Naltrexone selectively elevates GABAergic neuroactive steroid levels in heavy drinkers with the ASP40 allele of the OPRM1 gene: A pilot investigation

Alcoholism: Clinical and Experimental Research

Volumn 34, Issue 8, 2010, Pages 1479-1487

  Ray, Lara A ^a   Hutchison, Kent E ^b   Ashenhurst, James R ^a   Morrow, A Leslie ^c  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF NEW MEXICO   (United States)

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

Author keywords

Alcohol; Genetics; Naltrexone; Neuroactive Steroid; OPRM1

Indexed keywords

3ALPHA HYDROXY 5ALPHA PREGNAN 20 ONE; ALCOHOL; NALTREXONE; OPRM1 PROTEIN; PLACEBO; PROTEIN; RIBOFLAVIN; UNCLASSIFIED DRUG;

ADULT; ALCOHOL CONSUMPTION; ALLELE; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRINKING BEHAVIOR; FEMALE; GABAERGIC SYSTEM; GENE MUTATION; GENETIC POLYMORPHISM; GENOTYPE; HUMAN; PILOT STUDY; PRIORITY JOURNAL; RADIOIMMUNOASSAY; RANDOMIZED CONTROLLED TRIAL; SINGLE NUCLEOTIDE POLYMORPHISM; STEROID BLOOD LEVEL;

EID: 77954890033     PISSN: 01456008     EISSN: 15300277     Source Type: Journal    
DOI: 10.1111/j.1530-0277.2010.01233.x     Document Type: Article

References (70)

