blockade on footshock-stress- or drug-priming-induced reinstatement of morphine conditioned place preference in rats. Psychopharmacology (Berl) 2006 Mar; 185(1): 19–28

    Article  CAS  Google Scholar 

  108. Rivier C, Rivier J, Lee S. Importance of pituitary and brain receptors for corticotrophin-releasing factor in modulating alcohol-induced ACTH secretion in the rat. Brain Res 1996 May 20; 721(1–2): 83–90

    Article  PubMed  CAS  Google Scholar 

  109. Funk CK, Zorrilla EP, Lee MJ, et al. Corticotropin-releasing factor 1 antagonists selectively reduce ethanol self-administration in ethanol-dependent rats. Biol Psychiatry 2007 Jan 1; 61(1): 78–86

    Article  PubMed  CAS  Google Scholar 

  110. Marinelli PW, Funk D, Juzytsch W, et al. The CRF1 receptor antagonist antalarmin attenuates yohimbine-induced increases in operant alcohol self-administration and reinstatement of alcohol seeking in rats. Psychopharmacology (Berl) 2007 Dec; 195(3): 345–55

    Article  CAS  Google Scholar 

  111. Sparta DR, Sparrow AM, Lowery EG, et al. 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 Feb; 32(2): 259–65

    Article  PubMed  CAS  Google Scholar 

  112. Lowery EG, Sparrow AM, Breese GR, et al. The CRF-1 receptor antagonist, CP-154,526, attenuates stress-induced increases in ethanol consumption by BALB/cJ mice. Alcohol Clin Exp Res 2008 Feb; 32(2): 240–8

    Article  PubMed  CAS  Google Scholar 

  113. Lowery EG, Spanos M, Navarro M, et al. CRF-1 antagonist and CRF-2 agonist decrease binge-like ethanol drinking in C57BL/6J mice independent of the HPA axis. Neuropsychopharmacology 2010 May; 35(6): 1241–52

    Article  PubMed  CAS  Google Scholar 

  114. Sabino V, Cottone P, Koob GF, et al. Dissociation between opioid and CRF1 antagonist sensitive drinking in Sardinian alcohol-preferring rats. Psychopharmacology (Berl) 2006 Dec; 189(2): 175–86

    Article  CAS  Google Scholar 

  115. Gilpin NW, Richardson HN, Koob GF. 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 Sep; 32(9): 1535–42

    Article  PubMed  CAS  Google Scholar 

  116. Valdez GR, Roberts AJ, Chan K, et al. 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 Oct; 26(10): 1494–501

    Article  PubMed  CAS  Google Scholar 

  117. Baldwin HA, Rassnick S, Rivier J, et al. CRF antagonist reverses the ‘anxiogenic’ response to ethanol withdrawal in the rat. Psychopharmacology (Berl) 1991; 103(2): 227–32

    Article  CAS  Google Scholar 

  118. Wills TA, Knapp DJ, Overstreet DH, et al. Sensitization, duration, and pharmacological blockade of anxiety-like behavior following repeated ethanol withdrawal in adolescent and adult rats. Alcohol Clin Exp Res 2009 Mar; 33(3): 455–63

    Article  PubMed  Google Scholar 

  119. 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 Sep 15; 22(18): 7856–61

    PubMed  CAS  Google Scholar 

  120. Le AD, Harding S, Juzytsch W, et al. The role of corticotrophin-releasing factor in stress-induced relapse to alcohol-seeking behavior in rats. Psychopharmacology (Berl) 2000 Jun; 150(3): 317–24

    Article  CAS  Google Scholar 

  121. Sparta DR, Ferraro 3rd FM, Fee JR, et al. 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 Jan; 33(1): 31–42

    Article  PubMed  CAS  Google Scholar 

  122. Okada S, Shimizu T, Yokotani K. Extrahypothalamic corticotropin-releasing hormone mediates (−)-nicotine-induced elevation of plasma corticosterone in rats. Eur J Pharmacol 2003 Jul 25; 473(2–3): 217–23

    Article  PubMed  CAS  Google Scholar 

  123. Tucci S, Cheeta S, Seth P, et al. Corticotropin releasing factor antagonist, alpha-helical CRF(9–41), reverses nicotine-induced conditioned, but not unconditioned, anxiety. Psychopharmacology (Berl) 2003 May; 167(3): 251–6

