Development and Pilot Validation of Computer-Assisted Self-Infusion of Ethanol (CASE): A New Method to Study Alcohol Self-Administration in Humans
Background: Human alcohol self‐administration studies employing oral intake are subject to high variability of the resulting blood alcohol concentrations because of idiosyncrasies of gastrointestinal absorption kinetics among subjects. We sought to improve the subjects’ opportunity to control their...
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| Published in | Alcoholism, clinical and experimental research Vol. 32; no. 7; pp. 1321 - 1328 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Oxford, UK
Blackwell Publishing Ltd
01.07.2008
Lippincott Williams & Wilkins |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0145-6008 1530-0277 1530-0277 |
| DOI | 10.1111/j.1530-0277.2008.00700.x |
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| Abstract | Background: Human alcohol self‐administration studies employing oral intake are subject to high variability of the resulting blood alcohol concentrations because of idiosyncrasies of gastrointestinal absorption kinetics among subjects. We sought to improve the subjects’ opportunity to control their brain alcohol exposure by computer‐assisted i.v. self‐administration.
Methods: Instead of drinking, subjects could request increments of their arterial blood alcohol concentration (aBAC) of precisely 7.5 mg% at any time they wanted by pressing a button, provided their aBAC would not exceed 100 mg%. The latency between pushing the button and reaching the new aBAC peak was preset to be 2.5 minutes on the first day and was randomly changed to 1.5 or 3.5 minutes on days 2 and 3 in a crossover design. The necessary rate and amount of alcohol infusion was calculated by the software about once every second. Nine healthy social drinkers (4 females/5 males; mean age 25.0 ± 4.0 year) participated in 3 sessions each. Outcome measures were mean and maximum observed aBAC, and the number of alcohol requests.
Results: Maximum aBAC was 76.5 ± 26.3 mg% on average over all experiments. When grouping days 2 and 3 according to latency (1.5 vs. 3.5 minutes), maximum aBAC and the number of requests in the session were significantly higher with the faster rise and all 3 outcome measures were significantly correlated between days. No such correlations were found between the first and either of the following days.
Conclusions: These data suggest that CASE is practical and safe, and results in considerable alcohol exposure that can be manipulated with parameters chosen for the incremental exposure. Following 1 practice day, test–retest stability was good, suggesting a potential for use in scientific studies. |
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| AbstractList | Human alcohol self-administration studies employing oral intake are subject to high variability of the resulting blood alcohol concentrations because of idiosyncrasies of gastrointestinal absorption kinetics among subjects. We sought to improve the subjects' opportunity to control their brain alcohol exposure by computer-assisted i.v. self-administration.
Instead of drinking, subjects could request increments of their arterial blood alcohol concentration (aBAC) of precisely 7.5 mg% at any time they wanted by pressing a button, provided their aBAC would not exceed 100 mg%. The latency between pushing the button and reaching the new aBAC peak was preset to be 2.5 minutes on the first day and was randomly changed to 1.5 or 3.5 minutes on days 2 and 3 in a crossover design. The necessary rate and amount of alcohol infusion was calculated by the software about once every second. Nine healthy social drinkers (4 females/5 males; mean age 25.0 +/- 4.0 year) participated in 3 sessions each. Outcome measures were mean and maximum observed aBAC, and the number of alcohol requests.
Maximum aBAC was 76.5 +/- 26.3 mg% on average over all experiments. When grouping days 2 and 3 according to latency (1.5 vs. 3.5 minutes), maximum aBAC and the number of requests in the session were significantly higher with the faster rise and all 3 outcome measures were significantly correlated between days. No such correlations were found between the first and either of the following days.