1. Adinoff B, Iranmanesh A, Veldhuis J, Fisher L (1998) Disturbances of the stress response: the role of the HPA axis during alcohol withdrawal and abstinence. Alcohol Health Res World 22 : 67 72.
2. Adinoff B, Junghanns K, Kiefer F, Krishnan-Sarin S (2005) Suppression of the HPA axis stress-response: implications for relapse. Alcohol Clin Exp Res 29 : 1351 1355.
3. Allen JP, Litten RZ, Fertig JB, Babor T (1997) A review of research on the Alcohol Use Disorders Identification Test (AUDIT). Alcohol Clin Exp Res 21 : 613 619.
4. Anton RF, Drobes DJ, Voronin K, Durazo-Avizu R, Moak D (2004) Naltrexone effects on alcohol consumption in a clinical laboratory paradigm: temporal effects of drinking. Psychopharmacology (Berl) 173 : 32 40.
5. Anton RF, Moak DH, Waid LR, Latham PK, Malcolm RJ, Dias JK (1999) Naltrexone and cognitive behavioral therapy for the treatment of outpatient alcoholics: results of a placebo-controlled trial. Am J Psychiatry 156 : 1758 1764.
6. Anton RF, O'Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, Gastfriend DR, Hosking JD, Johnson BA, LoCastro JS, Longabaugh R, Mason BJ, Mattson ME, Miller WR, Pettinati HM, Randall CL, Swift R, Weiss RD, Williams LD, Zweben A (2006) Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA 295 : 2003 2017.
7. Anton RF, Oroszi G, O'Malley S, Couper D, Swift R, Pettinati H, Goldman D (2008) An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study. Arch Gen Psychiatry 65 : 135 144.
8. Barbaccia ML, Affricano D, Trabucchi M, Purdy RH, Colombo G, Agabio R, Gessa GL (1999) Ethanol markedly increases "GABAergic" neurosteroids in alcohol-preferring rats. Eur J Pharmacol 384 : R1 R2.
9. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21 : 263 265.
10. Boyd KN, Kumar S, O'Buckley TK, Porcu P, Morrow AL (2010) Ethanol induction of steroidogenesis in rat adrenal and brain is dependent upon pituitary ACTH release and de novo adrenal StAR synthesis. J Neurochem 112 : 784 796.
11. Del Boca FK, Kranzler HR, Brown J, Korner PF (1996) Assessment of medication compliance in alcoholics through UV light detection of a riboflavin tracer. Alcohol Clin Exp Res 20 : 1412 1417.
12. Drobes DJ, Anton RF, Thomas SE, Voronin K (2004) Effects of naltrexone and nalmefene on subjective response to alcohol among non-treatment-seeking alcoholics and social drinkers. Alcohol Clin Exp Res 28 : 1362 1370.
13. Farren CK, O'Malley S, Grebski G, Maniar S, Porter M, Kreek MJ (1999) Variable dose naltrexone-induced hypothalamic-pituitary-adrenal stimulation in abstinent alcoholics: a preliminary study. Alcohol Clin Exp Res 23 : 502 508.
14. Freeman B, Powell J, Ball D, Hill L, Craig I, Plomin R (1997) DNA by mail: an inexpensive and noninvasive method for collecting DNA samples from widely dispersed populations. Behav Genet 27 : 251 257.
15. Gelernter J, Gueorguieva R, Kranzler HR, Zhang H, Cramer J, Rosenheck R, Krystal JH (2007) Opioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence: results from the VA Cooperative Study. Alcohol Clin Exp Res 31 : 555 563.
16. Genazzani AR, Petraglia F, Bernardi F, Casarosa E, Salvestroni C, Tonetti A, Nappi RE, Luisi S, Palumbo M, Purdy RH, Luisi M (1998) Circulating levels of allopregnanolone in humans: gender, age, and endocrine influences. J Clin Endocrinol Metab 83 : 2099 2103.
17. Girdler SS, Straneva PA, Light KC, Pedersen CA, Morrow AL (2001) Allopregnanolone levels and reactivity to mental stress in premenstrual dysphoric disorder. Biol Psychiatry 49 : 788 797.
18. Hernandez-Avila CA, Covault J, Wand G, Zhang H, Gelernter J, Kranzler HR (2007) Population-specific effects of the Asn40Asp polymorphism at the mu-opioid receptor gene (OPRM1) on HPA-axis activation. Pharmacogenet Genomics 17 : 1031 1038.
