Abstract
Rationale and objective
Poor inhibitory control is a well-established risk factor for alcohol use disorder (AUD). Similarly, greater sensitivity to the stimulant effects and less sensitivity to the sedative effects of alcohol are also strongly linked to risk for AUD. Traditionally, these two risk factors have been considered to be orthogonal, and thus they have been studied independently. However, recent evidence from animal and human studies suggests that they may be related. The current study examined the relationship between inhibitory control and subjective responses to alcohol in a sample of healthy young adults.
Methods
Moderate social drinkers (N = 69) first completed the stop signal task to assess inhibitory control. They then participated in four sessions in which they received an oral dose of ethanol (0.8 g/kg) or placebo in alternating order, providing self-report measures of stimulation and sedation on the Biphasic Alcohol Effects Scale (BAES) at regular intervals.
Results
Linear mixed effects models showed that poor inhibitory control was associated with greater stimulation and less sedation following alcohol compared with placebo.
Conclusion
These findings provide the first direct evidence that individuals with poor inhibitory control experience greater sensitivity to the rewarding, stimulant effects of alcohol, and less sensitivity to the negative, sedative effects. These findings suggest that inhibition and subjective response to alcohol are not independent risk factors, and that together they constitute a heightened profile of risk for AUD.
Similar content being viewed by others
References
Beckwith SW, Czachowski CL (2016) Alcohol-preferring P rats exhibit elevated motor impulsivity concomitant with operant responding and self-administration of alcohol. Alcohol Clin Exp Res 40:1100–1110
Belin D, Mar AC, Dalley JW, Robbins TW, Everitt BJ (2008) High impulsivity predicts the switch to compulsive cocaine-taking. Science 320:1352–1355
Berey BL, Leeman RF, Pittman B, O'Malley SS (2017) Relationships of impulsivity and subjective response to alcohol use and related problems. J Stud Alcohol Drugs 78:835–843
Berey BL, Leeman RF, Chavarria J, King AC (2019) Relationships between generalized impulsivity and subjective stimulant and sedative responses following alcohol administration. Psychol Addict Behav
Bowers BJ, Wehner JM (2001) Ethanol consumption and behavioral impulsivity are increased in protein kinase Cgamma null mutant mice. J Neurosci 21:RC180
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
de Wit H (2009) Impulsivity as a determinant and consequence of drug use: a review of underlying processes. Addict Biol 14:22–31
Fernie G, Peeters M, Gullo MJ, Christiansen P, Cole JC, Sumnall H, Field M (2013) Multiple behavioural impulsivity tasks predict prospective alcohol involvement in adolescents. Addiction 108:1916–1923
Fillmore MT (2001) Cognitive preoccupation with alcohol and binge drinking in college students: alcohol-induced priming of the motivation to drink. Psychol Addict Behav 15:325–332
Fillmore MT, Weafer J (2013) Behavioral inhibition and addiction. In The Wiley-Blackwell Handbook of Addiction Psychopharmacology, Mackillop J and de Wit H (Eds) pp 135-164
Furr CDM, Delva J, Anthony JC (2000) The suspected association between methamphetamine (‘ice’) smoking and frequent episodes of alcohol intoxication: data from the 1993 National Household Survey on drug abuse. Drug Alcohol Depend 59:89–93
Ghahremani DG, Lee B, Robertson CL, Tabibnia G, Morgan AT, De Shetler N, Brown AK, Monterosso JR, Aron AR, Mandelkern MA, Poldrack RA, London ED (2012) Striatal dopamine D(2)/D(3) receptors mediate response inhibition and related activity in frontostriatal neural circuitry in humans. J Neurosci 32:7316–7324
Hedeker D, Gibbons RD (2006) Longitudinal Data Analysis. Wiley, Hoboken
Heil SH, Badger GJ, Higgins ST (2001) Alcohol dependence among cocaine-dependent outpatients: demographics, drug use, treatment outcome and other characteristics. J Stud Alcohol 62:14–22
Hendershot CS, Wardell JD, Markovich MSD SNM, Claus ED, Ramchandani VA (2015) Application of an alcohol clamp paradigm to examine inhibitory control, subjective responses and acute tolerance in late adolescence. Exp Clin Psychopharmacol 23:147–158
Jentsch JD, Pennington ZT (2014) Reward, interrupted: inhibitory control and its relevance to addictions. Neuropharmacology 76:479–486
King AC, Houle T, de Wit H, Holdstock L, Schuster A (2002) Biphasic alcohol response differs in heavy versus light drinkers. Alcohol Clin Exp Res 26:827–835
King AC, de Wit H, McNamara PJ, Cao DC (2011) Rewarding, stimulant, and sedative alcohol responses and relationship to future binge drinking. Arch Gen Psychiatry 68:389–399
King AC, McNamara PJ, Hasin DS, Cao DC (2014) Alcohol challenge responses predict future alcohol use disorder symptoms: a 6-year prospective study. Biol Psychiatry 75:798–806