    CAS  Google Scholar 

  124. Marcinkiewcz CA, Prado MM, Isaac SK, et al. Corticotropin-releasing factor within the central nucleus of the amygdala and the nucleus accumbens shell mediates the negative affective state of nicotine withdrawal in rats. Neuropsychopharmacology 2009 Jun; 34(7): 1743–52

    Article  PubMed  CAS  Google Scholar 

  125. Zislis G, Desai TV, Prado M, et al. Effects of the CRF receptor antagonist D-Phe CRF(12–41) and the alpha2-adrenergic receptor agonist clonidine on stress-induced reinstatement of nicotine-seeking behavior in rats. Neuropharmacology 2007 Dec; 53(8): 958–66

    Article  PubMed  CAS  Google Scholar 

  126. Bruijnzeel AW, Prado M, Isaac S. Corticotropin-releasing factor-1 receptor activation mediates nicotine withdrawal-induced deficit in brain reward function and stress-induced relapse. Biol Psychiatry 2009 Jul 15; 66(2): 110–7

    Article  PubMed  CAS  Google Scholar 

  127. Rodriguez de Fonseca F, Rubio P, Menzaghi F, et al. Corticotropin-releasing factor (CRF) antagonist [D-Phe12,Nle21,38,C alpha MeLeu37]CRF attenuates the acute actions of the highly potent cannabinoid receptor agonist HU-210 on defensive-withdrawal behavior in rats. J Pharmacol Exp Ther 1996 Jan; 276(1): 56–64

    PubMed  CAS  Google Scholar 

  128. Cottone P, Sabino V, Roberto M, et al. CRF system recruitment mediates dark side of compulsive eating. Proc Natl Acad Sci U S A 2009 Nov 24; 106(47): 20016–20

    PubMed  CAS  Google Scholar 

  129. Ghitza UE, Gray SM, Epstein DH, et al. The anxiogenic drug yohimbine reinstates palatable food seeking in a rat relapse model: a role of CRF1 receptors. Neuropsychopharmacology 2006 Oct; 31(10): 2188–96

    PubMed  CAS  Google Scholar 

  130. Rivier J, Rivier C, Vale W. Synthetic competitive antagonists of corticotropin-releasing factor: effect on ACTH secretion in the rat. Science 1984 May 25; 224(4651): 889–91

    Article  PubMed  CAS  Google Scholar 

  131. Menzaghi F, Howard RL, Heinrichs SC, et al. Characterization of a novel and potent corticotropin-releasing factor antagonist in rats. J Pharmacol Exp Ther 1994 May; 269(2): 564–72

    PubMed  CAS  Google Scholar 

  132. Erb S, Stewart J. A role for the bed nucleus of the stria terminalis, but not the amygdala, in the effects of corticotropin-releasing factor on stress-induced reinstatement of cocaine seeking. J Neurosci 1999 Oct 15; 19(20): RC35

    PubMed  CAS  Google Scholar 

  133. Wang B, Shaham Y, Zitzman D, et al. Cocaine experience establishes control of midbrain glutamate and dopamine by corticotropin-releasing factor: a role in stress-induced relapse to drug seeking. J Neurosci 2005 Jun 1; 25(22): 5389–96

    Article  PubMed  CAS  Google Scholar 

  134. Shalev U, Finnie PS, Quinn T, et al. A role for corticotropin-releasing factor, but not corticosterone, in acute food-deprivation-induced reinstatement of heroin seeking in rats. Psychopharmacology (Berl) 2006 Aug; 187(3): 376–84

    Article  CAS  Google Scholar 

  135. Finn DA, Snelling C, Fretwell AM, et al. 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 Jun; 31(6): 939–49

    Article  PubMed  CAS  Google Scholar 

  136. Rassnick S, Heinrichs SC, Britton KT, et al. Microinjection of a corticotropin-releasing factor antagonist into the central nucleus of the amygdala reverses anxiogenic-like effects of ethanol withdrawal. Brain Res 1993 Mar 5; 605(1): 25–32