19. Hernandez-Avila CA, Oncken C, Van KirkJ, Wand G, Kranzler HR (2002) Adrenocorticotropin and cortisol responses to a naloxone challenge and risk of alcoholism. Biol Psychiatry 51 : 652 658.
20. Hirani K, Khisti RT, Chopde CT (2002) Behavioral action of ethanol in Porsolt's forced swim test: modulation by 3 alpha-hydroxy-5 alpha-pregnan-20- one. Neuropharmacology 43 : 1339 1350.
21. Holdstock L, Penland SN, Morrow AL, de Wit H (2006) Moderate doses of ethanol fail to increase plasma levels of neurosteroid 3alpha-hydroxy-5alpha- pregnan-20-one-like immunoreactivity in healthy men and women. Psychopharmacology (Berl) 186 : 442 450.
22. Janis GC, Devaud LL, Mitsuyama H, Morrow AL (1998) Effects of chronic ethanol consumption and withdrawal on the neuroactive steroid 3α-hydroxy-5α-pregnan-20-one in male and female rats. Alcohol Clin Exp Res 22 : 2055 2061.
23. Johnson SW, North RA (1992) Opioids excite dopamine neurons by hyperpolarization of local interneurons. J Neurosci 12 : 483 488.
24. Junghanns K, Backhaus J, Tietz U, Lange W, Bernzen J, Wetterling T, Rink L, Driessen M (2003) Impaired serum cortisol stress response is a predictor of early relapse. Alcohol Alcohol 38 : 189 193.
25. Junghanns K, Tietz U, Dibbelt L, Kuether M, Jurth R, Ehrenthal D, Blank S, Backhaus J (2005) Attenuated salivary cortisol secretion under cue exposure is associated with early relapse. Alcohol Alcohol 40 : 80 85.
26. Kemper A, Koalick F, Thiele H, Retzow A, Rathsack R, Nickel B (1990) Cortisol and beta-endorphin response in alcoholics and alcohol abusers following a high naloxone dosage. Drug Alcohol Depend 25 : 319 326.
27. Khisti RT, VanDoren MJ, O'Buckley T, Morrow AL (2003) Neuroactive steroid 3 alpha-hydroxy-5 alpha-pregnan-20-one modulates ethanol-induced loss of righting reflex in rats. Brain Res 980 : 255 265.
28. Kiefer F, Jahn H, Otte C, Naber D, Wiedemann K (2006) Hypothalamic-pituitary-adrenocortical axis activity: a target of pharmacological anticraving treatment? Biol Psychiatry 60 : 74 76.
29. King AC, Schluger J, Gunduz M, Borg L, Perret G, Ho A, Kreek MJ (2002) Hypothalamic-pituitary-adrenocortical (HPA) axis response and biotransformation of oral naltrexone: preliminary examination of relationship to family history of alcoholism. Neuropsychopharmacology 26 : 778 788.
30. Lench N, Stanier P, Williamson R (1988) Simple non-invasive method to obtain DNA for gene analysis. Lancet 1 : 1356 1358.
31. Li TK, Yin SJ, Crabb DW, O'Connor S, Ramchandani VA (2001) Genetic and environmental influences on alcohol metabolism in humans. Alcohol Clin Exp Res 25 : 136 144.
32. Livak KJ (1999) Allelic discrimination using fluorogenic probes and the 5' nuclease assay. Genet Anal 14 : 143 149.
33. Matthews DB, Morrow AL, Tokunaga S, McDaniel JR (2002) Acute ethanol administration and acute allopregnanolone administration impair spatial memory in the Morris water task. Alcohol Clin Exp Res 26 : 1747 1751.
34. McCaul ME, Wand GS, Stauffer R, Lee SM, Rohde CA (2001) Naltrexone dampens ethanol-induced cardiovascular and hypothalamic- pituitary-adrenal axis activation. Neuropsychopharmacology 25 : 537 547.
35. Monti PM, Rohsenow DJ, Swift RM, Gulliver SB, Colby SM, Mueller TI, Brown RA, Gordon A, Abrams DB, Niaura RS, Asher MK (2001) Naltrexone and cue exposure with coping and communication skills training for alcoholics: treatment process and 1-year outcomes. Alcohol Clin Exp Res 25 : 1634 1647.
36. Morrow AL (2007) Recent developments in the significance and therapeutic relevance of neuroactive steroids - Introduction to the special issue. Pharmacol Ther 116 : 1 6.
