title: Dopamine Regulates Approach-Avoidance in Human Sensation-Seeking.
abstract: BACKGROUND
  Sensation-seeking is a trait that constitutes an important vulnerability factor for a variety of psychopathologies with high social cost. However, little is understood either about the mechanisms underlying motivation for intense sensory experiences or their neuropharmacological modulation in humans.
  
  
  METHODS
  Here, we first evaluate a novel paradigm to investigate sensation-seeking in humans. This test probes the extent to which participants choose either to avoid or self-administer an intense tactile stimulus (mild electric stimulation) orthogonal to performance on a simple economic decision-making task. Next we investigate in a different set of participants whether this behavior is sensitive to manipulation of dopamine D2 receptors using a within-subjects, placebo-controlled, double-blind design.
  
  
  RESULTS
  In both samples, individuals with higher self-reported sensation-seeking chose a greater proportion of mild electric stimulation-associated stimuli, even when this involved sacrifice of monetary gain. Computational modelling analysis determined that people who assigned an additional positive economic value to mild electric stimulation-associated stimuli exhibited speeding of responses when choosing these stimuli. In contrast, those who assigned a negative value exhibited slowed responses. These findings are consistent with involvement of low-level, approach-avoidance processes. Furthermore, the D2 antagonist haloperidol selectively decreased the additional economic value assigned to mild electric stimulation-associated stimuli in individuals who showed approach reactions to these stimuli under normal conditions (behavioral high-sensation seekers).
  
  
  CONCLUSIONS
  These findings provide the first direct evidence of sensation-seeking behavior being driven by an approach-avoidance-like mechanism, modulated by dopamine, in humans. They provide a framework for investigation of psychopathologies for which extreme sensation-seeking constitutes a vulnerability factor.
authors: Institute of Cognitive Neuroscience (Ms Norbury and Drs Winston and Roiser), Wellcome Trust Centre for Neuroimaging (Drs Kurth-Nelson and Winston), Max Plank-UCL Centre for Computational Psychiatry and Ageing (Dr Kurth-Nelson), University College London, London, United Kingdom; Department of Experimental Psychology and Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom (Professor Husain). agnes.norbury.10@ucl.ac.uk.
authors: Agnes
authors: A
authors: Norbury
authors: Institute of Cognitive Neuroscience (Ms Norbury and Drs Winston and Roiser), Wellcome Trust Centre for Neuroimaging (Drs Kurth-Nelson and Winston), Max Plank-UCL Centre for Computational Psychiatry and Ageing (Dr Kurth-Nelson), University College London, London, United Kingdom; Department of Experimental Psychology and Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom (Professor Husain).
authors: Zeb
authors: Z
authors: Kurth-Nelson
authors: Institute of Cognitive Neuroscience (Ms Norbury and Drs Winston and Roiser), Wellcome Trust Centre for Neuroimaging (Drs Kurth-Nelson and Winston), Max Plank-UCL Centre for Computational Psychiatry and Ageing (Dr Kurth-Nelson), University College London, London, United Kingdom; Department of Experimental Psychology and Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom (Professor Husain).
authors: Joel S
authors: JS
authors: Winston
authors: Institute of Cognitive Neuroscience (Ms Norbury and Drs Winston and Roiser), Wellcome Trust Centre for Neuroimaging (Drs Kurth-Nelson and Winston), Max Plank-UCL Centre for Computational Psychiatry and Ageing (Dr Kurth-Nelson), University College London, London, United Kingdom; Department of Experimental Psychology and Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom (Professor Husain).
authors: Jonathan P
authors: JP
authors: Roiser
authors: Institute of Cognitive Neuroscience (Ms Norbury and Drs Winston and Roiser), Wellcome Trust Centre for Neuroimaging (Drs Kurth-Nelson and Winston), Max Plank-UCL Centre for Computational Psychiatry and Ageing (Dr Kurth-Nelson), University College London, London, United Kingdom; Department of Experimental Psychology and Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom (Professor Husain).
authors: Masud
authors: M
authors: Husain
mesh_terms: D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D003198:Computer Simulation; D003657:Decision Making / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists / Q000494:pharmacology; D004311:Double-Blind Method; D004558:Electric Stimulation; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D007206:Individuality; D008297:Male; D018803:Models, Economic; D008960:Models, Psychological; D009042:Motivation / Q000187:drug effects / Q000502:physiology*; D009483:Neuropsychological Tests; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012309:Risk-Taking; D012653:Self Stimulation; D012677:Sensation; D055815:Young Adult
chemical_list: C581293:DRD2 protein, human; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D006220:Haloperidol; D004298:Dopamine
keywords: D2 antagonist; addiction; dopamine; impulsivity; sensation-seeking