A [11 C]Ro15 4513 PET study suggests that alcohol dependence in man is associated with reduced α5 benzodiazepine receptors in limbic regions

Journal of Psychopharmacology

Volumn 26, Issue 2, 2012, Pages 273-281

  Lingford Hughes, Anne ^a,b   Reid, Alastair G ^a,b   Myers, James ^a,b   Feeney, Adrian ^a,b   Hammers, Alexander ^b   Taylor, Lindsay G ^a,c   Rosso, Lula ^b   Turkheimer, Federico ^b   Brooks, David J ^b,d   Grasby, Paul ^b   Nutt, David J ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

^c UNIVERSITY HOSPITALS BRISTOL NHS FOUNDATION TRUST   (United Kingdom)

^d HAMMERSMITH HOSPITAL   (United Kingdom)

Author keywords

Alcoholism; benzodiazepine; memory; PET; Ro15 4513

Indexed keywords

8 AZIDO 5,6 DIHYDRO 5 METHYL 6 OXO 4H IMIDAZO[1,5 A][1,4]BENZODIAZEPINE 3 CARBOXYLIC ACID ETHYL ESTER; 8 AZIDO 5,6 DIHYDRO 5 METHYL 6 OXO 4H IMIDAZO[1,5 A][1,4]BENZODIAZEPINE 3 CARBOXYLIC ACID ETHYL ESTER C 11; ALCOHOL; ALPHA5 BENZODIAZEPINE RECEPTOR; BENZODIAZEPINE RECEPTOR; FLUMAZENIL C 11; IOMAZENIL I 123; RADIOPHARMACEUTICAL AGENT; UNCLASSIFIED DRUG; 4 AMINOBUTYRIC ACID A RECEPTOR; AZIDE; BENZODIAZEPINE DERIVATIVE; CARBON; DIAGNOSTIC AGENT;

4 AMINOBUTYRIC ACID BRAIN LEVEL; ADULT; ALCOHOL ABSTINENCE; ALCOHOLISM; AMYGDALOID NUCLEUS; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; DISEASE ASSOCIATION; DISTRIBUTION VOLUME; DRUG BINDING; DRUG BRAIN LEVEL; DRUG SYNTHESIS; DRUG UPTAKE; HIPPOCAMPUS; HUMAN; IMAGE ANALYSIS; ISOTOPE LABELING; LIMBIC CORTEX; MALE; NEUROPSYCHOLOGICAL TEST; NUCLEUS ACCUMBENS; PARAHIPPOCAMPAL GYRUS; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN LOCALIZATION; VERBAL MEMORY; CASE CONTROL STUDY; DRUG EFFECT; LIMBIC SYSTEM; MEMORY; METABOLISM; METHODOLOGY; SCINTISCANNING;

ADULT; ALCOHOLISM; AZIDES; BENZODIAZEPINES; CARBON RADIOISOTOPES; CASE-CONTROL STUDIES; ETHANOL; HUMANS; LIMBIC SYSTEM; MALE; MEMORY; NUCLEUS ACCUMBENS; POSITRON-EMISSION TOMOGRAPHY; RECEPTORS, GABA-A;

EID: 84856441700     PISSN: 02698811     EISSN: 14617285     Source Type: Journal    
DOI: 10.1177/0269881110379509     Document Type: Article

References (54)

