, Volume 204, Issue 4, pp 679–692 | Cite as

Ethanol effects on impulsivity in two mouse strains: similarities to diazepam and ketamine

  • Yolanda Peña Oliver
  • Tamzin L. Ripley
  • David N. Stephens
Original Investigation



The effects of ethanol on attention and impulsivity have been contradictory.


The aim of the present investigation is to study the effects of acute ethanol administration in measures of attention and response control in the five-choice serial reaction time task (5-CSRTT) in two strains of mice, C57BL/6JOlaHsd and CD1.

Materials and methods

Mice were trained in the 5-CSRTT and then were injected intraperitoneally (i.p.) with 0, 0.5, 1 and 2 g/kg ethanol before testing under standard parameters and in a long inter-trial interval (ITI) session, which promotes the emergence of premature responses, a measure of poor inhibitory control. To examine if the effects of ethanol in the 5-CSRTT were due to its actions at GABAA receptors or at NMDA receptors, the GABAA receptor agonist diazepam (1 and 2 mg/kg, i.p.) and the non-competitive NMDA antagonist ketamine (10 and 20 mg/kg, i.p.) were tested in long ITI sessions.


Ethanol did not affect attention or impulsivity in the standard procedure, but increased premature responding in long ITI sessions. The effects of ethanol were mimicked by diazepam in both strains of mice, whereas ketamine increased premature responding only in the CD1 strain.


Ethanol's ability to increase impulsivity in the 5-CSRTT is mediated by both common and different neurotransmitter systems in the two strains of mice and is dependent on the task's parameters. Furthermore, ethanol did not decrease response accuracy, suggesting that attentional mechanisms are preserved after acute ethanol in mice and that the increases in impulsive behaviour are independent of attentional performance.


Attention Impulsivity 5-CSRTT Ethanol Diazepam Ketamine Mouse 



This work was carried out within the framework of the IMAGEN consortium. IMAGEN receives research funding from the European Community's Sixth Framework Programme (LSHM-CT-2007-037286). This paper reflects only the authors' views and the community is not liable for any use that may be made of the information contained therein.