37. Morrow AL, Janis GC, VanDoren MJ, Matthews DB, Samson HH, Janak PH, Grant KA (1999) Neurosteroids mediate pharmacological effects of ethanol: a new mechanism of ethanol action? Alcohol Clin Exp Res 23 : 1933 1940.
38. Morrow AL, Pace JR, Purdy RH, Paul SM (1990) Characterization of steroid interactions with γ-aminobutyric acid receptor-gated chloride ion channels: evidence for multiple steroid recognition sites. Mol Pharmacol 37 : 263 270.
39. Morrow AL, VanDoren MJ, Devaud LL (1998) Effects of progesterone or neuroactive steroid? Nature 395 : 652 653.
40. Morrow AL, VanDoren MJ, Penland SN, Matthews DB (2001) The role of GABAergic neuroactive steroids in ethanol action, tolerance and dependence. Brain Res Brain Res Rev 37 : 98 109.
41. Naber D, Pickar D, Davis GC, Cohen RM, Jimerson DC, Elchisak MA, Defraites EG, Kalin NH, Risch SC, Buchsbaum MS (1981) Naloxone effects on beta-endorphin, cortisol, prolactin, growth hormone, HVA and MHPG in plasma of normal volunteers. Psychopharmacology (Berl) 74 : 125 128.
42. Naert G, Maurice T, Tapia-Arancibia L, Givalois L (2007) Neuroactive steroids modulate HPA axis activity and cerebral brain-derived neurotrophic factor (BDNF) protein levels in adult male rats. Psychoneuroendocrinology 32 : 1062 1078.
43. Nyberg S, Andersson A, Zingmark E, Wahlstrom G, Backstrom T, Sundstrom-Poromaa I (2005) The effect of a low dose of alcohol on allopregnanolone serum concentrations across the menstrual cycle in women with severe premenstrual syndrome and controls. Psychoneuroendocrinology 30 : 892 901.
44. O'Connor S, Morzorati S, Christian J, Li TK (1998) Clamping breath alcohol concentration reduces experimental variance: application to the study of acute tolerance to alcohol and alcohol elimination rate. Alcohol Clin Exp Res 22 : 202 210.
45. O'Dell LE, Roberts AJ, Smith RT, Koob GF (2004) Enhanced alcohol self-administration after intermittent versus continuous alcohol vapor exposure. Alcohol Clin Exp Res 28 : 1676 1682.
46. Olive MF, Mehmert KK, Koenig HN, Camarini R, Kim JA, Nannini MA, Ou CJ, Hodge CW (2003) A role for corticotropin releasing factor (CRF) in ethanol consumption, sensitivity, and reward as revealed by CRF-deficient mice. Psychopharmacology (Berl) 165 : 181 187.
47. O'Malley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B (1992) Naltrexone and coping skills therapy for alcohol dependence. A controlled study. Arch Gen Psychiatry 49 : 881 887.
48. O'Malley SS, Krishnan-Sarin S, Farren C, Sinha R, Kreek MJ (2002) Naltrexone decreases craving and alcohol self-administration in alcohol-dependent subjects and activates the hypothalamo-pituitary- adrenocortical axis. Psychopharmacology (Berl) 160 : 19 29.
49. Oslin DW, Berrettini W, Kranzler HR, Pettinati H, Gelernter J, Volpicelli JR, O'Brien CP (2003) A functional polymorphism of the mu-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients. Neuropsychopharmacology 28 : 1546 1552.
50. Owens MJ, Ritchie JC, Nemeroff CB (1992) 5 alpha-pregnane-3 alpha, 21-diol-20-one (THDOC) attenuates mild stress-induced increases in plasma corticosterone via a non-glucocorticoid mechanism: comparison with alprazolam. Brain Res 573 : 353 355.
51. Patchev VK, Hassan AH, Holsboer DF, Almeida OF (1996) The neurosteroid tetrahydroprogesterone attenuates the endocrine response to stress and exerts glucocorticoid-like effects on vasopressin gene transcription in the rat hypothalamus. Neuropsychopharmacology 15 : 533 540.
52. Patchev VK, Shoaib M, Holsboer F, Almeida OF (1994) The neurosteroid tetrahydroprogesterone counteracts corticotropin-releasing hormone-induced anxiety and alters the release and gene expression of corticotropin-releasing hormone in the rat hypothalamus. Neuroscience 62 : 265 271.