    Article  PubMed  CAS  Google Scholar 

  137. Bruijnzeel AW, Zislis G, Wilson C, et al. Antagonism of CRF receptors prevents the deficit in brain reward function associated with precipitated nicotine withdrawal in rats. Neuropsychopharmacology 2007 Apr; 32(4): 955–63

    Article  PubMed  CAS  Google Scholar 

  138. Bruijnzeel AW, Small E, Pasek TM, et al. Corticotropin-releasing factor mediates the dysphoria-like state associated with alcohol withdrawal in rats. Behav Brain Res 2010 Jul 11; 210(2): 288–91

    Article  PubMed  CAS  Google Scholar 

  139. Schulz DW, Mansbach RS, Sprouse J, et al. CP-154,526: a potent and selective nonpeptide antagonist of corticotropin releasing factor receptors. Proc Natl Acad Sci U S A 1996 Sep 17; 93(19): 10477–82

    Article  PubMed  CAS  Google Scholar 

  140. Zorrilla EP, Valdez GR, Nozulak J, et al. Effects of antalarmin, a CRF type 1 receptor antagonist, on anxiety-like behavior and motor activation in the rat. Brain Res 2002 Oct 18; 952(2): 188–99

    Article  PubMed  CAS  Google Scholar 

  141. Moffett MC, Goeders NE. CP-154,526, a CRF type-1 receptor antagonist, attenuates the cue-and methamphetamine-induced reinstatement of extinguished methamphetamine-seeking behavior in rats. Psychopharmacology (Berl) 2007 Feb; 190(2): 171–80

    Article  PubMed  CAS  Google Scholar 

  142. Lu L, Ceng X, Huang M. Corticotropin-releasing factor receptor type I mediates stress-induced relapse to opiate dependence in rats. Neuroreport 2000 Aug 3; 11(11): 2373–8

    Article  PubMed  CAS  Google Scholar 

  143. Lu L, Liu D, Ceng X, et al. Differential roles of corticotropin-releasing factor receptor subtypes 1 and 2 in opiate withdrawal and in relapse to opiate dependence. Eur J Neurosci 2000 Dec; 12(12): 4398–404

    PubMed  CAS  Google Scholar 

  144. Lu L, Liu D, Ceng X. Corticotropin-releasing factor receptor type 1 mediates stress-induced relapse to cocaine-conditioned place preference in rats. Eur J Pharmacol 2001 Mar; 415(2–3): 203–8

    Article  PubMed  CAS  Google Scholar 

  145. Breese GR, Overstreet DH, Knapp DJ, et al. 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 Sep; 30(9): 1662–9

    Article  PubMed  CAS  Google Scholar 

  146. Wills TA, Knapp DJ, Overstreet DH, et al. Interactions of stress and CRF in ethanol-withdrawal induced anxiety in adolescent and adult rats. Alcohol Clin Exp Res 2010 Sep 1; 34(9): 1603–12

    Article  PubMed  Google Scholar 

  147. Arborelius L, Skelton KH, Thrivikraman KV, et al. Chronic administration of the selective corticotropin-releasing factor 1 receptor antagonist CP-154,526: behavioral, endocrine and neurochemical effects in the rat. J Pharmacol Exp Ther 2000 Aug; 294(2): 588–97

    PubMed  CAS  Google Scholar 

  148. Overstreet DH, Knapp DJ, Breese GR. Modulation of multiple ethanol withdrawal-induced anxiety-like behavior by CRF and CRF1 receptors. Pharmacol Biochem Behav 2004 Feb; 77(2): 405–13

    Article  PubMed  CAS  Google Scholar 

  149. Knapp DJ, Overstreet DH, Moy SS, et al. SB242084, flumazenil, and CRA1000 block ethanol withdrawal-induced anxiety in rats. Alcohol 2004 Feb; 32(2): 101–11

    Article  PubMed  CAS  Google Scholar 

  150. Heinrichs SC, De Souza EB, Schulteis G, et al. Brain penetrance, receptor occupancy and antistress in vivo efficacy of a small molecule corticotropin releasing factor type I receptor selective antagonist. Neuropsychopharmacology 2002 Aug; 27(2): 194–202

