Skip to main content

Effect of d-amphetamine on emotion-potentiated startle in healthy humans: implications for psychopathy and antisocial behaviour

Abstract

Rationale

An emerging literature associates increased dopaminergic neurotransmission with altered brain response to aversive stimuli in humans. The direction of the effect of dopamine on aversive motivation, however, remains unclear, with some studies reporting increased and others decreased amygdala activation to aversive stimuli following the administration of dopamine agonists. Potentiation of the startle response by aversive foreground stimuli provides an objective and directional measure of emotional reactivity and is considered useful as an index of the emotional effects of different drugs.

Objective

We investigated the effects of two doses of d-amphetamine (5 and 10 mg), compared to placebo, for the first time to our knowledge, using the affect–startle paradigm.

Method

The study employed a between-subjects, double-blind design, with three conditions: 0 mg (placebo), and 5 and 10 mg d-amphetamine (initially n = 20/group; final sample: n = 18, placebo; n = 18, 5 mg; n = 16, 10 mg). After drug/placebo administration, startle responses (eyeblinks) to intermittent noise probes were measured during viewing of pleasant, neutral and unpleasant images. Participants’ general and specific impulsivity and fear-related personality traits were also assessed.

Results

The three groups were comparable on personality traits. Only the placebo group showed significant startle potentiation by unpleasant, relative to neutral, images; this effect was absent in both 5- and 10-mg d-amphetamine groups (i.e. the same effect of d-amphetamine observed at different doses in different people).

Conclusions

Our findings demonstrate a reduced aversive emotional response under d-amphetamine and may help to account for the known link between the use of psychostimulant drugs and antisocial behaviour.

This is a preview of subscription content, access via your institution.

Fig. 1

Notes

  1. 1.

    We conducted comparable analyses for latency of response but no effects were found.

References

  1. Aldhafeeri FM, Mackenzie I, Kay T, Alghamdi J, Sluming V (2012) Regional brain responses to pleasant and unpleasant IAPS pictures: different networks. Neurosci Lett 512:94–98

    PubMed  Article  CAS  Google Scholar 

  2. Benning SD, Patrick CJ, Iacono WG (2005) Psychopathy, startle blink modulation, and electrodermal reactivity in twin men. Psychophysiology 42:753–762

    PubMed  Article  Google Scholar 

  3. Berridge KC, Kringelbach ML (2008) Affective neuroscience of pleasure: Reward in humans and animals. Psychopharmacology 199:457–480

    PubMed  Article  CAS  Google Scholar 

  4. Bijlsma EY, de Jongh R, Olivier B, Groenink L (2010) Fear-potentiated startle, but not light-enhanced startle, is enhanced by anxiogenic drugs. Pharmacol Biochem Behav 96:24–31

    PubMed  Article  CAS  Google Scholar 

  5. Blair RJ (2010) Neuroimaging of psychopathy and antisocial behavior: A targeted review. Curr Psychiatry Rep 12:76–82

    PubMed  Article  CAS  Google Scholar 

  6. Bódi N, Kéri S, Nagy H, Moustafa A, Myers CE, Daw N, Dibó G, Takáts A, Bereczki D, Gluck MA (2009) Reward-learning and the novelty-seeking personality: A between- and within-subjects study of the effects of dopamine agonists on young Parkinson’s patients. Brain 132:2385–2395

    PubMed  Article  Google Scholar 

  7. Buchanan TW, Tranel D, Adolphs R (2004) Anteromedial temporal lobe damage blocks startle modulation by fear and disgust. Behav Neurosci 118:429–437

    PubMed  Article  Google Scholar 

  8. Buckholtz JW, Treadway MT, Cowen RL, Woodward ND, Benning SD, Li R, Ansari MS, Baldwin RM, Schwartzman AN, Shelby ES, Smith CE, Cole D, Kessler RM, Zald DH (2010) Mesolimbic dopamine reward system hypersensitivity in individuals with psychopathic traits. Nat Neurosci 13:419–421

    PubMed  Article  CAS  Google Scholar 

  9. Cloninger CR (1988) The tridimensional personality questionnaire. Washington University School of Medicine, Department of Psychiatry and Genetics

    Google Scholar 

  10. Corr PJ (2010) The psychoticism-psychopathy continuum: A model of core neuropsychological deficits. Pers Indiv Diff 48:695–703

    Article  Google Scholar 

  11. Corr PJ, Wilson GD, Fotiadou M, Kumari V, Gray NS, Checkley S, Gray JA (1995) Personality and affective modulation of the startle reflex. Pers Indiv Diff 19:543–553

    Article  Google Scholar 

  12. Corr PJ, Kumari V, Wilson GD, Checkley S, Gray JA (1997) Harm avoidance and affective modulation of the startle reflex: A replication. Pers Indiv Diff 22:591–593

    Article  Google Scholar 

  13. Cools R, Altamirano L, D’Esposito M (2006) Reversal learning in Parkinson’s disease depends on medication status and outcome valence. Neuropsychologia 44:1663–1673