  1. Billings CE, Demosthenes T, White TR, O'Hara DB (1991) Effects of alcohol on pilot performance in simulated flight. Aviat Space Environ Med 62:233–235PubMedGoogle Scholar
  2. Bizarro L, Patel S, Stolerman IP (2003) Comprehensive deficits in performance of an attentional task produced by co-administering alcohol and nicotine to rats. Drug Alcohol Depend 72:287–295PubMedCrossRefGoogle Scholar
  3. Cabib S, Puglisi-Allegra S, Ventura R (2002) The contribution of comparative studies in inbred strains of mice to the understanding of the hyperactive phenotype. Behav Brain Res 130:103–109PubMedCrossRefGoogle Scholar
  4. Carli M, Robbins TW, Evenden JL, Everitt BJ (1983) Effects of lesions to ascending noradrenergic neurones on performance of a 5-choice serial reaction task in rats; implications for theories of dorsal noradrenergic bundle function based on selective attention and arousal. Behav Brain Res 9:361–380PubMedCrossRefGoogle Scholar
  5. Carli M, Baviera M, Invernizzi RW, Balducci C (2006) Dissociable contribution of 5-HT1A and 5-HT2A receptors in the medial prefrontal cortex to different aspects of executive control such as impulsivity and compulsive perseveration in rats. Neuropsychopharmacology 31:757–767PubMedCrossRefGoogle Scholar
  6. Cheng RK, MacDonald CJ, Meck WH (2006) Differential effects of cocaine and ketamine on time estimation: implications for neurobiological models of interval timing. Pharmacol Biochem Behav 85:114–122PubMedCrossRefGoogle Scholar
  7. Cherpitel CJ (1993) Alcohol and injuries: a review of international emergency room studies. Addiction 88:923–937PubMedCrossRefGoogle Scholar
  8. Cherpitel CJ (1999) Substance use, injury, and risk-taking dispositions in the general population. Alcohol Clin Exp Res 23:121–126PubMedGoogle Scholar
  9. Chudasama Y, Passetti F, Rhodes SE, Lopian D, Desai A, Robbins TW (2003) Dissociable aspects of performance on the 5-choice serial reaction time task following lesions of the dorsal anterior cingulate, infralimbic and orbitofrontal cortex in the rat: differential effects on selectivity, impulsivity and compulsivity. Behav Brain Res 146:105–119PubMedCrossRefGoogle Scholar
  10. Cole SO (1990) Diazepam-induced impairment of a go-no go successive discrimination. Behav Neural Biol 53:371–377PubMedCrossRefGoogle Scholar
  11. Cole BJ, Robbins TW (1989) Effects of 6-hydroxydopamine lesions of the nucleus accumbens septi on performance of a 5-choice serial reaction time task in rats: implications for theories of selective attention and arousal. Behav Brain Res 33:165–179PubMedCrossRefGoogle Scholar
  12. Crawley JN, Belknap JK, Collins A, Crabbe JC, Frankel W, Henderson N, Hitzemann RJ, Maxson SC, Miner LL, Silva AJ, Wehner JM, Wynshaw-Boris A, Paylor R (1997) Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies. Psychopharmacology (Berl) 132:107–124CrossRefGoogle Scholar
  13. Critchlow B (1986) The powers of John Barleycorn. Beliefs about the effects of alcohol on social behavior. Am Psychol 41:751–764PubMedCrossRefGoogle Scholar
  14. 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 315:1267–1270PubMedCrossRefGoogle Scholar
  15. Dalley JW, Mar AC, Economidou D, Robbins TW (2008) Neurobehavioral mechanisms of impulsivity: fronto-striatal systems and functional neurochemistry. Pharmacol Biochem Behav 90:250–260PubMedCrossRefGoogle Scholar
  16. Dougherty DM, Moeller FG, Steinberg JL, Marsh DM, Hines SE, Bjork JM (1999) Alcohol increases commission error rates for a continuous performance test. Alcohol Clin Exp Res 23:1342–1351PubMedGoogle Scholar
  17. Dougherty DM, Marsh DM, Moeller FG, Chokshi RV, Rosen VC (2000) Effects of moderate and high doses of alcohol on attention, impulsivity, discriminability, and response bias in immediate and delayed memory task performance. Alcohol Clin Exp Res 24:1702–1711PubMedCrossRefGoogle Scholar
  18. Dougherty DM, Marsh-Richard DM, Hatzis ES, Nouvion SO, Mathias CW (2008) A test of alcohol dose effects on multiple behavioral measures of impulsivity. Drug Alcohol Depend 96:111–120PubMedCrossRefGoogle Scholar
  19. Ericksen KP, Trocki KF (1994) Sex, alcohol and sexually transmitted diseases: a national survey. Fam Plann Perspect 26:257–263PubMedCrossRefGoogle Scholar