These data suggest that CASE is practical and safe, and results in considerable alcohol exposure that can be manipulated with parameters chosen for the incremental exposure. Following 1 practice day, test-retest stability was good, suggesting a potential for use in scientific studies. Background: Human alcohol self‐administration studies employing oral intake are subject to high variability of the resulting blood alcohol concentrations because of idiosyncrasies of gastrointestinal absorption kinetics among subjects. We sought to improve the subjects’ opportunity to control their brain alcohol exposure by computer‐assisted i.v. self‐administration. Methods: Instead of drinking, subjects could request increments of their arterial blood alcohol concentration (aBAC) of precisely 7.5 mg% at any time they wanted by pressing a button, provided their aBAC would not exceed 100 mg%. The latency between pushing the button and reaching the new aBAC peak was preset to be 2.5 minutes on the first day and was randomly changed to 1.5 or 3.5 minutes on days 2 and 3 in a crossover design. The necessary rate and amount of alcohol infusion was calculated by the software about once every second. Nine healthy social drinkers (4 females/5 males; mean age 25.0 ± 4.0 year) participated in 3 sessions each. Outcome measures were mean and maximum observed aBAC, and the number of alcohol requests. Results: Maximum aBAC was 76.5 ± 26.3 mg% on average over all experiments. When grouping days 2 and 3 according to latency (1.5 vs. 3.5 minutes), maximum aBAC and the number of requests in the session were significantly higher with the faster rise and all 3 outcome measures were significantly correlated between days. No such correlations were found between the first and either of the following days. Conclusions: These data suggest that CASE is practical and safe, and results in considerable alcohol exposure that can be manipulated with parameters chosen for the incremental exposure. Following 1 practice day, test–retest stability was good, suggesting a potential for use in scientific studies. Human alcohol self-administration studies employing oral intake are subject to high variability of the resulting blood alcohol concentrations because of idiosyncrasies of gastrointestinal absorption kinetics among subjects. We sought to improve the subjects' opportunity to control their brain alcohol exposure by computer-assisted i.v. self-administration.BACKGROUNDHuman alcohol self-administration studies employing oral intake are subject to high variability of the resulting blood alcohol concentrations because of idiosyncrasies of gastrointestinal absorption kinetics among subjects. We sought to improve the subjects' opportunity to control their brain alcohol exposure by computer-assisted i.v. self-administration.Instead of drinking, subjects could request increments of their arterial blood alcohol concentration (aBAC) of precisely 7.5 mg% at any time they wanted by pressing a button, provided their aBAC would not exceed 100 mg%. The latency between pushing the button and reaching the new aBAC peak was preset to be 2.5 minutes on the first day and was randomly changed to 1.5 or 3.5 minutes on days 2 and 3 in a crossover design. The necessary rate and amount of alcohol infusion was calculated by the software about once every second. Nine healthy social drinkers (4 females/5 males; mean age 25.0 +/- 4.0 year) participated in 3 sessions each. Outcome measures were mean and maximum observed aBAC, and the number of alcohol requests.METHODSInstead of drinking, subjects could request increments of their arterial blood alcohol concentration (aBAC) of precisely 7.5 mg% at any time they wanted by pressing a button, provided their aBAC would not exceed 100 mg%. The latency between pushing the button and reaching the new aBAC peak was preset to be 2.5 minutes on the first day and was randomly changed to 1.5 or 3.5 minutes on days 2 and 3 in a crossover design. The necessary rate and amount of alcohol infusion was calculated by the software about once every second. Nine healthy social drinkers (4 females/5 males; mean age 25.0 +/- 4.0 year) participated in 3 sessions each. Outcome measures were mean and maximum observed aBAC, and the number of alcohol requests.Maximum aBAC was 76.5 +/- 26.3 mg% on average over all experiments. When