    Article  PubMed  CAS  Google Scholar 

  151. Keck ME, Welt T, Wigger A, et al. The anxiolytic effect of the CRH(1) receptor antagonist R121919 depends on innate emotionality in rats. Eur J Neurosci 2001 Jan; 13(2): 373–80

    Article  PubMed  CAS  Google Scholar 

  152. Oshima A, Flachskamm C, Reul JM, et al. Altered serotonergic neurotransmission but normal hypothalamic-pituitary-adrenocortical axis activity in mice chronically treated with the corticotropin-releasing hormone receptor type 1 antagonist NBI 30775. Neuropsychopharmacology 2003 Dec; 28(12): 2148–59

    PubMed  CAS  Google Scholar 

  153. Kunzel HE, Zobel AW, Nickel T, et al. Treatment of depression with the CRH-1-receptor antagonist R121919: endocrine changes and side effects. J Psychiatr Res 2003 Nov–Dec; 37(6): 525–33

    Article  PubMed  Google Scholar 

  154. Zobel AW, Nickel T, Kunzel HE, et al. Effects of the high-affinity corticotropin-releasing hormone receptor 1 antagonist R121919 in major depression: the first 20 patients treated. J Psychiatr Res 2000 May–Jun; 34(3): 171–81

    Article  PubMed  CAS  Google Scholar 

  155. Funk CK, Koob GF. A CRF(2) agonist administered into the central nucleus of the amygdala decreases ethanol self-administration in ethanol-dependent rats. Brain Res 2007 Jun 25; 1155: 172–8

    Article  PubMed  CAS  Google Scholar 

  156. Valdez GR, Sabino V, Koob GF. Increased anxiety-like behavior and ethanol self-administration in dependent rats: reversal via corticotropin-releasing factor-2 receptor activation. Alcohol Clin Exp Res 2004 Jun; 28(6): 865–72

    Article  PubMed  CAS  Google Scholar 

  157. Sharpe AL, Phillips TJ. Central urocortin 3 administration decreases limited-access ethanol intake in nondependent mice. Behav Pharmacol 2009 Jul; 20(4): 346–51

    Article  PubMed  CAS  Google Scholar 

  158. Wang B, You ZB, Rice KC, et al. Stress-induced relapse to cocaine seeking: roles for the CRF(2) receptor and CRF-binding protein in the ventral tegmental area of the rat. Psychopharmacology (Berl) 2007 Aug; 193(2): 283–94

    Article  CAS  Google Scholar 

  159. Vuong SM, Oliver HA, Scholl JL, et al. Increased anxiety-like behavior of rats during amphetamine withdrawal is reversed by CRF2 receptor antagonism. Behav Brain Res 2010 Mar 17; 208(1): 278–81

    Article  PubMed  CAS  Google Scholar 

  160. Ruhmann A, Bonk I, Lin CR, et al. Structural requirements for peptidic antagonists of the corticotropin-releasing factor receptor (CRFR): development of CRFR2beta-selective antisauvagine-30. Proc Natl Acad Sci U S A 1998 Dec 22; 95(26): 15264–9

    Article  PubMed  CAS  Google Scholar 

  161. Bruijnzeel AW, Gold MS. The role of corticotropin-releasing factor-like peptides in cannabis, nicotine, and alcohol dependence. Brain Res Brain Res Rev 2005 Nov; 49(3): 505–28

    Article  PubMed  CAS  Google Scholar 

  162. Heilig M, Egli M, Crabbe JC, et al. Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked? Addict Biol 2010 Apr; 15(2): 169–84

    Article  PubMed  Google Scholar 

  163. Bossert JM, Ghitza UE, Lu L, et al. Neurobiology of relapse to heroin and cocaine seeking: an update and clinical implications. Eur J Pharmacol 2005 Dec 5; 526(1–3): 36–50

    Article  PubMed  CAS  Google Scholar 

  164. Rylkova D, Shah HP, Small E, et al. Deficit in brain reward function and acute and protracted anxiety-like behavior after discontinuation of a chronic alcohol liquid diet in rats. Psychopharmacology (Berl) 2009 Apr; 203(3): 629–40