  20. Evenden JL (1999) Varieties of impulsivity. Psychopharmacology (Berl) 146:348–361CrossRefGoogle Scholar
  21. Evenden JL, Ryan CN (1999) The pharmacology of impulsive behaviour in rats VI: the effects of ethanol and selective serotonergic drugs on response choice with varying delays of reinforcement. Psychopharmacology (Berl) 146:413–421CrossRefGoogle Scholar
  22. Floresco SB, Tse MT, Ghods-Sharifi S (2008) Dopaminergic and glutamatergic regulation of effort- and delay-based decision making. Neuropsychopharmacology 33:1966–1979PubMedCrossRefGoogle Scholar
  23. Givens B (1997) Effect of ethanol on sustained attention in rats. Psychopharmacology (Berl) 129:135–140CrossRefGoogle Scholar
  24. Givens B, McMahon K (1997) Effects of ethanol on nonspatial working memory and attention in rats. Behav Neurosci 111:275–282PubMedCrossRefGoogle Scholar
  25. Greco B, Carli M (2006) Reduced attention and increased impulsivity in mice lacking NPY Y2 receptors: relation to anxiolytic-like phenotype. Behav Brain Res 169:325–334PubMedCrossRefGoogle Scholar
  26. Grottick AJ, Higgins GA (2000) Effect of subtype selective nicotinic compounds on attention as assessed by the five-choice serial reaction time task. Behav Brain Res 117:197–208PubMedCrossRefGoogle Scholar
  27. Hahn B, Shoaib M, Stolerman IP (2002) Nicotine-induced enhancement of attention in the five-choice serial reaction time task: the influence of task demands. Psychopharmacology (Berl) 162:129–137CrossRefGoogle Scholar
  28. Higgins GA, Ballard TM, Huwyler J, Kemp JA, Gill R (2003a) Evaluation of the NR2B-selective NMDA receptor antagonist Ro 63-1908 on rodent behaviour: evidence for an involvement of NR2B NMDA receptors in response inhibition. Neuropharmacology 44:324–341PubMedCrossRefGoogle Scholar
  29. Higgins GA, Enderlin M, Haman M, Fletcher PJ (2003b) The 5-HT2A receptor antagonist M100, 907 attenuates motor and ‘impulsive-type’ behaviours produced by NMDA receptor antagonism. Psychopharmacology (Berl) 170:309–319CrossRefGoogle Scholar
  30. Maylor EA, Rabbitt PM (1993) Alcohol, reaction time and memory: a meta-analysis. Br J Psychol 84(Pt 3):301–317PubMedGoogle Scholar
  31. McGaughy J, Sarter M (1995) Behavioral vigilance in rats: task validation and effects of age, amphetamine, and benzodiazepine receptor ligands. Psychopharmacology (Berl) 117:340–357CrossRefGoogle Scholar
  32. Moselhy HF, Georgiou G, Kahn A (2001) Frontal lobe changes in alcoholism: a review of the literature. Alcohol Alcohol 36:357–368PubMedGoogle Scholar
  33. Mulvihill LE, Skilling TA, Vogel-Sprott M (1997) Alcohol and the ability to inhibit behavior in men and women. J Stud Alcohol 58:600–605PubMedGoogle Scholar
  34. Murphy ER, Dalley JW, Robbins TW (2005) Local glutamate receptor antagonism in the rat prefrontal cortex disrupts response inhibition in a visuospatial attentional task. Psychopharmacology (Berl) 179:99–107CrossRefGoogle Scholar
  35. Olmstead MC, Hellemans KG, Paine TA (2006) Alcohol-induced impulsivity in rats: an effect of cue salience? Psychopharmacology (Berl) 184:221–228CrossRefGoogle Scholar
  36. Ortner CN, MacDonald TK, Olmstead MC (2003) Alcohol intoxication reduces impulsivity in the delay-discounting paradigm. Alcohol Alcohol 38:151–156PubMedGoogle Scholar
  37. Patel S, Stolerman IP, Asherson P, Sluyter F (2006) Attentional performance of C57BL/6 and DBA/2 mice in the 5-choice serial reaction time task. Behav Brain Res 170:197–203PubMedCrossRefGoogle Scholar
  38. Pattij T, Vanderschuren LJ (2008) The neuropharmacology of impulsive behaviour. Trends Pharmacol Sci 29:192–199PubMedCrossRefGoogle Scholar
  39. Pattij T, Janssen MC, Vanderschuren LJ, Schoffelmeer AN, van Gaalen MM (2007) Involvement of dopamine D1 and D2 receptors in the nucleus accumbens core and shell in inhibitory response control. Psychopharmacology (Berl) 191:587–598CrossRefGoogle Scholar
  40. Petry NM (2001) Delay discounting of money and alcohol in actively using alcoholics, currently abstinent alcoholics, and controls. Psychopharmacology (Berl) 154:243–250CrossRefGoogle Scholar
  41. Poulos CX, Parker JL, Le DA (1998) Increased impulsivity after injected alcohol predicts later alcohol consumption in rats: evidence for “loss-of-control drinking” and marked individual differences. Behav Neurosci 112:1247–1257PubMedCrossRefGoogle Scholar
