Neurochemical imaging of addictive disorders

Neuromethods

Volumn 71, Issue , 2012, Pages 249-271

  Broft, Allegra ^a   Martinez, Diana ^a  

^a Department of Medicine   (United States)

Author keywords

Addiction; Dopamine; Neurochemical imaging; PET; Reward; SPECT

Indexed keywords

3 METHYLSPIPERONE F 18; 3,4 METHYLENEDIOXYMETHAMPHETAMINE; 4 AMINOBUTYRIC ACID A RECEPTOR; 4 AMINOBUTYRIC ACID RECEPTOR; 5 (7 BENZOFURANYL) 8 CHLORO 2,3,4,5 TETRAHYDRO 7 HYDROXY 3 METHYL 1H 3 BENZAZEPINE; 5 (7 BENZOFURANYL) 8 CHLORO 2,3,4,5 TETRAHYDRO 7 HYDROXY 3 METHYL 1H 3 BENZAZEPINE C 11; 6 FLUORODOPA F 18; 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; CARFENTANIL C 11; COCAINE; COCAINE C 11; DIAMORPHINE; DIPRENORPHINE C 11; DOPAMINE; DOPAMINE 1 RECEPTOR; DOPAMINE 2 RECEPTOR; EPIDEPRIDE; EPIDEPRIDE I 131; FLUMAZENIL C 11; FLUORODEOXYGLUCOSE F 18; LEVODOPA; METHAMPHETAMINE; OPIATE RECEPTOR; RACLOPRIDE C 11; THREOMETHYLPHENIDATE C 11; TRACER; UNCLASSIFIED DRUG; UNINDEXED DRUG; VESICULAR MONOAMINE TRANSPORTER; VESICULAR MONOAMINE TRANSPORTER 2;

ALCOHOLISM; ARTICLE; CLINICAL RESEARCH; COCAINE DEPENDENCE; DOPAMINERGIC SYSTEM; DRUG DEPENDENCE; GABAERGIC SYSTEM; HUMAN; LIMBIC SYSTEM; NEUROCHEMISTRY; NEUROIMAGING; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; REWARD; SEROTONINERGIC SYSTEM; SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY;

EID: 84867551098     PISSN: 08932336     EISSN: 19406045     Source Type: Book Series    
DOI: 10.1007/7657-2012-48     Document Type: Article

References (119)

1. Volkow ND, Fowler JS, Wolf AP, Schlyer D, Shiue CY, Alpert R, Dewey SL, Logan J, Bendriem B, Christman D et al (1990) Effects of chronic cocaine abuse on postsynaptic dopamine receptors. Am J Psychiatry 147:719-724
2. Volkow ND, Fowler JS,Wang GJ, Hitzemann R, Logan J, Schlyer DJ, Dewey SL, Wolf AP (1993) Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers. Synapse 14:169-177
3. Volkow ND, Wang GJ, Fowler JS, Logan J, Gatley SJ, Hitzemann R, Chen AD, Dewey SL, Pappas N (1997) Decreased striatal dopaminergic responsiveness in detoxified cocainedependent subjects. Nature 386:830-833
4. Martinez D, Broft A, Foltin RW, Slifstein M, Hwang DR, Huang Y, Perez A, Frankle WG, Cooper T, Kleber HD, Fischman MW, Laruelle M (2004) Cocaine dependence and d2 receptor availability in the functional subdivisions of the striatum: relationship with cocaine-seeking behavior. Neuropsychopharmacology 29:1190-1202
5. Martinez D, Greene K, Broft A, Kumar D, Liu F, Narendran R, Slifstein M, Van Heertum R, Kleber HD (2009) Lower level of endogenous dopamine in patients with cocaine dependence: findings from PET imaging of D(2)/D(3) receptors following acute dopamine depletion. Am J Psychiatry 166:1170-1177
6. Martinez D, Carpenter KM, Liu F, Slifstein M, Broft A, Friedman AC, Kumar D, Van Heertum R, Kleber HD, Nunes E (2011) Imaging dopamine transmission in cocaine dependence: response to treatment linked to neurochemistry. Am J Psychiatry 168 (6):634-641
7. Farfel GM, Kleven MS, Woolverton WL, Seiden LS, Perry BD (1992) Effects of repeated injections of cocaine on catecholamine receptor binding sites, dopamine transporter binding sites and behavior in rhesus monkey. Brain Res 578:235-243
8. Moore RJ, Vinsant SL, Nader MA, Porrino LJ, Friedman DP (1998) Effect of cocaine self-administration on dopamine D2 receptors in rhesus monkeys. Synapse 30:88-96
9. Nader MA, Daunais JB, Moore T, Nader SH, Moore RJ, Smith HR, Friedman DP, Porrino LJ (2002) Effects of cocaine selfadministration on striatal dopamine systems in rhesus monkeys: initial and chronic exposure. Neuropsychopharmacology 27:35-46