    PubMed  Article  Google Scholar 

  14. Davis M, Falls M, Campeau S, Kim M (1993) Fear potentiated startle: A neural and pharmacological analysis. Behav Brain Res 58:175–198

    PubMed  Article  CAS  Google Scholar 

  15. Delaveau P, Salgado-Pineda P, Micallef-Roll J, Blin O (2007) Amygdala activation modulated by levodopa during emotional recognition processing in healthy volunteers: A double-blind, placebo-controlled study. J Clin Psychopharm 27:692–697

    Article  CAS  Google Scholar 

  16. Eysenck SBG, Pearson PR, Easting G, Allsopp JF (1985) Age norms for impulsiveness, venturesomeness and empathy in adults. Pers Indiv Diff 6:613–619

    Article  Google Scholar 

  17. Fibiger CM, Phillips AG (1998) Mesocorticolimbic dopamine systems of reward. In: Kalivas PW, Nemeroff CB (eds) The midbrain periaqueductal grey matter: functional, anatomical and immnunohistochemical organisation. Plenum, New York

    Google Scholar 

  18. Frank MJ, Seeberger LC, O’reilly RC (2004) By carrot or by stick: Cognitive reinforcement learning in parkinsonism. Science 306:1940–1943

    PubMed  Article  CAS  Google Scholar 

  19. Frank MJ, Samanta J, Moustafa AA, Sherman SJ (2007) Hold your horses: Impulsivity, deep brain stimulation, and medication in parkinsonism. Science 318:1309–1312

    PubMed  Article  CAS  Google Scholar 

  20. Fridell M, Hesse M, Jaeger MM, Kuhlhorn E (2008) Antisocial personality disorder as a predictor of criminal behaviour in a longitudinal study of a cohort of abusers of several classes of drugs: Relation to type of substance and type of crime. Addict Behav 33:799–811

    PubMed  Article  Google Scholar 

  21. Funayama ES, Grillon C, Davis M, Phelps EA (2001) A double dissociation in the affective modulation of startle in humans: Effects of unilateral temporal lobectomy. J Cogn Neurosci 13:721–729

    PubMed  Article  CAS  Google Scholar 

  22. Gao Y, Glenn AL, Schug RA, Yang Y, Raine A (2009) The neurobiology of psychopathy: A neurodevelopmental perspective. Can J Psychiatry 54:813–283

    PubMed  Google Scholar 

  23. Giakoumaki SG, Bitsios P, Frangou S, Roussos P, Aasen I, Galea A, Kumari V (2010) Low baseline startle and deficient affective startle modulation in remitted bipolar disorder patients and their unaffected siblings. Psychophysiol 47:659–668

    Google Scholar 

  24. Graef S, Biele G, Krugel LK, Marzinzik F, Wahl M, Wotka J, Klostermann F, Heekeren HR (2010) Differential influence of levodopa on reward-based learning in Parkinson’s disease. Front Hum Neurosci 4:169

    PubMed  Article  Google Scholar 

  25. Gray JA (1987) The psychology of fear and stress. Cambridge University Press, Cambridge

    Google Scholar 

  26. Gray JA (1991) Neural systems of motivation, emotion and affect. In: Maden J (ed) Neurobiology of Learning, Emotion and Affect. Raven, New York

    Google Scholar 

  27. Hariri AR, Mattay VS, Tessitore A, Fera F, Smith WS, Weinberger DR (2002) Dextroamphetamine modulates the response of the human amygdala. Neuropsychopharmacol 27:1036–1040

    Article  CAS  Google Scholar 

  28. Herpertz SC, Werth U, Lukas G, Qunaibi M, Schuerkens A, Kunert HJ, Freese R, Flesch M, Mueller-Isberner R, Osterheider M, Sass H (2001) Emotion in criminal offenders with psychopathy and borderline personality disorder. Arch Gen Psychiatry 58:737–745

    PubMed  Article  CAS  Google Scholar 

  29. Hung AS, Tsui TY, Lam JC, Wai MS, Chan WM, Yew DT (2011) Serotonin and its receptors in the human CNS with new findings—a mini review. Curr Med Chem 18:5281–5288

    PubMed  Article  CAS  Google Scholar 

  30. Kaviani H, Gray JA, Checkley SA, Raven PW, Wilson GD, Kumari V (2004) Affective modulation of the startle response in depression: Influence of the severity of depression, anhedonia, and anxiety. J Affect Disord 83:21–31

    PubMed  Article  CAS  Google Scholar 

  31. Kobayakawa M, Tsuruya N, Kawamura M (2010) Sensitivity to reward and punishment in Parkinson’s disease: An analysis of behavioral patterns using a modified version of the Iowa gambling task. Parkinsonism Relat Disord 16:453–457