  42. Puumala T, Sirvio J (1998) Changes in activities of dopamine and serotonin systems in the frontal cortex underlie poor choice accuracy and impulsivity of rats in an attention task. Neuroscience 83:489–499PubMedCrossRefGoogle Scholar
  43. Puumala T, Ruotsalainen S, Jakala P, Koivisto E, Riekkinen P Jr, Sirvio J (1996) Behavioral and pharmacological studies on the validation of a new animal model for attention deficit hyperactivity disorder. Neurobiol Learn Mem 66:198–211PubMedCrossRefGoogle Scholar
  44. Rezvani AH, Levin ED (2003) Nicotine–alcohol interactions and attentional performance on an operant visual signal detection task in female rats. Pharmacol Biochem Behav 76:75–83PubMedCrossRefGoogle Scholar
  45. Richards JB, Zhang L, Mitchell SH, de Wit H (1999) Delay or probability discounting in a model of impulsive behavior: effect of alcohol. J Exp Anal Behav 71:121–143PubMedCrossRefGoogle Scholar
  46. Robbins TW (2002) The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry. Psychopharmacology (Berl) 163:362–380CrossRefGoogle Scholar
  47. Roberto M, Madamba SG, Stouffer DG, Parsons LH, Siggins GR (2004a) Increased GABA release in the central amygdala of ethanol-dependent rats. J Neurosci 24:10159–10166PubMedCrossRefGoogle Scholar
  48. Roberto M, Schweitzer P, Madamba SG, Stouffer DG, Parsons LH, Siggins GR (2004b) Acute and chronic ethanol alter glutamatergic transmission in rat central amygdala: an in vitro and in vivo analysis. J Neurosci 24:1594–1603PubMedCrossRefGoogle Scholar
  49. Rohrbaugh JW, Stapleton JM, Parasuraman R, Frowein HW, Adinoff B, Varner JL, Zubovic EA, Lane EA, Eckardt MJ, Linnoila M (1988) Alcohol intoxication reduces visual sustained attention. Psychopharmacology (Berl) 96:442–446CrossRefGoogle Scholar
  50. Samson HH, Harris RA (1992) Neurobiology of alcohol abuse. Trends Pharmacol Sci 13:206–211PubMedCrossRefGoogle Scholar
  51. Shelton KL, Balster RL (1994) Ethanol drug discrimination in rats: substitution with GABA agonists and NMDA antagonists. Behav Pharmacol 5:441–451PubMedGoogle Scholar
  52. Spinella M (2004) Neurobehavioral correlates of impulsivity: evidence of prefrontal involvement. Int J Neurosci 114:95–104PubMedCrossRefGoogle Scholar
  53. Stephens DN, Cole BJ (1996) AMPA antagonists differ from NMDA antagonists in their effects on operant DRL and delayed matching to position tasks. Psychopharmacology (Berl) 126:249–259CrossRefGoogle Scholar
  54. Tarter RE, Kirisci L, Habeych M, Reynolds M, Vanyukov M (2004) Neurobehavior disinhibition in childhood predisposes boys to substance use disorder by young adulthood: direct and mediated etiologic pathways. Drug Alcohol Depend 73:121–132PubMedCrossRefGoogle Scholar
  55. Thiebot MH, Le Bihan C, Soubrie P, Simon P (1985) Benzodiazepines reduce the tolerance to reward delay in rats. Psychopharmacology (Berl) 86:147–152CrossRefGoogle Scholar
  56. Tomie A, Aguado AS, Pohorecky LA, Benjamin D (1998) Ethanol induces impulsive-like responding in a delay-of-reward operant choice procedure: impulsivity predicts autoshaping. Psychopharmacology (Berl) 139:376–382CrossRefGoogle Scholar
  57. van Gaalen MM, Brueggeman RJ, Bronius PF, Schoffelmeer AN, Vanderschuren LJ (2006) Behavioral disinhibition requires dopamine receptor activation. Psychopharmacology (Berl) 187:73–85CrossRefGoogle Scholar
  58. West R, Wilding J, French D, Kemp R, Irving A (1993) Effect of low and moderate doses of alcohol on driving hazard perception latency and driving speed. Addiction 88:527–532PubMedCrossRefGoogle Scholar
  59. Winstanley CA, Eagle DM, Robbins TW (2006a) Behavioral models of impulsivity in relation to ADHD: translation between clinical and preclinical studies. Clin Psychol Rev 26:379–395PubMedCrossRefGoogle Scholar
  60. Winstanley CA, Theobald DE, Dalley JW, Cardinal RN, Robbins TW (2006b) Double dissociation between serotonergic and dopaminergic modulation of medial prefrontal and orbitofrontal cortex during a test of impulsive choice. Cereb Cortex 16:106–114PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Yolanda Peña Oliver
    • 1
  • Tamzin L. Ripley
    • 1
  • David N. Stephens
    • 1
  1. 1.Department of PsychologyUniversity of SussexBrightonUK

Personalised recommendations