10. Nader MA, Morgan D, Gage HD, Nader SH, Calhoun TL, Buchheimer N, Ehrenkaufer R, Mach RH (2006) PET imaging of dopamine D2 receptors during chronic cocaine selfadministration in monkeys. Nat Neurosci 9:1050-1056
11. Volkow ND, Wang GJ, Fowler JS, Logan J, Gatley SJ, Gifford A, Hitzemann R, Ding YS, Pappas N (1999) Prediction of reinforcing responses to psychostimulants in humans by brain dopamine D2 receptor levels. Am J Psychiatry 156:1440-1443
12. Volkow ND,Wang GJ, Fowler JS, Thanos PP, Logan J, Gatley SJ, Gifford A, Ding YS,Wong C, Pappas N (2002) Brain DA D2 receptors predict reinforcing effects of stimulants in humans: replication study. Synapse 46:79-82
13. Morgan D, Grant KA, Gage HD, Mach RH, Kaplan JR, Prioleau O, Nader SH, Buchheimer N, Ehrenkaufer RL, Nader MA (2002) Social dominance in monkeys: dopamine D2 receptors and cocaine self-administration. Nat Neurosci 5:169-174
14. Thanos PK, Michaelides M, Umegaki H, Volkow ND (2008) D2R DNA transfer into the nucleus accumbens attenuates cocaine self-administration in rats. Synapse 62:481-486
15. Dalley JW, Fryer TD, Brichard L, Robinson ES, Theobald DE, Laane K, Pena Y, Murphy ER, Shah Y, Probst K, Abakumova I, Aigbirhio FI, Richards HK, Hong Y, Baron JC, Everitt BJ, Robbins TW (2007) Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement. Science 315:1267-1270
16. Asensio S, Romero MJ, Romero FJ, Wong C, Alia-Klein N, Tomasi D, Wang GJ, Telang F, Volkow ND, Goldstein RZ (2010) Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later. Synapse 64:397-402
17. Laruelle M (2000) Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review. J Cereb Blood Flow Metab 20:423-451
18. Skinbjerg M, Liow JS, Seneca N, Hong J, Lu S, Thorsell A, Heilig M, Pike VW, Halldin C, Sibley DR, Innis RB (2010) D2 dopamine receptor internalization prolongs the decrease of radioligand binding after amphetamine: a PET study in a receptor internalizationdeficient mouse model. Neuroimage 50:1402-1407
19. Malison RT, Mechanic KY, Klummp H, Baldwin RM, Kosten TR, Seibyl JP, Innis RB (1999) Reduced amphetamine-stimulated dopamine release in cocaine addicts as measured by [123I]IBZM SPECT. J Nucl Med 40:110P
20. Martinez D, Narendran R, Foltin RW, Slifstein M, Hwang DR, Broft A, Huang Y, Cooper TB, Fischman MW, Kleber HD, Laruelle M (2007) Amphetamine-induced dopamine release: markedly blunted in cocaine dependence and predictive of the choice to self-administer cocaine. Am J Psychiatry 164:622-629
21. Sesack SR, Grace AA (2010) Cortico-Basal Ganglia reward network: microcircuitry. Neuropsychopharmacology 35:27-47
22. Goto Y, Grace AA (2008) Limbic and cortical information processing in the nucleus accumbens. Trends Neurosci 31:552-558
23. Cardinal RN, Pennicott DR, Sugathapala CL, Robbins TW, Everitt BJ (2001) Impulsive choice induced in rats by lesions of the nucleus accumbens core. Science 292:2499-2501
24. Dietrich JB, Mangeol A, Revel MO, Burgun C, Aunis D, Zwiller J (2005) Acute or repeated cocaine administration generates reactive oxygen species and induces antioxidant enzyme activity in dopaminergic rat brain structures. Neuropharmacology 48:965-974
25. Cunha-Oliveira T, Rego AC, Oliveira CR (2008) Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs. Brain Res Rev 58:192-208
26. Volkow ND, Wang GJ, Telang F, Fowler JS, Logan J, Childress AR, Jayne M, Ma Y,Wong C (2006) Cocaine cues and dopamine in dorsal striatum: mechanism of craving in cocaine addiction. J Neurosci 26:6583-6588
27. Volkow ND, Wang GJ, Telang F, Fowler JS, Logan J, Childress AR, Jayne M, Ma Y,Wong C (2008) Dopamine increases in striatum do not elicit craving in cocaine abusers unless they are coupled with cocaine cues. Neuroimage 39:1266-1273
