Norbury, A; Kurth-Nelson, Z; Winston, JS; Roiser, JP; Husain, M; (2015) Dopamine regulates approach-avoidance in human sensation-seeking. International Journal of Neuropsychopharmacology , 18 (10) 10.1093/ijnp/pyv041.

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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 or MES), orthogonal to performance on a simple economic decision-making task. Next we investigate in a different set of participants whether this behaviour 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 MES-associated stimuli, even when this involved sacrifice of monetary gain. Computational modelling analysis determined that people who assigned an additional positive economic value to MES-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 MES-associated stimuli in individuals who showed approach reactions to these stimuli under normal conditions ('behavioural high sensation-seekers'). Conclusions These findings provide the first direct evidence of sensation-seeking behaviour 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.

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