Abstract
Rationale
Acute alcohol effects may differ in social drinkers with a positive family history of alcohol use disorders (FHP) compared to FH negative (FHN) controls.
Objectives
To investigate whether FHP subjects prefer higher levels of brain alcohol exposure than do FHN controls.
Materials and methods
Twenty-two young healthy nondependent social drinkers participated in two identical sessions of computer-assisted self-infusion of ethanol (CASE); the first for practicing the procedures, the second to test hypotheses. All 12 FHP (four women) and ten FHN (three women) participants received a priming exposure, increasing arterial blood alcohol concentration (aBAC) to 30 mg% at 10 min and decreasing it to 15 mg% at 25 min. A 2-h self-administration period followed, during which only the subjects could increase their aBAC by pressing a button connected to a computer controlling the infusion pump. Infusion rate profiles were calculated instantaneously to increase aBAC by precisely 7.5 mg% within 2.5 min after each button press, followed by a steady descent. Subjects were instructed to produce the same alcohol effects as they would do at a weekend party.
Results
The mean and maximum aBAC during the self-administration period and the number of alcohol requests (NOAR) were significantly higher in the FHP vs. FHN participants.
Conclusions
This is the first laboratory experiment demonstrating higher alcohol self-administration in FHP compared to FHN subjects. A practice session increases the sensitivity of CASE experiments for detection of subtle differences in human alcohol self-administration.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Acheson A, Mahler SV, Chi H, de WH (2006) Differential effects of nicotine on alcohol consumption in men and women. Psychopharmacology (Berl) 186:54–63
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
Crabbe JC, Phillips TJ, Harris RA, Arends MA, Koob GF (2006) Alcohol-related genes: contributions from studies with genetically engineered mice. Addict Biol 11:195–269
Davidson D, Camara P, Swift R (1997) Behavioral effects and pharmacokinetics of low-dose intravenous alcohol in humans. Alcohol Clin Exp Res 21:1294–1299
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
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
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
Han JJ, Plawecki MH, Doerschuk PC, Ramchandani VA, O’Connor S (2006) Ordinary differential equation models for ethanol pharmacokinetic based on anatomy and physiology. Conf Proc IEEE Eng Med Biol Soc 1:5033–5036
Heath AC, Bucholz K, Madden PA, Dinwiddie SH, Slutske WS, Bierut L, Statham DJ, Dunne MP, Whitfield JB, Martin NG (1997) Genetic and environmental contributions to alcohol dependence risk in a national twin sample: consistency of findings in women and men. Psychol Med 27:1381–1396
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
Laucht M, Esser G, Baving L, Gerhold M, Hoesch I, Ihle W, Steigleider P, Stock B, Stoehr RM, Weindrich D, Schmidt MH (2000) Behavioral sequelae of perinatal insults and early family adversity at 8 years of age. J Am Acad Child Adolesc Psych 39:1229–1237
Martin CS, Earleywine M, Musty RE, Perrine RE, Swift RM (1993) Development and validation of the biphasic alcohol effects scale. Alcoholism: Clinical & Experimental Research 17:140–146
Newlin DB, Thomson JB (1990) Alcohol challenge with sons of alcoholics: a critical review and analysis. Psychol Bull 180:383–402
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
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
Plawecki MH, DeCarlo RA, Ramchandani VA, O’Connor S (2004) Estimation of ethanol infusion profile to produce specified BrAC time course using physiologically-based pharmacokinetic (PBPK) models. Conf Proc IEEE Eng Med Biol Soc 1:778–781
Prescott CA, Kendler KS (1999) Genetic and environmental contributions to alcohol abuse and dependence in a population-based sample of male twins. Am J Psychiatr 156:34–40
Ramchandani VA, Bolane J, Li TK, O’Connor S (1999) A physiologically-based pharmacokinetic (PBPK) model for alcohol facilitates rapid BrAC clamping. Alcoholism: Clinical & Experimental Research 23:617–623
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
Schuckit MA (1994) Low level of response to alcohol as a predictor of future alcoholism. Am J Psychiatry 151:184–189
Schuckit MA, Gold EO (1988) A simultaneous evaluation of multiple markers of ethanol/placebo challenges in sons of alcoholics and controls. Arch Gen Psychiatry 45:211–216
Schuckit MA, Risch SC, Gold E (1988) Alcohol consumption, ACTH level, and family history of alcoholism. Am J Psychiatry 145:1391–1395
Sigvardsson S, Bohman M, Cloninger CR (1996) Replication of the Stockholm adoption study of alcoholism. Arch Gen Psychiatry 53:681–687
Sobell LC, Brown J, Leo GI, Sobell MB (1996) The reliability of the Alcohol Timeline Followback when administered by telephone and by computer. Drug Alcohol Depend 42:49–54
Wittchen HU, Semler G (1990) Composite international interview (CIDI, Version 1.0). Beltz, Weinheim
Wittchen HU, Zaudig M, Fydrich T (1997) Strukturiertes klinisches Interview für DSM-IV Achse I und II- SKID. Hogrefe, Göttingen
World Health Organization (1991) Tenth Revision of the International Classification of Diseases, Chapter V (F): Mental and Behavioral Disorders. Clinical Descriptions and Diagnostic Guidelines
Young EM, Mahler S, Chi H, de Wit H (2005) Mecamylamine and ethanol preference in healthy volunteers. Alcohol Clin Exp Res 29:58–65
Zimmermann US, Mick I, Vitvitskyi V, Plawecki MH, Mann KF, O’Connor S (2008) Development and pilot validation of computer-assisted self-infusion of ethanol (CASE): a new method to study alcohol self-administration in humans. Alcohol Clin Exp Res 32:1321–1328
Acknowledgements
We gratefully acknowledge help with conducting the experiments and with data management by Anna Kornadt, and help with recruitment of the participants by Sibylle Heinzel and Elisabeth Reichert.
This experiment fully complies with the current laws of the country in which it was performed; i.e., the Federal Republic of Germany.
The authors declare that they do not have a financial relationship with the organization that sponsored this research, i.e., the NIAAA, other than receiving grants. They further declare that there is no other conflict of interest regarding publication of these data.
The authors have full control of all primary data and agree to allow the journal to review these data, if requested.
This study was supported by Grant No. P60 AA007611-20 from the National Institute on Alcohol Abuse and Alcoholism.
Furthermore, the ongoing longitudinal survey of the study sample was supported by grants from the Deutsche Forschungsgemeinschaft (DFG), and from the German Bundesministerium für Bildung und Forschung (BMBF) supporting the research programs “Baden-Wuerttemberg Consortium for Addiction Research” and the German National Genome Research Network.
Author information
Authors and Affiliations
Corresponding authors
Additional information
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.
Rights and permissions
About this article
Cite this article
Zimmermann, U.S., Mick, I., Laucht, M. et al. Offspring of parents with an alcohol use disorder prefer higher levels of brain alcohol exposure in experiments involving computer-assisted self-infusion of ethanol (CASE). Psychopharmacology 202, 689–697 (2009). https://doi.org/10.1007/s00213-008-1349-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-008-1349-7