28. Wong DF, Kuwabara H, Schretlen DJ, Bonson KR, Zhou Y, Nandi A, Brasic JR, Kimes AS, Maris MA, Kumar A, Contoreggi C, Links J, Ernst M, Rousset O, Zukin S, Grace AA, Lee JS, Rohde C, Jasinski DR, Gjedde A, London ED (2006) Increased occupancy of dopamine receptors in human striatum during cue-elicited cocaine craving. Neuropsychopharmacology 31:2716-2727
29. Laruelle M, D'Souza CD, Baldwin RM, Abi- Dargham A, Kanes SJ, Fingado CL, Seibyl JP, Zoghbi SS, BowersMB, Jatlow P, Charney DS, Innis RB (1997) Imaging D2 receptor occupancy by endogenous dopamine in humans. Neuropsychopharmacology 17:162-174
30. Abi-Dargham A, Rodenhiser J, Printz D, Zea- Ponce Y, Gil R, Kegeles LS, Weiss R, Cooper TB, Mann JJ, Van Heertum RL, Gorman JM, Laruelle M (2000) Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci U S A 97:8104-8109
31. Verhoeff NP, Kapur S, Hussey D, Lee M, Christensen B, Psych C, Papatheodorou G, Zipursky RB (2001) A simple method to measure baseline occupancy of neostriatal dopamine D2 receptors by dopamine in vivo in healthy subjects. Neuropsychopharmacology 25:213-223
32. Verhoeff NP, Hussey D, Lee M, Tauscher J, Papatheodorou G, Wilson AA, Houle S, Kapur S (2002) Dopamine depletion results in increased neostriatal D(2), but not D(1), receptor binding in humans. Mol Psychiatry 7 (233):322-328
33. Self DW, Barnhart WJ, Lehman DA, Nestler EJ (1996) Opposite modulation of cocaineseeking behavior by D1- and D2-like dopamine receptor agonists. Science 271:1586-1589
34. Self DW, Karanian DA, Spencer JJ (2000) Effects of the novel D1 dopamine receptor agonist ABT-431 on cocaine selfadministration and reinstatement. Ann N Y Acad Sci 909:133-144
35. Martinez D, Slifstein M, Narendran R, Foltin RW, Broft A, Hwang DR, Perez A, Abi- Dargham A, Fischman MW, Kleber HD, Laruelle M (2009) Dopamine D1 receptors in cocaine dependence measured with PET and the choice to self-administer cocaine. Neuropsychopharmacology 34:1774-1782
36. Malison RT, Best SE, van Dyck CH, McCance EF, Wallace EA, Laruelle M, Baldwin RM, Seibyl JP, Price LH, Kosten TR, Innis RB (1998) Elevated striatal dopamine transporters during acute cocaine abstinence as measured by [123I] beta-CIT SPECT. Am J Psychiatry 155:832-834
37. Volkow ND, Wang GJ, Fowler JS, Logan J, Hitzemannn R, Gatley SJ, MacGregor RR, Wolf AP (1996) Cocaine uptake is decreased in the brain of detoxified cocaine abusers. Neuropsychopharmacology 14:159-168
38. Wang GJ, Volkow ND, Fowler JS, Fischman M, Foltin R, Abumrad NN, Logan J, Pappas NR (1997) Cocaine abusers do not show loss of dopamine transporters with age. Life Sci 61:1059-1065
39. Wu JC, Bell K, Najafi A, Widmark C, Keator D, Tang C, Klein E, Bunney BG, Fallon J, Bunney WE (1997) Decreasing striatal 6- FDOPA uptake with increasing duration of cocaine withdrawal. Neuropsychopharmacology 17:402-409
40. Gawin FH, Kleber HD (1986) Abstinence symptomatology and psychiatric diagnosis in cocaine abusers. Clinical observations. Arch Gen Psychiatry 43:107-113
41. Satel SL, Price LH, Palumbo JM, McDougle CJ, Krystal JH, Gawin F, Charney DS, Heninger GR, Kleber HD (1991) Clinical phenomenology and neurobiology of cocaine abstinence: a prospective inpatient study. Am J Psychiatry 148:1712-1716
42. Volkow ND, Hitzemann R, Wang GJ, Fowler JS, Wolf AP, Dewey SL, Handlesman L (1992) Long-term frontal brain metabolic changes in cocaine abusers. Synapse 11:184-190
43. Zubieta JK, Gorelick DA, Stauffer R, Ravert HT, Dannals RF, Frost JJ (1996) Increased mu opioid receptor binding detected by PET in cocaine-dependent men is associated with cocaine craving. Nat Med 2:1225-1229
44. Gorelick DA, Kim YK, Bencherif B, Boyd SJ, Nelson R, Copersino M, Endres CJ, Dannals RF, Frost JJ (2005) Imaging brain mu-opioid receptors in abstinent cocaine users: time course and relation to cocaine craving. Biol Psychiatry 57:1573-1582
