TY - JOUR TI - Effects of dopamine D2/3 and opioid receptor antagonism on the trade-off between model-based and model-free behaviour in healthy volunteers AU - Mikus, Nace AU - Korb, Sebastian AU - Massaccesi, Claudia AU - Gausterer, Christian AU - Graf, Irene AU - Willeit, Matthäus AU - Eisenegger, Christoph AU - Lamm, Claus AU - Silani, Giorgia AU - Mathys, Christoph A2 - Kahnt, Thorsten A2 - Taffe, Michael A VL - 11 PY - 2022 DA - 2022/12/05 SP - e79661 C1 - eLife 2022;11:e79661 DO - 10.7554/eLife.79661 UR - https://doi.org/10.7554/eLife.79661 AB - Human behaviour requires flexible arbitration between actions we do out of habit and actions that are directed towards a specific goal. Drugs that target opioid and dopamine receptors are notorious for inducing maladaptive habitual drug consumption; yet, how the opioidergic and dopaminergic neurotransmitter systems contribute to the arbitration between habitual and goal-directed behaviour is poorly understood. By combining pharmacological challenges with a well-established decision-making task and a novel computational model, we show that the administration of the dopamine D2/3 receptor antagonist amisulpride led to an increase in goal-directed or ‘model-based’ relative to habitual or ‘model-free’ behaviour, whereas the non-selective opioid receptor antagonist naltrexone had no appreciable effect. The effect of amisulpride on model-based/model-free behaviour did not scale with drug serum levels in the blood. Furthermore, participants with higher amisulpride serum levels showed higher explorative behaviour. These findings highlight the distinct functional contributions of dopamine and opioid receptors to goal-directed and habitual behaviour and support the notion that even small doses of amisulpride promote flexible application of cognitive control. KW - reinforcement learning KW - cognitive control KW - decision-making JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -