Opioidergic modulation of monetary incentive delay fMRI responses

Samuel Turton; Peter C.T. Hawkins; Christopher Muller-Pollard; Evangelos Zois; Patricia Conrod; Fernando Zelaya; Mitul A. Mehta

doi:10.1007/s00213-025-06753-7

Opioidergic modulation of monetary incentive delay fMRI responses

Samuel Turton^*, Peter C.T. Hawkins, Christopher Muller-Pollard, Evangelos Zois, Patricia Conrod, Fernando Zelaya, Mitul A. Mehta

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Rationale: It is hypothesised that modulation of striatal dopaminergic signalling plays a key role in the rewarding effects of opioids. The monetary incentive delay (MID) task is a functional magnetic resonance imaging (fMRI) paradigm used to investigate striatal responses, which may reflect striatal dopamine release, during the anticipation of a financial reward. Objectives: We hypothesised that fentanyl would modulate striatal MID task Blood Oxygenation Level Dependent (BOLD) responses, reflecting opioidergic modulation of striatal dopaminergic signalling. Methods: 24 right-handed males who undertook four MRI scanning sessions, during which they completed an MID task 15 min after receiving an intravenous infusion of either one of two doses of fentanyl (50 µg/70kg), naloxone (400 µg) or placebo (saline 0.9%), were included in the analyses. End tidal CO₂ data were collected to control for respiratory depression. Results: We demonstrated fentanyl induced increases in MID task reward and loss anticipation BOLD compared with placebo and naloxone in both region of interest (ROI) and whole brain analyses. These results were in cortical regions including the lingual gyrus, precuneus, posterior cingulate and frontal pole rather than the striatum. Conclusions: Our results show the primary effects of fentanyl on MID anticipation BOLD in regions associated with the preparation of a motor response to a salient visual cue, rather than in regions typically associated with reward processing such as the striatum. This suggests that opioid agonists do not affect striatal activation during the MID task. Tasks using naturalistic rewards, for example feeding, sex or social contact which induce endogenous opioid signalling, may be more appropriate to probe the effects of fentanyl on reward processing. These results are from male participants’ data and therefore may not be generalisable to female participants.

Original language	English
Journal	Psychopharmacology
DOIs	https://doi.org/10.1007/s00213-025-06753-7
Publication status	Accepted/In press - 2025

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10.1007/s00213-025-06753-7

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@article{0bef638add50459b9166eb2d3ac41782,

title = "Opioidergic modulation of monetary incentive delay fMRI responses",

abstract = "Rationale: It is hypothesised that modulation of striatal dopaminergic signalling plays a key role in the rewarding effects of opioids. The monetary incentive delay (MID) task is a functional magnetic resonance imaging (fMRI) paradigm used to investigate striatal responses, which may reflect striatal dopamine release, during the anticipation of a financial reward. Objectives: We hypothesised that fentanyl would modulate striatal MID task Blood Oxygenation Level Dependent (BOLD) responses, reflecting opioidergic modulation of striatal dopaminergic signalling. Methods: 24 right-handed males who undertook four MRI scanning sessions, during which they completed an MID task 15 min after receiving an intravenous infusion of either one of two doses of fentanyl (50 µg/70kg), naloxone (400 µg) or placebo (saline 0.9%), were included in the analyses. End tidal CO2 data were collected to control for respiratory depression. Results: We demonstrated fentanyl induced increases in MID task reward and loss anticipation BOLD compared with placebo and naloxone in both region of interest (ROI) and whole brain analyses. These results were in cortical regions including the lingual gyrus, precuneus, posterior cingulate and frontal pole rather than the striatum. Conclusions: Our results show the primary effects of fentanyl on MID anticipation BOLD in regions associated with the preparation of a motor response to a salient visual cue, rather than in regions typically associated with reward processing such as the striatum. This suggests that opioid agonists do not affect striatal activation during the MID task. Tasks using naturalistic rewards, for example feeding, sex or social contact which induce endogenous opioid signalling, may be more appropriate to probe the effects of fentanyl on reward processing. These results are from male participants{\textquoteright} data and therefore may not be generalisable to female participants.",

author = "Samuel Turton and Hawkins, {Peter C.T.} and Christopher Muller-Pollard and Evangelos Zois and Patricia Conrod and Fernando Zelaya and Mehta, {Mitul A.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

doi = "10.1007/s00213-025-06753-7",

language = "English",

journal = "Psychopharmacology",

issn = "0033-3158",

publisher = "Springer Verlag",

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T1 - Opioidergic modulation of monetary incentive delay fMRI responses

AU - Turton, Samuel

AU - Hawkins, Peter C.T.