grouping days 2 and 3 according to latency (1.5 vs. 3.5 minutes), maximum aBAC and the number of requests in the session were significantly higher with the faster rise and all 3 outcome measures were significantly correlated between days. No such correlations were found between the first and either of the following days.RESULTSMaximum aBAC was 76.5 +/- 26.3 mg% on average over all experiments. When grouping days 2 and 3 according to latency (1.5 vs. 3.5 minutes), maximum aBAC and the number of requests in the session were significantly higher with the faster rise and all 3 outcome measures were significantly correlated between days. No such correlations were found between the first and either of the following days.These data suggest that CASE is practical and safe, and results in considerable alcohol exposure that can be manipulated with parameters chosen for the incremental exposure. Following 1 practice day, test-retest stability was good, suggesting a potential for use in scientific studies.CONCLUSIONSThese data suggest that CASE is practical and safe, and results in considerable alcohol exposure that can be manipulated with parameters chosen for the incremental exposure. Following 1 practice day, test-retest stability was good, suggesting a potential for use in scientific studies. Background: Human alcohol self‐administration studies employing oral intake are subject to high variability of the resulting blood alcohol concentrations because of idiosyncrasies of gastrointestinal absorption kinetics among subjects. We sought to improve the subjects’ opportunity to control their brain alcohol exposure by computer‐assisted i.v. self‐administration. Methods: Instead of drinking, subjects could request increments of their arterial blood alcohol concentration (aBAC) of precisely 7.5 mg% at any time they wanted by pressing a button, provided their aBAC would not exceed 100 mg%. The latency between pushing the button and reaching the new aBAC peak was preset to be 2.5 minutes on the first day and was randomly changed to 1.5 or 3.5 minutes on days 2 and 3 in a crossover design. The necessary rate and amount of alcohol infusion was calculated by the software about once every second. Nine healthy social drinkers (4 females/5 males; mean age 25.0 ± 4.0 year) participated in 3 sessions each. Outcome measures were mean and maximum observed aBAC, and the number of alcohol requests. Results: Maximum aBAC was 76.5 ± 26.3 mg% on average over all experiments. When grouping days 2 and 3 according to latency (1.5 vs. 3.5 minutes), maximum aBAC and the number of requests in the session were significantly higher with the faster rise and all 3 outcome measures were significantly correlated between days. No such correlations were found between the first and either of the following days. Conclusions: These data suggest that CASE is practical and safe, and results in considerable alcohol exposure that can be manipulated with parameters chosen for the incremental exposure. Following 1 practice day, test–retest stability was good, suggesting a potential for use in scientific studies. |
| Author | Mick, Inge Plawecki, Martin H. Vitvitskyi, Victor Mann, Karl F. O'Connor, Sean Zimmermann, Ulrich S. |
| AuthorAffiliation | 2 Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 4 Current affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany 3 R.L. Roudebush VA Medical Center, Indianapolis, IN 1 Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Mannheim, Germany |
| AuthorAffiliation_xml | – name: 4 Current affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany – name: 2 Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN – name: 1 Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Mannheim, Germany – name: 3 R.L. Roudebush VA Medical Center, Indianapolis, IN |