    PubMed  Article  Google Scholar 

  32. Koch M (1999) The neurobiology of startle. Prog Neurobiol 59:107–128

    PubMed  Article  CAS  Google Scholar 

  33. Koch M, Schmid A, Schnitzler HU (1996) Pleasure-attenuation of startle is disrupted by lesions of the nucleus accumbens. Neuroreport 7:1442–1446

    PubMed  Article  CAS  Google Scholar 

  34. Kroner S, Rosenkranz JA, Grace AA, Barrionuevo G (2005) Dopamine modulates excitability of basolateral amygdala neurons in vitro. J Neurophysiol 93:1598–1610

    PubMed  Article  CAS  Google Scholar 

  35. Kumari V, Cotter P, Corr PJ, Gray JA, Checkley SA (1996) Effect of clonidine on the human acoustic startle reflex. Psychopharmacology 123(4):353–360

    PubMed  Article  CAS  Google Scholar 

  36. Kumari V, Kaviani H, Raven PW, Gray JA, Checkley SA (2001) Enhanced startle reactions to acoustic stimuli in patients with obsessive–compulsive disorder. Am J Psychiatry 158:134–136

    PubMed  Article  CAS  Google Scholar 

  37. Lang PJ, Bradley MM (2005) International affective picture system (IAPS): Affective ratings of pictures and instruction manual. Technical Report University of Florida, Gainesville FL

    Google Scholar 

  38. Lang PJ, Bradley MM, Cuthbert BN (1990) Emotion, attention, and the startle reflex. Psychol Rev 97:377–395

    PubMed  Article  CAS  Google Scholar 

  39. Lang PJ, Davis M, Ohman A (2000) Fear and anxiety: Animal models and human cognitive psychophysiology. J Affect Disord 61:137–159

    PubMed  Article  CAS  Google Scholar 

  40. Miller TR, Levy DT, Cohen MA, Cox KLC (2006) Costs of alcohol and drug-involved crime. Prev Sci 7:333–342

    PubMed  Article  Google Scholar 

  41. Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (1998) Dopamine receptors: From structure to function. Physiol Rev 78:189–225

    PubMed  CAS  Google Scholar 

  42. Ornstein TJ, Iddon JL, Baldacchino AM, Sahakian BJ, Everitt BJ, Robbins TW (2000) Profiles of cognitive dysfunction in chronic amphetamine and heroin abusers. Neuropharmacol 23:113–126

    CAS  Google Scholar 

  43. Patin A, Hurlemann R (2011) Modulating amygdala responses to emotion: Evidence from pharmacological fMRI. Neuropsychologia 49:706–717

    PubMed  Article  Google Scholar 

  44. Patrick CJ, Bradley MM, Lang PJ (1993) Emotion in the criminal psychopath: Startle reflex modulation. J Abnorm Psychol 102:82–92

    PubMed  Article  CAS  Google Scholar 

  45. Roussos P, Giakoumaki SG, Bitsios P (2009) Cognitive and emotional processing in high novelty seeking associated with the L-DRD4 genotype. Neuropsychologia 47:1654–1659

    PubMed  Article  Google Scholar 

  46. Takahashi H, Yahata N, Koeda M, Takano A, Asai K, Suhara T, Okubo Y (2005) Effects of dopaminergic and serotonergic manipulation on emotional processing: A pharmacological fMRI study. NeuroImage 27:991–1001

    PubMed  Article  Google Scholar 

  47. Vaidyanathan U, Hall JR, Patrick CJ, Bernat EM (2011) Clarifying the role of defensive reactivity deficits in psychopathy and antisocial personality using startle reflex methodology. J Ab Psychol 120:253–258

    Article  Google Scholar 

  48. Vrana SR, Spence EL, Lang PJ (1988) The startle probe response: A new measure of emotion? J Ab Psychol 97:487–491

    Article  CAS  Google Scholar 

  49. West WB, Van Groll BJ, Appel JB (1995) Stimulus effects of d-amphetamine II: DA, NE, and 5-HT mechanisms. Pharmacol Biochem Behav 51:69–76

    PubMed  Article  CAS  Google Scholar 

  50. Wolpe J, Lang PJ (1969) Fear survey schedule. Educational and industrial testing service, San Diego, CA

    Google Scholar 

Download references

Acknowledgments

We are grateful to (late) Professor Jeffrey Gray, Professor Stuart A Checkley, Dr. Jasper Thornton, Dr. Claire Capstick and Ms Lucia Poon for help with the study. This work was supported by funds from the Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King’s College London, and the South London and Maudsley NHS Foundation Trust for some of Professor Veena Kumari’s time.

Conflict of interest

The authors declare no conflict of interest.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Veena Kumari.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Corr, P.J., Kumari, V. Effect of d-amphetamine on emotion-potentiated startle in healthy humans: implications for psychopathy and antisocial behaviour. Psychopharmacology 225, 373–379 (2013). https://doi.org/10.1007/s00213-012-2824-8

Download citation

Keywords

  • d-amphetamine
  • Dopamine
  • Startle potentiation
  • Emotion
  • Affect
  • Antisocial behaviour
  • Psychopathic disorder