AU - Muller-Pollard, Christopher

AU - Zois, Evangelos

AU - Conrod, Patricia

AU - Zelaya, Fernando

AU - Mehta, Mitul A.

PY - 2025

Y1 - 2025

N2 - Rationale: It is hypothesised that modulation of striatal dopaminergic signalling plays a key role in the rewarding effects of opioids. The monetary incentive delay (MID) task is a functional magnetic resonance imaging (fMRI) paradigm used to investigate striatal responses, which may reflect striatal dopamine release, during the anticipation of a financial reward. Objectives: We hypothesised that fentanyl would modulate striatal MID task Blood Oxygenation Level Dependent (BOLD) responses, reflecting opioidergic modulation of striatal dopaminergic signalling. Methods: 24 right-handed males who undertook four MRI scanning sessions, during which they completed an MID task 15 min after receiving an intravenous infusion of either one of two doses of fentanyl (50 µg/70kg), naloxone (400 µg) or placebo (saline 0.9%), were included in the analyses. End tidal CO2 data were collected to control for respiratory depression. Results: We demonstrated fentanyl induced increases in MID task reward and loss anticipation BOLD compared with placebo and naloxone in both region of interest (ROI) and whole brain analyses. These results were in cortical regions including the lingual gyrus, precuneus, posterior cingulate and frontal pole rather than the striatum. Conclusions: Our results show the primary effects of fentanyl on MID anticipation BOLD in regions associated with the preparation of a motor response to a salient visual cue, rather than in regions typically associated with reward processing such as the striatum. This suggests that opioid agonists do not affect striatal activation during the MID task. Tasks using naturalistic rewards, for example feeding, sex or social contact which induce endogenous opioid signalling, may be more appropriate to probe the effects of fentanyl on reward processing. These results are from male participants’ data and therefore may not be generalisable to female participants.

AB - Rationale: It is hypothesised that modulation of striatal dopaminergic signalling plays a key role in the rewarding effects of opioids. The monetary incentive delay (MID) task is a functional magnetic resonance imaging (fMRI) paradigm used to investigate striatal responses, which may reflect striatal dopamine release, during the anticipation of a financial reward. Objectives: We hypothesised that fentanyl would modulate striatal MID task Blood Oxygenation Level Dependent (BOLD) responses, reflecting opioidergic modulation of striatal dopaminergic signalling. Methods: 24 right-handed males who undertook four MRI scanning sessions, during which they completed an MID task 15 min after receiving an intravenous infusion of either one of two doses of fentanyl (50 µg/70kg), naloxone (400 µg) or placebo (saline 0.9%), were included in the analyses. End tidal CO2 data were collected to control for respiratory depression. Results: We demonstrated fentanyl induced increases in MID task reward and loss anticipation BOLD compared with placebo and naloxone in both region of interest (ROI) and whole brain analyses. These results were in cortical regions including the lingual gyrus, precuneus, posterior cingulate and frontal pole rather than the striatum. Conclusions: Our results show the primary effects of fentanyl on MID anticipation BOLD in regions associated with the preparation of a motor response to a salient visual cue, rather than in regions typically associated with reward processing such as the striatum. This suggests that opioid agonists do not affect striatal activation during the MID task. Tasks using naturalistic rewards, for example feeding, sex or social contact which induce endogenous opioid signalling, may be more appropriate to probe the effects of fentanyl on reward processing. These results are from male participants’ data and therefore may not be generalisable to female participants.

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U2 - 10.1007/s00213-025-06753-7

DO - 10.1007/s00213-025-06753-7

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AN - SCOPUS:86000801334

SN - 0033-3158

JO - Psychopharmacology

JF - Psychopharmacology

ER -

Opioidergic modulation of monetary incentive delay fMRI responses

Abstract

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