53. Pierucci-Lagha A, Covault J, Feinn R, Nellissery M, Hernandez-Avila C, Oncken C, Morrow AL, Kranzler HR (2005) GABRA2 alleles moderate the subjective effects of alcohol, which are attenuated by finasteride. Neuropsychopharmacology 30 : 1193 1203.
54. Purdy RH, Morrow AL, Moore PH Jr., Paul SM (1991) Stress-induced elevations of gamma-aminobutyric acid type A receptor-active steroids in the rat brain. Proc Natl Acad Sci U S A 88 : 4553 4557.
55. Ramchandani VA, Bolane J, Li TK, O'Connor S (1999) A physiologically- based pharmacokinetic (PBPK) model for alcohol facilitates rapid BrAC clamping. Alcohol Clin Exp Res 23 : 617 623.
56. Ray LA, Hutchison KE (2004) A polymorphism of the mu-opioid receptor gene (OPRM1) and sensitivity to the effects of alcohol in humans. Alcohol Clin Exp Res 28 : 1789 1795.
57. Ray LA, Hutchison KE (2007) Effects of naltrexone on alcohol sensitivity and genetic moderators of medication response: a double-blind placebo-controlled study. Arch Gen Psychiatry 64 : 1069 1077.
58. Ray LA, Mackillop J, Leggio L, Morgan M, Hutchison KE (2009) Effects of naltrexone on cortisol levels in heavy drinkers. Pharmacol Biochem Behav 91 : 489 494.
59. Ray LA, Meskew-Stacer S, Hutchison KE (2007) The relationship between prospective self-rating of alcohol sensitivity and craving and experimental results from two alcohol challenge studies. J Stud Alcohol Drugs 68 : 379 384.
60. Ray LA, Miranda R Jr., Tidey JW, McGeary JE, MacKillop J, Gwaltney CJ, Rohsenow DJ, Swift RM, Monti PM (2010) Polymorphisms of the micro-opioid receptor and dopamine D4 receptor genes and subjective responses to alcohol in the natural environment. J Abnorm Psychol 119 : 115 125.
61. Schluger JH, Ho A, Borg L, Porter M, Maniar S, Gunduz M, Perret G, King A, Kreek MJ (1998) Nalmefene causes greater hypothalamic-pituitary-adrenal axis activation than naloxone in normal volunteers: implications for the treatment of alcoholism. Alcohol Clin Exp Res 22 : 1430 1436.
62. Schuckit MA (1994) Low level of response to alcohol as a predictor of future alcoholism. Am J Psychiatry 151 : 184 189.
63. Schuckit MA, Smith TL (1996) An 8-year follow-up of 450 sons of alcoholic and control subjects. Arch Gen Psychiatry 53 : 202 210.
64. Spitz E, Moutier R, Reed T, Busnel MC, Marchaland C, Roubertoux PL, Carlier M (1996) Comparative diagnoses of twin zygosity by SSLP variant analysis, questionnaire, and dermatoglyphic analysis. Behav Genet 26 : 55 63.
65. Swift RM, Whelihan W, Kuznetsov O, Buongiorno G, Hsuing H (1994) Naltrexone-induced alterations in human ethanol intoxication. Am J Psychiatry 151 : 1463 1467.
66. Tidey JW, Monti PM, Rohsenow DJ, Gwaltney CJ, Miranda R Jr., McGeary JE, MacKillop J, Swift RM, Abrams DB, Shiffman S, Paty JA (2008) Moderators of naltrexone's effects on drinking, urge, and alcohol effects in non-treatment-seeking heavy drinkers in the natural environment. Alcohol Clin Exp Res 32 : 58 66.
67. VanDoren MJ, Matthews DB, Janis GC, Grobin AC, Devaud LL, Morrow AL (2000) Neuroactive steroid 3 alpha-hydroxy-5 alpha-pregnan-20-one modulate electrophysiological and behavioral actions of ethanol. J Neurosci 20 : 1982 1999.
68. Volavka J, Mallya A, Bauman J, Pevnick J, Cho D, Reker D, James B, Dornbush R (1979) Hormonal and other effects of naltrexone in normal men. Adv Exp Med Biol 116 : 291 305.
69. Volpicelli JR, Alterman AI, Hayashida M, O'Brien CP (1992) Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 49 : 876 880.
70. Walker AH, Najarian D, White DL, Jaffe JF, Kanetsky PA, Rebbeck TR (1999) Collection of genomic DNA by buccal swabs for polymerase chain reaction-based biomarker assays. Environ Health Perspect 107 : 517 520.