1. Abi-Dargham A, Krystal JH, Anjilvel S, Scanley BE, Zoghbi S, Baldwin RM, et al. Alterations of benzodiazepine receptors in type II alcoholic subjects measured with SPECT and [123I]iomazenil. Am J Psychiatry. 1998 ; 155: 1550-1555 (Pubitemid 28512023)
2. Agartz I, Momenan R, Rawlings RR, Kerich MJ, Hommer DW. Hippocampal volume in patients with alcohol dependence. Arch Gen Psychiatry. 1999 ; 56: 356-363 (Pubitemid 29165182)
3. Beck AT, Ward CH, Mendelson M, Mock JE, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry. 1961 ; 4: 561-571
4. Beresford TP, Arciniegas DB, Alfers J, Clapp L, Martin B, Du Y, et al. Hippocampus volume loss due to chronic heavy drinking. Alcohol Clin Exp Res. 2006 ; 30: 1866-1870 (Pubitemid 44630088)
5. Bleich S, Sperling W, Degner D, Graesel E, Bleich K, Wilhelm J, et al. Lack of association between hippocampal volume reduction and first-onset alcohol withdrawal seizure. A volumetric MRI study. Alcohol Alcohol. 2003 ; 38: 40-44 (Pubitemid 36204363)
6. Boehm SL, Ponomarev I, Jennings AW, Whiting PJ, Rosahl TW, Garrett EM, et al. Gamma-Aminobutyric acid A receptor subunit mutant mice: new perspectives on alcohol actions. Biochem Pharmacol. 2004 ; 68: 1581-1602 (Pubitemid 39286463)
7. Brunig I, Scotti E, Sidler C, Fritschy JM. Intact sorting, targeting, and clustering of gamma-aminobutyric acid A receptor subtypes in hippocampal neurons in vitro. J Comp Neurol. 2002 ; 443: 43-55 (Pubitemid 34027568)
8. Caraiscos VB, Elliott EM, You T, Cheng VY, Belelli D, Newell JG, et al. Tonic inhibition in mouse hippocampal CA1 pyramidal neurons is mediated by alpha5 subunit-containing gamma-aminobutyric acid type A receptors. Proc Natl Acad Sci U S A. 2004 ; 101: 3662-3667 (Pubitemid 38338251)
9. A receptor alpha 1 and alpha 5 subunits in the ventral tegmental area and hippocampus. J Neurochem. 1997 ; 68: 121-127 (Pubitemid 26427299)
10. A receptors mediate the amnestic but not sedative-hypnotic effects of the general anesthetic etomidate. J Neurosci. 2006 ; 26: 3713-3720
11. A receptor. J Neurosci. 2002 ; 22: 5572-5580 (Pubitemid 35386478)
12. Crestani F, Keist R, Fritschy JM, Benke D, Vogt K, Prut L, et al. Trace fear conditioning involves hippocampal alpha5 GABA(A) receptors. Proc Natl Acad Sci U S A. 2002 ; 99: 8980-8985 (Pubitemid 34693669)
13. Cunningham VJ, Jones T. Spectral analysis of dynamic PET studies. J Cerebr Blood Flow Metab. 1993 ; 13: 15-23 (Pubitemid 23016599)
14. Davies SJC, Pandit S, Feeney A, Stephenson B, Kerwin R, Nutt DJ, et al. Is there cognitive impairment in clinically 'healthy' abstinent alcohol dependence?. Alcohol Alcohol. 2005 ; 40: 498-503 (Pubitemid 41599999)
15. A receptors enhances cognition. J Pharmacol Exp Ther. 2006 ; 316: 1335-1345 (Pubitemid 43345310)
16. Devaud LL, Smith FD, Grayson DR, Morrow AL. Chronic ethanol consumption differentially alters the expression of gamma-aminobutyric acidA receptor subunit mRNAs in rat cerebral cortex: competitive, quantitative reverse transcriptase-polymerase chain reaction analysis. Mol Pharmacol. 1995 ; 48: 861-868
17. A-receptor heterogeneity in the adult rat brain: differential regional and cellular distribution of seven major subunits. J Comp Neurol. 1995 ; 359: 154-194
18. Grobin AC, Papadeas ST, Morrow AL. Regional variations in the effects of chronic ethanol administration on GABA(A) receptor expression: potential mechanisms. Neurochem Int. 2000 ; 37: 453-461 (Pubitemid 30386983)