| Author_xml | – sequence: 1 givenname: Ulrich S. surname: Zimmermann fullname: Zimmermann, Ulrich S. organization: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health (USZ, IM, KFM), Mannheim, Germany; Department of Psychiatry, Indiana University School of Medicine (VV, MHP, SOC), Indianapolis, Indiana; R.L. Roudebush VA Medical Center (SOC), Indianapolis, Indiana – sequence: 2 givenname: Inge surname: Mick fullname: Mick, Inge organization: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health (USZ, IM, KFM), Mannheim, Germany; Department of Psychiatry, Indiana University School of Medicine (VV, MHP, SOC), Indianapolis, Indiana; R.L. Roudebush VA Medical Center (SOC), Indianapolis, Indiana – sequence: 3 givenname: Victor surname: Vitvitskyi fullname: Vitvitskyi, Victor organization: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health (USZ, IM, KFM), Mannheim, Germany; Department of Psychiatry, Indiana University School of Medicine (VV, MHP, SOC), Indianapolis, Indiana; R.L. Roudebush VA Medical Center (SOC), Indianapolis, Indiana – sequence: 4 givenname: Martin H. surname: Plawecki fullname: Plawecki, Martin H. organization: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health (USZ, IM, KFM), Mannheim, Germany; Department of Psychiatry, Indiana University School of Medicine (VV, MHP, SOC), Indianapolis, Indiana; R.L. Roudebush VA Medical Center (SOC), Indianapolis, Indiana – sequence: 5 givenname: Karl F. surname: Mann fullname: Mann, Karl F. organization: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health (USZ, IM, KFM), Mannheim, Germany; Department of Psychiatry, Indiana University School of Medicine (VV, MHP, SOC), Indianapolis, Indiana; R.L. Roudebush VA Medical Center (SOC), Indianapolis, Indiana – sequence: 6 givenname: Sean surname: O'Connor fullname: O'Connor, Sean organization: Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health (USZ, IM, KFM), Mannheim, Germany; Department of Psychiatry, Indiana University School of Medicine (VV, MHP, SOC), Indianapolis, Indiana; R.L. Roudebush VA Medical Center (SOC), Indianapolis, Indiana |
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| Copyright | Copyright © 2008 by the Research Society on Alcoholism 2008 INIST-CNRS |
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| Keywords | Human Validation Alcoholic beverage Infusion Ethanol Perfusion Development Self administration Method Self Computer aid |
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| Notes | ark:/67375/WNG-4S43G2QD-S istex:70C447171139FA043C1532D2EFF0E3B8844D7E4C ArticleID:ACER700 Present address: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus (USZ, IM), Technische Universität Dresden, Dresden, Germany. This project was supported by Grant No. P60 AA007611‐20 from the National Institute on Alcohol Abuse and Alcoholism. The contents of this report are solely the responsibility of the authors and do not necessarily represent the official view of the National Institute on Alcohol Abuse and Alcoholism or NIH. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 |
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| References_xml | – reference: Donny EC, Bigelow GE, Walsh SL (2006) Comparing the physiological and subjective effects of self-administered vs yoked cocaine in humans. Psychopharmacology (Berl) 186:544-552. – reference: Sofuoglu M, Yoo S, Hill KP, Mooney M (2008) Self-administration of intravenous nicotine in male and female cigarette smokers. Neuropsychopharmacology 33:715-720. – reference: Acheson A, Mahler SV, Chi H, De Wit H (2006) Differential effects of nicotine on alcohol consumption in men and women. Psychopharmacology (Berl) 186:54-63. – reference: Krishnan-Sarin S, Krystal JH, Shi J, Pittman B, O'Malley SS (2007) Family history of alcoholism influences Naltrexone-induced reduction in alcohol drinking. Biol Psychiatry 62:694-697. – reference: Lachner G, Wittchen HU, Perkonigg A, Holly A, Schuster P, Wunderlich U, Turk D, Garczynski E, Pfister H (1998) Structure, content and reliability of the Munich-Composite International Diagnostic Interview (M-CIDI) substance use sections. Eur Addict Res 4:28-41. – reference: Plawecki MH, Han JJ, Doerschuk PC, Ramchandani VA, O'Connor S 2008 A physiologically-based pharmacokinetic (PBPK) model for alcohol: mathematical foundations. IEEE Trans Biomed Eng. In press. – reference: De Wit H, McCracken SG (1990) Ethanol self-administration in males with and without an alcoholic first-degree relative. Alcohol Clin Exp Res 14:63-70. – reference: Drobes DJ, Anton R (2000) Drinking in alcoholics following an alcohol challenge research protocol. J Stud Alcohol 61:220-224. – reference: Drobes DJ, Anton RF, Thomas SE, Voronin K (2003) A clinical laboratory paradigm for evaluating medication effects on alcohol consumption: naltrexone and nalmefene. Neuropsychopharmacology 