    Article  CAS  Google Scholar 

  165. Zhao Y, Weiss F, Zorrilla EP. Remission and resurgence of anxiety-like behavior across protracted withdrawal stages in ethanol-dependent rats. Alcohol Clin Exp Res 2007 Sep; 31(9): 1505–15

    Article  PubMed  Google Scholar 

  166. Valdez GR, Zorrilla EP, Roberts AJ, et al. Antagonism of corticotropin-releasing factor attenuates the enhanced responsiveness to stress observed during protracted ethanol abstinence. Alcohol 2003 Feb; 29(2): 55–60

    Article  PubMed  CAS  Google Scholar 

  167. Kauer JA, Malenka RC. Synaptic plasticity and addiction. Nat Rev Neurosci 2007 Nov; 8(11): 844–58

    Article  PubMed  CAS  Google Scholar 

  168. Fu Y, Pollandt S, Liu J, et al. Long-term potentiation (LTP) in the central amygdala (CeA) is enhanced after prolonged withdrawal from chronic cocaine and requires CRF1 receptors. J Neurophysiol 2007 Jan; 97(1): 937–41

    Article  PubMed  CAS  Google Scholar 

  169. Nie Z, Schweitzer P, Roberts AJ, et al. Ethanol augments GABAergic transmission in the central amygdala via CRF1 receptors. Science 2004 Mar 5; 303(5663): 1512–4

    Article  PubMed  CAS  Google Scholar 

  170. Roberto M, Cruz MT, Gilpin NW, et al. Corticotropin releasing factor-induced amygdala gamma-aminobutyric acid release plays a key role in alcohol dependence. Biol Psychiatry 2010 May 1; 67(9): 831–9

    Article  PubMed  CAS  Google Scholar 

  171. Pollandt S, Liu J, Orozco-Cabal L, et al. Cocaine withdrawal enhances long-term potentiation induced by corticotropin-releasing factor at central amygdala glutamatergic synapses via CRF, NMDA receptors and PKA. Eur J Neurosci 2006 Sep; 24(6): 1733–43

    Article  PubMed  Google Scholar 

  172. Krishnan B, Centeno M, Pollandt S, et al. Dopamine receptor mechanisms mediate corticotropinreleasing factor-induced long-term potentiation in the rat amygdala following cocaine withdrawal. Eur J Neurosci 2010; 31: 1027–42

    Article  PubMed  Google Scholar 

  173. Kash TL, Winder DG. Neuropeptide Y and corticotropin-releasing factor bi-directionally modulate inhibitory synaptic transmission in the bed nucleus of the stria terminalis. Neuropharmacology 2006 Oct; 51(5): 1013–22

    Article  PubMed  CAS  Google Scholar 

  174. Francesconi W, Berton F, Repunte-Canonigo V, et al. 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 Apr 29; 29(17): 5389–401

    Article  PubMed  CAS  Google Scholar 

  175. Hahn J, Hopf FW, Bonci A. Chronic cocaine enhances corticotropin-releasing factor-dependent potentiation of excitatory transmission in ventral tegmental area dopamine neurons. J Neurosci 2009 May 20; 29(20): 6535–44

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank Michael Arends for editorial assistance in the preparation of this manuscript and Janet Hightower for help with figure preparation. Financial support was received from the Pearson Center for Alcoholism and Addiction Research and National Institutes of Health grant DK26741 from the National Institute of Diabetes and Digestive and Kidney Diseases, AA06420, AA08459 and AA018914 from the National Institute on Alcohol Abuse and Alcoholism, and DA04043, DA04398 and DA023957 from the National Institute on Drug Abuse. G.F. Koob and E.P. Zorrilla are inventors on a provisional patent filed for CRF1 antagonists (US provisional patent number 60/902,479). M.L. Logrip has no conflicts of interest to disclose. This is publication number 20696 from The Scripps Research Institute.

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  1. Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA, 92037, USA

    Marian L. Logrip PhD, George F. Koob & Eric P. Zorrilla

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Logrip, M.L., Koob, G.F. & Zorrilla, E.P. Role of Corticotropin-Releasing Factor in Drug Addiction. CNS Drugs 25, 271–287 (2011). https://doi.org/10.2165/11587790-000000000-00000

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