19. Gousias IS, Rueckert D, Heckemann RA, Dyet LE, Boardman JP, Edwards AD, et al. Automatic segmentation of brain MRIs of 2-year-olds into 83 regions of interest. Neuroimage. 2008 ; 40: 672-684
20. Hadingham KL, Wingrove P, Le , Bourdelles B, Palmer KJ, Ragan CI, Whiting PJ. Cloning of cDNA sequences encoding human alpha 2 and alpha 3 gamma-aminobutyric acidA receptor subunits and characterization of the benzodiazepine pharmacology of recombinant alpha 1-, alpha 2-, alpha 3-, and alpha 5-containing human gamma-aminobutyric acidA receptors. Mol Pharmacol. 1993 ; 43: 970-975 (Pubitemid 23178875)
21. Hammers A, Allom R, Koepp MJ, Free SL, Myers R, Lemieux L, et al. Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe. Hum Brain Mapp. 2003 ; 19: 224-247 (Pubitemid 36959351)
22. June HL, Harvey SC, Foster KL, McKay PF, Cummings R, Garcia M, et al. GABA(A) receptors containing (alpha)5 subunits in the CA1 and CA3 hippocampal fields regulate ethanol-motivated behaviors: an extended ethanol reward circuitry. J Neurosci. 2001 ; 21: 2166-2177 (Pubitemid 32221399)
23. Krystal JH, Staley J, Mason G, Petrakis IL, Kaufman J, Harris RA, et al. Gamma-aminobutyric acid type A receptors and alcoholism: intoxication, dependence, vulnerability, and treatment. Arch Gen Psychiatry. 2006 ; 63: 957-968 (Pubitemid 44330454)
24. Lingford-Hughes AR, Acton PD, Gacinovic S, Suckling J, Busatto GF, Boddington SJA, et al. Reduced levels of the GABA-benzodiazepine receptor in alcohol dependency in the absence of grey matter atrophy. Br J Psychiatry. 1998 ; 173: 16-122
25. C]Ro15 4513 positron emission tomography. J Cereb Blood Flow Metab. 2002 ; 22: 878-889 (Pubitemid 34747605)
26. C-flumazenil PET and pharmacodynamic study. Psychopharmacology. 2005 ; 180: 595-606 (Pubitemid 41317856)
27. C]Ro15-4513 using positron emission tomography. Synapse. 2003 ; 47: 200-208 (Pubitemid 36056833)
28. Makris N, Oscar-Berman M, Jaffin SK, Hodge SM, Kennedy DN, Caviness VS, et al. Decreased volume of the brain reward system in alcoholism. Biol Psychiatry. 2008 ; 64: 192-202
29. A-receptor containing alpha5 subunit antagonizes ethanol's neurobehavioural effects in Long-Evans rats. Psychopharmacology. 2004 ; 172: 455-462 (Pubitemid 38650983)
30. Mechtcheriakov S, Brenneis C, Egger K, Koppelstaetter F, Schocke M, Marksteiner J. A widespread distinct pattern of cerebral atrophy in patients with alcohol addiction revealed by voxel-based morphometry. J Neurol Neurosurg Psychiatry. 2007 ; 78: 610-614 (Pubitemid 46853896)
31. Meyer JH, Gunn RN, Myers R, Grasby PM. Assessment of spatial normalization of PET ligand images using ligand-specific templates. Neuroimage. 1999 ; 9: 545-553 (Pubitemid 29372222)
32. Mhatre M, Mehta AK, Ticku MK. Chronic ethanol administration increases the binding of the benzodiazepine inverse agonist and alcohol antagonist [3H]RO15-4513 in rat brain. Eur J Pharmacol. 1988 ; 153: 141-145
33. Nutt DJ, Besson M, Wilson SJ, Dawson GR, Lingford-Hughes AR. Selective blockade of alcohol's amnestic actions by an α5 subtype- benzodiazepine receptor inverse agonist. Neuropharmacology. 2007 ; 53: 810-820 (Pubitemid 350123479)
34. Pickering C, Avesson L, Lindblom J, Liljequist S, Schiöth HB. Identification of neurotransmitter receptor genes involved in alcohol self-administration in the rat prefrontal cortex, hippocampus and amygdala. Prog Neuropsychopharm Biol Psych. 2007 ; 31: 53-64 (Pubitemid 44959239)
35. Pirker S, Schwarzer C, Wieselthaler A, Sieghart W, Sperk G. GABA(A) receptors: immunocytochemical distribution of 13 subunits in the adult rat brain. Neuroscience. 2000 ; 101: 815-850