45. Jacobsen LK, Staley JK, Malison RT, Zoghbi SS, Seibyl JP, Kosten TR, Innis RB (2000) Elevated central serotonin transporter binding availability in acutely abstinent cocainedependent patients. Am J Psychiatry 157:1134-1140
46. Banks ML, Czoty PW, Gage HD, Bounds MC, Garg PK, Garg S, Nader MA (2008) Effects of cocaine and MDMA selfadministration on serotonin transporter availability in monkeys. Neuropsychopharmacology 33:219-225
47. Harvey DC, Lacan G, Melegan WP (2000) Regional heterogeneity of dopaminergic deficits in vervet monkey striatum and substantia nigra after methamphetamine exposure. Exp Brain Res 133:349-358
48. Itzhak Y, Martin JL, Ali SF, Norenberg MD (1997) Depletion of striatal dopamine transporter does not affect psychostimulantinduced locomotor activity. Neuroreport 8:3245-3249
49. Ricaurte GA, Guillery RW, Seiden LS, Schuster CR, Moore RY (1982) Dopamine nerve terminal degeneration produced by high doses of methylamphetamine in the rat brain. Brain Res 235:93-103
50. Seiden LS, Woolverton WL, Lorens SA, Williams JE, Corwin RL, Hata N, Olimski M (1993) Behavioral consequences of partial monoamine depletion in the CNS after methamphetamine-like drugs: the conflict between pharmacology and toxicology. NIDA Res Monogr 136:34-46; discussion 46-52
51. Woolverton WL, Ricaurte GA, Forno LS, Seiden LS (1989) Long-term effects of chronic methamphetamine administration in rhesus monkeys. Brain Res 486:73-78
52. Melega WP, Raleigh MJ, Stout DB, Lacan G, Huang SC, Phelps ME (1997) Recovery of striatal dopamine function after acute amphetamine- and methamphetamineinduced neurotoxicity in the vervet monkey. Brain Res 766:113-120
53. Harvey DC, Lacan G, Tanious SP, Melega WP (2000) Recovery from methamphetamine induced long-term nigrostriatal dopaminergic deficits without substantia nigra cell loss. Brain Res 871:259-270
54. Melega WP, Lacan G, Harvey DC, Huang SC, Phelps ME (1998) Dizocilpine and reduced body temperature do not prevent methamphetamine-induced neurotoxicity in the vervet monkey: [11C]WIN 35,428-positron emission tomography studies. Neurosci Lett 258:17-20
55. Villemagne V, Yuan J, Wong DF, Dannals RF, Hatzidimitriou G, Mathews WB, Ravert HT, Musachio J, McCann UD, Ricaurte GA (1998) Brain dopamine neurotoxicity in baboons treated with doses of methamphetamine comparable to those recreationally abused by humans: evidence from [11C] WIN-35,428 positron emission tomography studies and direct in vitro determinations. J Neurosci 18:419-427
56. Melega WP, Lacan G, Desalles AA, Phelps ME (2000) Long-term methamphetamineinduced decreases of [(11)C]WIN 35,428 binding in striatum are reduced by GDNF: PET studies in the vervet monkey. Synapse 35:243-249
57. Hashimoto K, Tsukada H, Nishiyama S, Fukumoto D, Kakiuchi T, Iyo M (2007) Protective effects of minocycline on the reduction of dopamine transporters in the striatum after administration of methamphetamine: a positron emission tomography study in conscious monkeys. Biol Psychiatry 61:577-581
58. Hashimoto K, Tsukada H, Nishiyama S, Fukumoto D, Kakiuchi T, Shimizu E, Iyo M (2004) Protective effects of N-acetyl-L-cysteine on the reduction of dopamine transporters in the striatum of monkeys treated with methamphetamine. Neuropsychopharmacology 29:2018-2023
59. Johanson CE, Frey KA, Lundahl LH, Keenan P, Lockhart N, Roll J, Galloway GP, Koeppe RA, Kilbourn MR, Robbins T, Schuster CR (2006) Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers. Psychopharmacology (Berl) 185 (3):327-338
60. McCann UD, Kuwabara H, Kumar A, Palermo M, Abbey R, Brasic J, Ye W, Alexander M, Dannals RF, Wong DF, Ricaurte GA (2008) Persistent cognitive and dopamine transporter deficits in abstinent methamphetamine users. Synapse 62:91-100