28:755-764. – reference: Plawecki MH, DeCarlo RA, Ramchandani VA, O'Connor S (2007) Improved transformation of morphometric measurements for a priori parameter estimation in a physiologically-based pharmacokinetic model of ethanol. Biomedical Signal Processing and Control 2:97-110. – reference: O'Connor S, Morzorati S, Zimmermann US, Flury L (2007) Ascending or descending BrAC; who knows? Alcohol Clin Exp Res 31:252A. – reference: Lindberg L, Brauer S, Wollmer P, Goldberg L, Jones AW, Olsson SG (2007) Breath alcohol concentration determined with a new analyzer using free exhalation predicts almost precisely the arterial blood alcohol concentration. Forensic Sci Int 168:200-207. – reference: Martin CS, Earleywine M, Musty RE, Perrine RE, Swift RM (1993) Development and validation of the biphasic alcohol effects scale. Alcohol Clin Exp Res 17:140-146. – reference: O'Malley SS, Krishnan-Sarin S, Farren C, Sinha R, Kreek J (2002) Naltrexone decreases craving and alcohol self-administration in alcohol-dependent subjects and activates the hypothalamo-pituitary-adrenocortical axis. Psychopharmacology (Berl) 160:19-29. – reference: Jones AW, Norberg A, Hahn RG (1997) Concentration-time profiles of ethanol in arterial and venous blood and end-expired breath during and after intravenous infusion. J Forensic Sci 42:1088-1094. – reference: O'Connor S, Ramchandani VA, Li TK (2000) PBPK modeling as a basis for achieving a steady BrAC of 60+/−5 mg% within ten minutes. Alcohol Clin Exp Res 24:426-427. – reference: 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. – reference: De Wit H, Soderpalm AH, Nikolayev L, Young E (2003) Effects of acute social stress on alcohol consumption in healthy subjects. Alcohol Clin Exp Res 27:1270-1277. – reference: Young EM, Mahler S, Chi H, De Wit H (2005) Mecamylamine and ethanol preference in healthy volunteers. Alcohol Clin Exp Res 29:58-65. – reference: Pratt WM, Davidson D (2005) Does participation in an alcohol administration study increase risk for excessive drinking? Alcohol 37:135-141. – reference: Ramchandani VA, O'Connor S, Neumark YD, Zimmermann US, Morzorati S, De Wit H (2006) The alcohol clamp: applications, challenges and new directions - an RSA 2004 symposium summary. Alcohol Clin Exp Res 30:155-164. – reference: Petrakis IL, Buonopane A, O'Malley S, Cermik O, Trevisan L, Boutros NN, Limoncelli D, Krystal JH (2002) The effect of tryptophan depletion on alcohol self-administration in non-treatment-seeking alcoholic individuals. Alcohol Clin Exp Res 26:969-975. – volume: 31 start-page: 252A year: 2007 article-title: Ascending or descending BrAC; who knows? publication-title: Alcohol Clin Exp Res – volume: 37 start-page: 135 year: 2005 end-page: 141 article-title: Does participation in an alcohol administration study increase risk for excessive drinking? publication-title: Alcohol – volume: 30 start-page: 155 year: 2006 end-page: 164 article-title: The alcohol clamp: applications, challenges and new directions – an RSA 2004 symposium summary publication-title: Alcohol Clin Exp Res – volume: 14 start-page: 63 year: 1990 end-page: 70 article-title: Ethanol self‐administration in males with and without an alcoholic first‐degree relative publication-title: Alcohol Clin Exp Res – volume: 186 start-page: 54 year: 2006 end-page: 63 article-title: Differential effects of nicotine on alcohol consumption in men and women publication-title: Psychopharmacology (Berl) – volume: 61 start-page: 220 year: 2000 end-page: 224 article-title: Drinking in alcoholics following an alcohol challenge research protocol publication-title: J Stud Alcohol – volume: 17 start-page: 140 year: 1993 end-page: 146 article-title: Development and validation of the biphasic alcohol effects scale publication-title: Alcohol Clin Exp Res – volume: 160 start-page: 19 year: 2002 end-page: 29 article-title: Naltrexone decreases craving and alcohol self‐administration in alcohol‐dependent subjects and activates the hypothalamo‐pituitary‐adrenocortical axis publication-title: Psychopharmacology (Berl) – volume: 4 start-page: 28 year: 1998 end-page: 41 article-title: Structure, content and reliability of the Munich‐Composite International Diagnostic Interview (M‐CIDI) substance use sections publication-title: Eur Addict Res – volume: 22 start-page: 202 year: 1998 end-page: 210 article-title: Clamping breath alcohol concentration reduces experimental variance: application to the study of acute tolerance to alcohol and alcohol elimination rate publication-title: Alcohol Clin Exp Res – year: 2008 article-title: A physiologically‐based pharmacokinetic (PBPK) model for alcohol: mathematical foundations publication-title: IEEE Trans Biomed Eng – volume: 28 start-page: 755 year: 2003 end-page: 764 article-title: A clinical laboratory paradigm for evaluating medication effects on alcohol consumption: naltrexone and nalmefene publication-title: Neuropsychopharmacology – volume: 29 start-page: 58 year: 2005 end-page: 65 article-title: Mecamylamine and ethanol preference in healthy volunteers publication-title: Alcohol Clin Exp Res – volume: 168 start-page: 200 year: 2007 end-page: 207 article-title: Breath alcohol concentration determined with a new analyzer using free exhalation predicts almost precisely the arterial blood alcohol concentration publication-title: Forensic Sci Int – volume: 42 start-page: 1088 year: 1997 end-page: 1094 article-title: Concentration‐time profiles of ethanol in arterial and venous blood and end‐expired breath during and after intravenous infusion publication-title: J Forensic Sci – volume: 62 start-page: 694 year: 2007 end-page: 697 article-title: Family history of alcoholism influences Naltrexone‐induced reduction in alcohol drinking publication-title: Biol Psychiatry – volume: 33 start-page: 715 year: 2008 end-page: 720 article-title: Self‐administration of intravenous nicotine in male and female cigarette smokers publication-title: Neuropsychopharmacology – volume: 24 start-page: 426 year: 2000 end-page: 427 article-title: PBPK modeling as a basis for achieving a steady BrAC of 60+/−5 mg% within ten minutes publication-title: Alcohol Clin Exp Res – volume: 186 start-page: 544 year: 2006 end-page: 552 article-title: Comparing the physiological and subjective effects of self‐administered vs yoked cocaine in humans publication-title: Psychopharmacology (Berl) – volume: 26 start-page: 969 year: 2002 end-page: 975 article-title: The effect of tryptophan depletion on alcohol self‐administration in non‐treatment‐seeking alcoholic individuals publication-title: Alcohol Clin Exp Res – volume: 27 start-page: 1270 year: 2003 end-page: 1277 article-title: Effects of acute social stress on alcohol consumption in healthy subjects publication-title: Alcohol Clin Exp Res – volume: 2 start-page: 97 year: 2007 end-page: 110 article-title: Improved transformation of morphometric measurements for a priori parameter estimation in a physiologically‐based pharmacokinetic model of ethanol publication-title: Biomedical Signal Processing and Control – ident: e_1_2_5_15_1 doi: 10.1111/j.1530-0277.2002.tb02629.x – ident: e_1_2_5_14_1 doi: 10.1007/s002130100919 – ident: e_1_2_5_5_1 doi: 10.1038/sj.npp.1300101 – ident: e_1_2_5_23_1 doi: 10.1097/01.ALC.0000150007.34702.16 – volume: 24 start-page: 426 year: 2000 ident: e_1_2_5_13_1 article-title: PBPK modeling as a basis for achieving a steady BrAC of 60+/−5 mg% within ten minutes publication-title: Alcohol Clin Exp Res 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| Snippet | Background: Human alcohol self‐administration studies employing oral intake are subject to high variability of the resulting blood alcohol concentrations... Background: Human alcohol self‐administration studies employing oral intake are subject to high variability of the resulting blood alcohol concentrations... Human alcohol self-administration studies employing oral intake are subject to high variability of the resulting blood alcohol concentrations because of... |
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| SubjectTerms | Adult Alcoholism and acute alcohol poisoning Biological and medical sciences Central Nervous System Depressants - administration & dosage Central Nervous System Depressants - blood Ethanol Ethanol - administration & dosage Ethanol - blood Female Humans Infusion Infusions, Intravenous - methods Male Medical sciences Pilot Projects Self Administration Self Administration - methods Toxicology |
| Title | Development and Pilot Validation of Computer-Assisted Self-Infusion of Ethanol (CASE): A New Method to Study Alcohol Self-Administration in Humans |
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