King AC, Hasin D, O'Connor SJ, McNamara PJ, Cao DC (2016) A prospective 5-year re-examination of alcohol response in heavy drinkers progressing in alcohol use disorder. Biol Psychiatry 79:489–498
Kirkpatrick MG, Johanson CE, de Wit H (2013) Personality and the acute subjective effects of d-amphetamine in humans. J Psychopharmacol 27:256–264
Leeman RF, Ralevski E, Limoncelli D, Pittman B, O'Malley SS, Petrakis IL (2014) Relationships between impulsivity and subjective response in an IV ethanol paradigm. Psychopharmacology 231:2867–2876
Logan GD, Schachar RJ, Tannock R (1997) Impulsivity and inhibitory control. Psychol Sci 8:60–64
Logue SF, Swartz RJ, Wehner JM (1998) Genetic correlation between performance on an appetitive-signaled nosepoke task and voluntary ethanol consumption. Alcohol Clin Exp Res 22:1912–1920
Marczinski CA, Combs SW, Fillmore MT (2007) Increased sensitivity to the disinhibiting effects of alcohol in binge drinkers. Psychol Addict Behav 21:346–354
Martin CS, Earleywine M, Musty RE, Perrine MW, Swift RM (1993) Development and validation of the biphasic alcohol effects scale. Alcohol Clin Exp Res 17:140–146
Matthews JNS, Altman DG, Campbell MJ, Royston P (1990) Analysis of serial measurements in medical research. Br Med J 300:230–235
Mulvihill LE, Skilling TA, Vogel-Sprott M (1997) Alcohol and the ability to inhibit behavior in men and women. J Stud Alcohol 58:600–605
Perry JL, Carroll ME (2008) The role of impulsive behavior in drug abuse. Psychopharmacology 200:1–26
Quinn PD, Fromme K (2011) Subjective response to alcohol challenge: a quantitative review. Alcohol Clin Exp Res 35:1759–1770
Quinn PD, Fromme K (2016) Individual differences in subjective alcohol responses and alcohol-related disinhibition. Exp Clin Psychopharmacol 24:90–99
Rhodes JD, Hawk LW (2016) Smoke and mirrors: the overnight abstinence paradigm as an index of disrupted cognitive function. Psychopharmacology 233:1395–1404
Robertson CL, Ishibashi K, Mandelkern MA, Brown AK, Ghahremani DG, Sabb F, Bilder R, Cannon T, Borg J, London ED (2015) Striatal D1- and D2-type dopamine receptors are linked to motor response inhibition in human subjects. J Neurosci 35:5990–5997
Rubio G, Jimenez M, Rodriguez-Jimenez R, Martinez I, Avila C, Ferre F, Jimenez-Arriero MA, Ponce G, Palomo T (2008) The role of behavioral impulsivity in the development of alcohol dependence: a 4-year follow-up study. Alcohol Clin Exp Res 32:1681–1687
Schuckit MA (1994) Low level of response to alcohol as a predictor of future alcoholism. Am J Psychiatry 151:184–189
Schuckit MA, Smith TL, Trim RS, Allen RC, Fukukura T, Knight EE, Cesario EM, Kreikebaum SA (2011) A prospective evaluation of how a low level of response to alcohol predicts later heavy drinking and alcohol problems. Am J Drug Alcohol Abuse 37:479–486
Tolentino NJ, Wierenga CE, Hall S, Tapert SF, Paulus MP, Liu TT, Smith TL, Schuckit MA (2011) Alcohol effects on cerebral blood flow in subjects with low and high responses to alcohol. Alcohol Clin Exp Res 35:1034–1040
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 D-2 receptor levels. Am J Psychiatry 156:1440–1443
Volkow ND, Wang GJ, Fowler JS, Thanos P, 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
Weafer J, de Wit H (2013) Inattention, impulsive action, and subjective response to d-amphetamine. Drug Alcohol Depend 133:127–133
Weafer J, Mitchell SH, de Wit H (2014) Recent translational findings on impulsivity in relation to drug abuse. Curr Addict Rep 1:289–300
Weafer J, Gallo DA, de Wit H (2016) Effect of alcohol on encoding and consolidation of memory for alcohol-related images. Alcohol Clin Exp Res 40:1540–1547
Weafer J, Gorka SM, Hedeker D, Dzemidzic M, Kareken DA, Phan KL, de Wit H (2017) Associations between behavioral and neural correlates of inhibitory control and amphetamine reward sensitivity. Neuropsychopharmacology 42:1905–1913
Weafer J, Ross TJ, O'Connor S, Stein EA, de Wit H, Childs E (2018) Striatal activity correlates with stimulant-like effects of alcohol in healthy volunteers. Neuropsychopharmacology 43:2532–2538
Wilhelm CJ, Reeves JM, Phillips TJ, Mitchell SH (2007) Mouse lines selected for alcohol consumption differ on certain measures of impulsivity. Alcohol Clin Exp Res 31:1839–1845
Funding
This research was supported by the National Institute on Drug Abuse Grants R21 DA037642 (HdW), R01 DA002812 (HdW, KLP), and National Institute on Alcohol Abuse and Alcoholism Grant K01 AA024519 (JW).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Weafer, J., Phan, K.L. & de Wit, H. Poor inhibitory control is associated with greater stimulation and less sedation following alcohol. Psychopharmacology 237, 825–832 (2020). https://doi.org/10.1007/s00213-019-05420-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-019-05420-y