Effect of d-amphetamine on emotion-potentiated startle in healthy humans: implications for psychopathy and antisocial behaviour
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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.
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.
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.
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).
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.
Keywordsd-amphetamine Dopamine Startle potentiation Emotion Affect Antisocial behaviour Psychopathic disorder
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.
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