61. McCann UD, Wong DF, Yokoi F, Villemagne V, Dannals RF, Ricaurte GA (1998) Reduced striatal dopamine transporter density in abstinent methamphetamine and methcathinone users: evidence from positron emission tomography studies with [11C]WIN-35,428. J Neurosci 18:8417-8422
62. Iyo M, Sekine Y, Mori N (2004) Neuromechanism of developing methamphetamine psychosis: a neuroimaging study. Ann N Y Acad Sci 1025:288-295
63. Volkow ND, Chang L, Wang GJ, Fowler JS, Franceschi D, Sedler M, Gatley SJ, Miller E, Hitzemann R, Ding YS, Logan J (2001) Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence. J Neurosci 21:9414-9418
64. Sekine Y, Iyo M, Ouchi Y, Matsunaga T, Tsukada H, Okada H, Yoshikawa E, Futatsubashi M, Takei N, Mori N (2001) Methamphetamine-related psychiatric symptoms and reduced brain dopamine transporters studied with PET. Am J Psychiatry 158:1206-1214
65. Chou YH, Huang WS, Su TP, Lu RB,Wan FJ, Fu YK (2007) Dopamine transporters and cognitive function in methamphetamine abuser after a short abstinence: a SPECT study. Eur Neuropsychopharmacol 17:46-52
66. Volkow ND, Chang L, Wang GJ, Fowler JS, Leonido-Yee M, Franceschi D, Sedler MJ, Gatley SJ, Hitzemann R, Ding YS, Logan J, Wong C, Miller EN (2001) Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. Am J Psychiatry 158:377-382
67. Volkow ND, Chang L, Wang GJ, Fowler JS, Ding YS, Sedler M, Logan J, Franceschi D, Gatley J, Hitzemann R, Gifford A, Wong C, Pappas N (2001) Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex. Am J Psychiatry 158:2015-2021
68. Lee B, London ED, Poldrack RA, Farahi J, Nacca A, Monterosso JR, Mumford JA, Bokarius AV, Dahlbom M, Mukherjee J, Bilder RM, Brody AL, Mandelkern MA (2009) Striatal dopamine d2/d3 receptor availability is reduced in methamphetamine dependence and is linked to impulsivity. J Neurosci 29:14734-14740
69. Sekine Y, Ouchi Y, Takei N, Yoshikawa E, Nakamura K, Futatsubashi M, Okada H, Minabe Y, Suzuki K, Iwata Y, Tsuchiya KJ, Tsukada H, Iyo M, Mori N (2006) Brain serotonin transporter density and aggression in abstinent methamphetamine abusers. Arch Gen Psychiatry 63:90-100
70. Kish SJ, Fitzmaurice PS, Boileau I, Schmunk GA, Ang LC, Furukawa Y, Chang LJ, Wickham DJ, Sherwin A, Tong J (2009) Brain serotonin transporter in human methamphetamine users. Psychopharmacology (Berl) 202:649-661
71. Hietala J, West C, Syvalahti E, Nagren K, Lehikoinen P, Sonninen P, Ruotsalainen U (1994) Striatal D2 dopamine receptor binding characteristics in vivo in patients with alcohol dependence. Psychopharmacology (Berl) 116:285-290
72. Volkow ND, Wang GJ, Fowler JS, Logan J, Hitzemann R, Ding YS, Pappas N, Shea C, Piscani K (1996) Decreases in dopamine receptors but not in dopamine transporters in alcoholics. Alcohol Clin Exp Res 20:1594-1598
73. Volkow ND,Wang GJ, Maynard L, Fowler JS, Jayne B, Telang F, Logan J, Ding YS, Gatley SJ, Hitzemann R, Wong C, Pappas N (2002) Effects of alcohol detoxification on dopamine D2 receptors in alcoholics: a preliminary study. Psychiatry Res 116:163-172
74. Heinz A, Siessmeier T, Wrase J, Hermann D, Klein S, Grusser SM, Flor H, Braus DF, Buchholz HG, Grunder G, Schreckenberger M, Smolka MN, Rosch F, Mann K, Bartenstein P (2004) Correlation between dopamine D (2) receptors in the ventral striatum and central processing of alcohol cues and craving. Am J Psychiatry 161:1783-1789
75. Heinz A, Siessmeier T, Wrase J, Buchholz HG, Grunder G, Kumakura Y, Cumming P, Schreckenberger M, Smolka MN, Rosch F, Mann K, Bartenstein P (2005) Correlation of alcohol craving with striatal dopamine synthesis capacity and D2/3 receptor availability: a combined [18F]DOPA and [18F]DMFP PET study in detoxified alcoholic patients. Am J Psychiatry 162:1515-1520