36. A receptor subtypes to the discriminative stimulus effects of ethanol in squirrel monkeys. J Pharmacol Exp Ther. 2005 ; 313: 658-667 (Pubitemid 40604166)
37. Robb RA, Hanson DP. A software system for interactive and quantitative visualization of multidimensional biomedical images. Australas Phys Eng Sci Med. 1991 ; 14: 9-30
38. A receptor function and dissection of the pharmacology of benzodiazepines and general anesthetics through mouse genetics. Annu Rev Pharmacol Toxicol. 2004 ; 44: 475-498 (Pubitemid 38263850)
39. Savic MM, Obradovic DI, Ugrei ND, Bokonji DR. Memory effects of benzodiazepines: memory stages and types versus binding-site subtypes. Neural Plast. 2005 ; 12: 289-298 (Pubitemid 43072005)
40. Spielberger C, Gorsuch RL, Lushene RE Manual for the state-trait anxiety inventory. Palo Alto: Consulting Psychologist Press ; 1970 :
41. Spinks TJ, Jones T, Bloomfield PM, Bailey DL, Miller M, Hogg D, et al. Physical characteristics of the ECAT EXACT3D positron tomograph. Phys Med Biol. 2000 ; 45: 2601-2618
42. Staley JK, Gottschalk C, Petrakis IL, Gueorguieva R, O'Malley S, Baldwin R, et al. Cortical gamma-aminobutyric acid type A-benzodiazepine receptors in recovery from alcohol dependence: relationship to features of alcohol dependence and cigarette smoking. Arch Gen Psychiatry. 2005 ; 62: 877-888 (Pubitemid 41126882)
43. A alpha5-containing receptors in ethanol reward: the effects of targeted gene deletion, and a selective inverse agonist. Eur J Pharmacol. 2005 ; 526: 240-250 (Pubitemid 41744121)
44. Sternfeld F, Carling RW, Jelley RA, Ladduwahetty T, Merchant KJ, Moore KW, et al. Selective, orally active gamma-aminobutyric acidA alpha5 receptor inverse agonists as cognition enhancers. J Med Chem. 2004 ; 47: 2176-2179 (Pubitemid 38478841)
45. Stockwell T, Murphy D, Hodgson R. The severity of alcohol dependence questionnaire: its use, reliability and validity. Br J Addict. 1983 ; 78: 145-155 (Pubitemid 13096761)
46. Sullivan EV, Deshmukh A, De Rosa E, Rosenbloom MJ, Pfefferbaum A. Striatal and forebrain nuclei volumes: contribution to motor function and working memory deficits in alcoholism. Biol Psychiatry. 2005 ; 57: 768-776 (Pubitemid 40487921)
47. Sullivan EV, Marsh L, Mathalon DH, Lim KO, Pfefferbaum A. Anterior hippocampal volume deficits in nonamnesic, aging chronic alcoholics. Alcohol Clin Exp Res. 1995 ; 19: 110-122
48. Toso L, Roberson R, Woodard J, Abebe D, Spong CY. Prenatal alcohol exposure alters GABA(A)alpha5 expression: a mechanism of alcohol-induced learning dysfunction. Am J Obstet Gynecol. 2006 ; 195: 522-527 (Pubitemid 44142375)
49. A receptor subtype. J Neurosci. 1997 ; 17: 2728-2737 (Pubitemid 27155006)
50. Turkheimer F, Moresco RM, Lucignani G, Sokoloff L, Fazio F, Schmidt K. The use of spectral analysis to determine regional cerebral glucose utilization with positron emission tomography and [18F]fluorodeoxyglucose: theory, implementation, and optimization procedures. J Cereb Blood Flow Metab. 1994 ; 14: 406-422
51. Turkheimer FE, Smith CB, Schmidt K. Estimation of the number of "true" null hypotheses in multivariate analysis of neuroimaging data. Neuroimage. 2001 ; 13: 920-930 (Pubitemid 32848336)
52. A receptors are reversed by the behavioral alcohol antagonist Ro15-4513. Proc Natl Acad Sci USA. 2006 ; 103: 8540-8545 (Pubitemid 43838491)
53. Wechsler D WAIS-R manual. New York: The Psychological Corporation ; 1981
54. Wechsler D (1987) The Wechster Memory Scale-revised. The Psychological Coporation, Harcourt Brace Jovanovich, Inc.