Opioid antagonism modulates wanting-related frontostriatal connectivity

Abstract

Theoretical accounts distinguish between motivational (‘wanting’) and hedonic (‘liking’) dimensions of rewards. Previous animal and human research linked wanting and liking to anatomically and neurochemically distinct brain mechanisms, but it remains unknown how the different brain regions and neurotransmitter systems interact in processing distinct reward dimensions. Here, we assessed how pharmacological manipulations of opioid and dopamine receptor activation modulate the neural processing of wanting and liking in humans in a randomized, placebo-controlled, double-blind clinical trial. Reducing opioid receptor activation with naltrexone selectively reduced wanting of rewards, which on a neural level was reflected by stronger coupling between dorsolateral prefrontal cortex and the striatum under naltrexone compared with placebo. In contrast, reducing dopaminergic neurotransmission with amisulpride revealed no robust effects on behavior or neural activity. Our findings thus provide insights into how opioid receptors mediate neural connectivity related to specifically motivational, not hedonic, aspects of rewards.

Effects of dopamine D2/3 and opioid receptor antagonism on the trade-off between model-based and model-free behaviour in healthy volunteers

“…One possibility is that opioid receptors are not crucial for model-free learning required in this task. This is in opposition to previous studies showing that acute administration of naltrexone, comparably to amisulpride, causes a reduction of cue responsivity and reward impulsivity ( Weber et al, 2016 ), decreases effort to obtain immediate primary rewards ( Korb et al, 2020 ), and decreases the wanting of rewards ( Soutschek et al, 2021 ). Similarly, preclinical studies in rats show that naltrexone and naloxone, another opioid antagonist, decreased sucrose reinforced place preference ( Delamater et al, 2000 ; Agmo et al, 1995 ).…”

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

“…One possibility is that opioid receptors are not crucial for model-free learning required in this task. This is in opposition to previous studies showing that acute administration of naltrexone, comparably to amisulpride, causes a reduction of cue responsivity and reward impulsivity 66 , decreases effort to obtain immediate primary rewards 67 , and decreases the wanting of rewards 70 . Similarly, preclinical studies in rats show that naltrexone and naloxone, another opioid antagonist, decreased sucrose reinforced place preference 71,72 .…”

Multicomponential affective processes modulating food-seeking behaviors

“…By contrast, only the opiodergic manipulation induced a reduction in positive facial expressions in response to liked food rewards during their consumption. These results are in line with other human studies suggesting the involvement of the dopamine system in Pavloviantriggered motivation [20][21][22][23] and the implication of the opioid system in motivational and hedonic processes [24][25][26] (but see [27], for a study suggesting that the opioid system mediates neural connectivity related to motivational, but not hedonic, processes). Furthermore, another recent study [28•] showed that the motivational and hedonic processes involved in the affective response to a reward recruit distinct subregions of the ventral striatum in humans.…”