76. Martinez D, Gil R, Slifstein M, Hwang DR, Huang Y, Perez A, Kegeles L, Talbot P, Evans S, Krystal J, Laruelle M, Abi-Dargham A (2005) Alcohol dependence is associated with blunted dopamine transmission in the ventral striatum. Biol Psychiatry 58:779-786
77. Repo E, Kuikka JT, Bergstrom KA, Karhu J, Hiltunen J, Tiihonen J (1999) Dopamine transporter and D2-receptor density in lateonset alcoholism. Psychopharmacology (Berl) 147:314-318
78. Guardia J, Catafau AM, Batlle F, Martin JC, Segura L, Gonzalvo B, Prat G, Carrio I, Casas M (2000) Striatal dopaminergic D(2) receptor density measured by [(123)I]iodobenzamide SPECT in the prediction of treatment outcome of alcohol-dependent patients. Am J Psychiatry 157:127-129
79. Volkow ND, Wang GJ, Begleiter H, Porjesz B, Fowler JS, Telang F,Wong C, Ma Y, Logan J, Goldstein R, Alexoff D, Thanos PK (2006) High levels of dopamine D2 receptors in unaffected members of alcoholic families: possible protective factors. Arch Gen Psychiatry 63:999-1008
80. Thanos PK, Rivera SN, Weaver K, Grandy DK, Rubinstein M, Umegaki H, Wang GJ, Hitzemann R, Volkow ND (2005) Dopamine D2R DNA transfer in dopamine D2 receptordeficient mice: effects on ethanol drinking. Life Sci 77:130-139
81. Bice PJ, Liang T, Zhang L, Strother WN, Carr LG (2008) Drd2 expression in the high alcohol-preferring and low alcohol-preferring mice. Mamm Genome 19:69-76
82. Thanos PK, Volkow ND, Freimuth P, Umegaki H, Ikari H, Roth G, Ingram DK, Hitzemann R (2001) Overexpression of dopamine D2 receptors reduces alcohol selfadministration. J Neurochem 78:1094-1103
83. Volkow ND, Wang GJ, Telang F, Fowler JS, Logan J, Jayne M, Ma Y, Pradhan K, Wong C (2007) Profound decreases in dopamine release in striatum in detoxified alcoholics: possible orbitofrontal involvement. J Neurosci 27:12700-12706
84. Tiihonen J, Vilkman H, Rasanen P, Ryynanen OP, Hakko H, Bergman J, Hamalainen T, Laakso A, Haaparanta-Solin M, Solin O, Kuoppamaki M, Syvalahti E, Hietala J (1998) Striatal presynaptic dopamine function in type 1 alcoholics measured with positron emission tomography. Mol Psychiatry 3:156-161
85. Gilman S, Koeppe RA, Adams KM, Junck L, Kluin KJ, Johnson-Greene D, Martorello S, Heumann M, Bandekar R (1998) Decreased striatal monoaminergic terminals in severe chronic alcoholism demonstrated with (+) [11C]dihydrotetrabenazine and positron emission tomography. Ann Neurol 44:326-333
86. Tiihonen J, Kuikka J, Bergstrom K, Hakola P, Karhu J, Ryynanen OP, Fohr J (1995) Altered striatal dopamine re-uptake site densities in habitually violent and non-violent alcoholics. Nat Med 1:654-657
87. Laine TP, Ahonen A, Rasanen P, Tiihonen J (1999) Dopamine transporter availability and depressive symptoms during alcohol withdrawal. Psychiatry Res 90:153-157
88. Heinz A, Goldman D, Jones DW, Palmour R, Hommer D, Gorey JG, Lee KS, Linnoila M, Weinberger DR (2000) Genotype influences in vivo dopamine transporter availability in human striatum. Neuropsychopharmacology 22:133-139
89. Gilman S, Koeppe RA, Adams K, Johnson- Greene D, Junck L, Kluin KJ, Brunberg J, Martorello S, Lohman M (1996) Positron emission tomographic studies of cerebral benzodiazepine-receptor binding in chronic alcoholics. Ann Neurol 40:163-171
90. Abi-Dargham A, Krystal JH, Anjilvel S, Scanley BE, Zoghbi S, Baldwin RM, Rajeevan N, Ellis S, Petrakis IL, Seibyl JP, Charney DS, Laruelle M, Innis RB (1998) Alterations of benzodiazepine receptors in type II alcoholic subjects measured with SPECT and [123I] iomazenil. Am J Psychiatry 155:1550-1555
91. Lingford-Hughes AR, Acton PD, Gacinovic S, Suckling J, Busatto GF, Boddington SJ, Bullmore E, Woodruff PW, Costa DC, Pilowsky LS, Ell PJ, Marshall EJ, Kerwin RW (1998) Reduced levels of GABAbenzodiazepine receptor in alcohol dependency in the absence of grey matter atrophy. Br J Psychiatry 173:116-122
