Effects of dopamine D2 and opioid receptor antagonism on the trade-off between model-based and model-free behavior in healthy volunteers

Abstract

Our daily behaviour requires a 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 D2 dopamine 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. These findings highlight the distinct functional contributions of dopamine and opioid receptors to goal-directed and habitual behaviour and support the notion that D2 receptor antagonists promote stabilisation of goal-relevant information.

Disruption of dopamine D2/D3 system function impairs the human ability to understand the mental states of other people

“…While the dopaminergic modulation of mentalising during recursive social interactions has been investigated, for instance, using multiround economic games [ 16 , 17 ], future work could expand on the existing results by investigating how dopamine modulates the attribution of mental states to human agents in face-to-face interactions. Moreover, while previous work suggests that dopamine may modulate mental state representation (given its role in model-based reasoning [ 78 ]), based on the current data, it cannot be determined whether performance differences are driven by differences in the representation, or mere inference of those mental states [ 79 ]. Second, our interpretation that the observed effects of our dopaminergic manipulation in the mental and non-mental state conditions arise from 2 separable neurochemical (i.e., mesolimbic and nigrostriatal) and mechanistic (action representation and reward processing) pathways is based on subsidiary analyses and warrants further investigation using dedicated experimental designs.…”

Untitled

“…While the dopaminergic modulation of mentalising during recursive social interactions has been investigated, for instance, using multiround economic games [16,17], future work could expand on the existing results by investigating how dopamine modulates the attribution of mental states to human agents in face-to-face interactions. Moreover, while previous work suggests that dopamine may modulate mental state representation (given its role in model-based reasoning [78]), based on the current data, it cannot be determined whether performance differences are driven by differences in the representation, or mere inference of those mental states [79]. Second, our interpretation that the observed effects of our dopaminergic manipulation in the mental and nonmental state conditions arise from 2 separable neurochemical (i.e., mesolimbic and nigrostriatal) and mechanistic (action representation and reward processing) pathways is based on subsidiary analyses and warrants further investigation using dedicated experimental designs.…”

Untitled

“…While the dopaminergic modulation of mentalising during recursive social interactions has been investigated, for instance, using multiround economic games [16,17], future work could expand on the existing results by investigating how dopamine modulates the attribution of mental states to human agents in face-to-face interactions. Moreover, while previous work suggests that dopamine may modulate mental state representation (given its role in model-based reasoning [78]), based on the current data, it cannot be determined whether performance differences are driven by differences in the representation, or mere inference of those mental states [79]. Second, our interpretation that the observed effects of our dopaminergic manipulation in the mental and nonmental state conditions arise from 2 separable neurochemical (i.e., mesolimbic and nigrostriatal) and mechanistic (action representation and reward processing) pathways is based on subsidiary analyses and warrants further investigation using dedicated experimental designs.…”