92. Jalan R, Turjanski N, Taylor-Robinson SD, Koepp MJ, Richardson MP, Wilson JA, Bell JD, Brooks DJ (2000) Increased availability of central benzodiazepine receptors in patients with chronic hepatic encephalopathy and alcohol related cirrhosis. Gut 46:546-552
93. Staley JK, Gottschalk C, Petrakis IL, Gueorguieva R, O'Malley S, Baldwin R, Jatlow P, Verhoeff NP, Perry E, Weinzimmer D, Frohlich E, Ruff E, van Dyck CH, Seibyl JP, Innis RB, Krystal JH (2005) Cortical gammaaminobutyric acid type A-benzodiazepine receptors in recovery from alcohol dependence: relationship to features of alcohol dependence and cigarette smoking. Arch Gen Psychiatry 62:877-888
94. Litton JE, Neiman J, Pauli S, Farde L, Hindmarsh T, Halldin C, Sedvall G (1993) PET analysis of [11C]flumazenil binding to benzodiazepine receptors in chronic alcoholdependent men and healthy controls. Psychiatry Res 50:1-13
95. Lingford-Hughes AR, Acton PD, Gacinovic S, Boddington SJ, Costa DC, Pilowsky LS, Ell PJ, Marshall EJ, Kerwin RW (2000) Levels of gamma-aminobutyric acid-benzodiazepine receptors in abstinent, alcohol-dependent women: preliminary findings from an 123I-iomazenil single photon emission tomography study. Alcohol Clin Exp Res 24:1449-1455
96. Lingford-Hughes A, Reid AG, Myers J, Feeney A, Hammers A, Taylor L, Rosso L, Turkheimer F, Brooks DJ, Grasby P, Nutt DJ (2012) A [11c]Ro15 4513 PET study suggests that alcohol dependence in man is associated with reduced {alpha}5 benzodiazepine receptors in limbic regions. J Psychopharmacol 26(2):273-281
97. Heinz A, Reimold M, Wrase J, Hermann D, Croissant B, Mundle G, Dohmen BM, Braus DF, Schumann G, Machulla HJ, Bares R, Mann K (2005) Correlation of stable elevations in striatal mu-opioid receptor availability in detoxified alcoholic patients with alcohol craving: a positron emission tomography study using carbon 11-labeled carfentanil. Arch Gen Psychiatry 62:57-64
98. Bencherif B,Wand GS, McCaul ME, Kim YK, Ilgin N, Dannals RF, Frost JJ (2004) Muopioid receptor binding measured by [11C] carfentanil positron emission tomography is related to craving and mood in alcohol dependence. Biol Psychiatry 55:255-262
99. Williams TM, Davies SJ, Taylor LG, Daglish MR, Hammers A, Brooks DJ, Nutt DJ, Lingford-Hughes A (2009) Brain opioid receptor binding in early abstinence from alcohol dependence and relationship to craving: an [11C]diprenorphine PET study. Eur Neuropsychopharmacol 19:740-748
100. Weerts EM, Kim YK, Wand GS, Dannals RF, Lee JS, Frost JJ, McCaul ME (2008) Differences in delta- and mu-opioid receptor blockade measured by positron emission tomography in naltrexone-treated recently abstinent alcohol-dependent subjects. Neuropsychopharmacology 33:653-665
101. Heinz A, Jones DW, Mazzanti C, Goldman D, Ragan P, Hommer D, Linnoila M, Weinberger DR (2000) A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity. Biol Psychiatry 47:643-649
102. Heinz A, Ragan P, Jones DW, Hommer D, Williams W, Knable MB, Gorey JG, Doty L, Geyer C, Lee KS, Coppola R, Weinberger DR, LinnoilaM(1998) Reduced central serotonin transporters in alcoholism. Am J Psychiatry 155:1544-1549
103. Szabo Z, Owonikoko T, Peyrot M, Varga J, Mathews WB, Ravert HT, Dannals RF, Wand G (2004) Positron emission tomography imaging of the serotonin transporter in subjects with a history of alcoholism. Biol Psychiatry 55:766-771
104. Brown AK, George DT, Fujita M, Liow JS, Ichise M, Hibbeln J, Ghose S, Sangare J, Hommer D, Innis RB (2007) PET [11C] DASB imaging of serotonin transporters in patients with alcoholism. Alcohol Clin Exp Res 31:28-32
105. Hu J, Henry S, Gallezot JD, Ropchan J, Neumaier JF, Potenza MN, Sinha R, Krystal JH, Huang Y, Ding YS, Carson RE, Neumeister A (2010) Serotonin 1B receptor imaging in alcohol dependence. Biol Psychiatry 67:800-803
106. Nishikawa M, Diksic M, Sakai Y, Kumano H, Charney D, Palacios-Boix J, Negrete J, Gill K (2009) Alterations in brain serotonin synthesis in male alcoholics measured using positron emission tomography. Alcohol Clin Exp Res 33:233-239
107. Zubieta J, Greenwald MK, Lombardi U, Woods JH, Kilbourn MR, Jewett DM, Koeppe RA, Schuster CR, Johanson CE (2000) Buprenorphine-induced changes in mu-opioid receptor availability in male heroin-dependent volunteers: a preliminary study. Neuropsychopharmacology 23:326-334
108. Kling MA, Carson RE, Borg L, Zametkin A, Matochik JA, Schluger J, Herscovitch P, Rice KC, Ho A, Eckelman WC, Kreek MJ (2000) Opioid receptor imaging with positron emission tomography and [(18)F]cyclofoxy in long-term, methadone-treated former heroin addicts. J Pharmacol Exp Ther 295:1070-1076
109. Greenwald MK, Johanson CE, Moody DE, Woods JH, Kilbourn MR, Koeppe RA, Schuster CR, Zubieta JK (2003) Effects of buprenorphine maintenance dose on mu-opioid receptor availability, plasma concentrations, and antagonist blockade in heroin-dependent volunteers. Neuropsychopharmacology 28:2000-2009
110. Wang GJ, Volkow ND, Fowler JS, Logan J, Abumrad NN, Hitzemann RJ, Pappas NS, Pascani K (1997) Dopamine D2 receptor availability in opiate-dependent subjects before and after naloxone-precipitated withdrawal. Neuropsychopharmacology 16:174-182
111. Zijlstra F, Booij J, van den Brink W, Franken IH (2008) Striatal dopamine D2 receptor binding and dopamine release during cueelicited craving in recently abstinent opiatedependent males. Eur Neuropsychopharmacol 18:262-270
112. Shi J, Zhao LY, Copersino ML, Fang YX, Chen Y, Tian J, Deng Y, Shuai Y, Jin J, Lu L (2008) PET imaging of dopamine transporter and drug craving during methadone maintenance treatment and after prolonged abstinence in heroin users. Eur J Pharmacol 579:160-166
113. Reneman L, Booij J, de Bruin K, Reitsma JB, de Wolff FA, Gunning WB, den Heeten GJ, van den Brink W (2001) Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons. Lancet 358:1864-1869
114. Semple DM, Ebmeier KP, Glabus MF, O'Carroll RE, Johnstone EC (1999) Reduced in vivo binding to the serotonin transporter in the cerebral cortex of MDMA ('ecstasy') users. Br J Psychiatry 175:63-69
115. Buchert R, Thomasius R, Wilke F, Petersen K, Nebeling B, Obrocki J, Schulze O, Schmidt U, Clausen M (2004) A voxel-based PET investigation of the long-term effects of Ecstasy consumption on brain serotonin transporters. Am J Psychiatry 161:1181-1189
116. McCann UD, Szabo Z, Scheffel U, Dannals RF, Ricaurte GA (1998) Positron emission tomographic evidence of toxic effect of MDMA (Ecstasy) on brain serotonin neurons in human beings. Lancet 352:1433-1437
117. McCann UD, Szabo Z, Seckin E, Rosenblatt P, Mathews WB, Ravert HT, Dannals RF, Ricaurte GA (2005) Quantitative PET studies of the serotonin transporter in MDMA users and controls using [11C]McN5652 and [11C] DASB. Neuropsychopharmacology 30:1741-1750
118. Kish SJ, Lerch J, Furukawa Y, Tong J, McCluskey T, Wilkins D, Houle S, Meyer J, Mundo E, Wilson AA, Rusjan PM, Saint-Cyr JA, Guttman M, Collins DL, Shapiro C, Warsh JJ, Boileau I (2010) Decreased cerebral cortical serotonin transporter binding in ecstasy users: a positron emission tomography/[( 11)C]DASB and structural brain imaging study. Brain 133:1779-1797
119. Kuikka JT, Repo E, Bergstrom KA, Tupala E, Tiihonen J (2000) Specific binding and laterality of human extrastriatal dopamine D2/D3 receptors in late onset type 1 alcoholic patients. Neurosci Lett 292:57-59