Dopamine activity encodes the changing valence of the same stimulus in conditioned taste aversion paradigms

Mesolimbic dopamine encoding of non-contingent rewards and reward-predictive cues has been well established. Considerable debate remains over how mesolimbic dopamine responds to aversion and in the context of aversive conditioning. Inconsistencies may arise from the use of aversive stimuli that are...

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Main Authors: Maxine K Loh, Samantha J Hurh, Paula Bazzino, Rachel M Donka, Alexandra T Keinath, Jamie D Roitman, Mitchell F Roitman
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2025-03-01
Series:eLife
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Online Access:https://elifesciences.org/articles/103260
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author Maxine K Loh
Samantha J Hurh
Paula Bazzino
Rachel M Donka
Alexandra T Keinath
Jamie D Roitman
Mitchell F Roitman
author_facet Maxine K Loh
Samantha J Hurh
Paula Bazzino
Rachel M Donka
Alexandra T Keinath
Jamie D Roitman
Mitchell F Roitman
author_sort Maxine K Loh
collection DOAJ
description Mesolimbic dopamine encoding of non-contingent rewards and reward-predictive cues has been well established. Considerable debate remains over how mesolimbic dopamine responds to aversion and in the context of aversive conditioning. Inconsistencies may arise from the use of aversive stimuli that are transduced along different neural paths relative to reward or the conflation of responses to avoidance and aversion. Here, we made intraoral infusions of sucrose and measured how dopamine and behavioral responses varied to the changing valence of sucrose. Pairing intraoral sucrose with malaise via injection of lithium chloride (LiCl) caused the development of a conditioned taste aversion (CTA), which rendered the typically rewarding taste of sucrose aversive upon subsequent re-exposure. Following CTA formation, intraoral sucrose suppressed the activity of ventral tegmental area dopamine neurons (VTADA) and nucleus accumbens (NAc) dopamine release. This pattern of dopamine signaling after CTA is similar to intraoral infusions of innately aversive quinine and contrasts with responses to sucrose when it was novel or not paired with LiCl. Dopamine responses were negatively correlated with behavioral reactivity to intraoral sucrose and predicted home cage sucrose preference. Further, dopamine responses scaled with the strength of the CTA, which was increased by repeated LiCl pairings and weakened through extinction. Thus, the findings demonstrate differential dopamine encoding of the same taste stimulus according to its valence, which is aligned to distinct behavioral responses.
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spelling doaj-art-c37f567d4f9a431dae1f08058a0e67342025-08-20T02:46:43ZengeLife Sciences Publications LtdeLife2050-084X2025-03-011310.7554/eLife.103260Dopamine activity encodes the changing valence of the same stimulus in conditioned taste aversion paradigmsMaxine K Loh0https://orcid.org/0000-0002-2933-2768Samantha J Hurh1Paula Bazzino2Rachel M Donka3Alexandra T Keinath4Jamie D Roitman5Mitchell F Roitman6https://orcid.org/0000-0003-3973-635XDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, United States; Department of Psychology, University of Illinois at Chicago, Chicago, United StatesDepartment of Psychology, University of Illinois at Chicago, Chicago, United StatesGraduate Program in Neuroscience, University of Illinois at Chicago, Chicago, United StatesDepartment of Psychology, University of Illinois at Chicago, Chicago, United StatesDepartment of Psychology, University of Illinois at Chicago, Chicago, United StatesDepartment of Psychology, University of Illinois at Chicago, Chicago, United States; Graduate Program in Neuroscience, University of Illinois at Chicago, Chicago, United StatesDepartment of Psychology, University of Illinois at Chicago, Chicago, United States; Graduate Program in Neuroscience, University of Illinois at Chicago, Chicago, United StatesMesolimbic dopamine encoding of non-contingent rewards and reward-predictive cues has been well established. Considerable debate remains over how mesolimbic dopamine responds to aversion and in the context of aversive conditioning. Inconsistencies may arise from the use of aversive stimuli that are transduced along different neural paths relative to reward or the conflation of responses to avoidance and aversion. Here, we made intraoral infusions of sucrose and measured how dopamine and behavioral responses varied to the changing valence of sucrose. Pairing intraoral sucrose with malaise via injection of lithium chloride (LiCl) caused the development of a conditioned taste aversion (CTA), which rendered the typically rewarding taste of sucrose aversive upon subsequent re-exposure. Following CTA formation, intraoral sucrose suppressed the activity of ventral tegmental area dopamine neurons (VTADA) and nucleus accumbens (NAc) dopamine release. This pattern of dopamine signaling after CTA is similar to intraoral infusions of innately aversive quinine and contrasts with responses to sucrose when it was novel or not paired with LiCl. Dopamine responses were negatively correlated with behavioral reactivity to intraoral sucrose and predicted home cage sucrose preference. Further, dopamine responses scaled with the strength of the CTA, which was increased by repeated LiCl pairings and weakened through extinction. Thus, the findings demonstrate differential dopamine encoding of the same taste stimulus according to its valence, which is aligned to distinct behavioral responses.https://elifesciences.org/articles/103260ventral tegmental areanucleus accumbensrewardaversionmotivationreinforcement
spellingShingle Maxine K Loh
Samantha J Hurh
Paula Bazzino
Rachel M Donka
Alexandra T Keinath
Jamie D Roitman
Mitchell F Roitman
Dopamine activity encodes the changing valence of the same stimulus in conditioned taste aversion paradigms
eLife
ventral tegmental area
nucleus accumbens
reward
aversion
motivation
reinforcement
title Dopamine activity encodes the changing valence of the same stimulus in conditioned taste aversion paradigms
title_full Dopamine activity encodes the changing valence of the same stimulus in conditioned taste aversion paradigms
title_fullStr Dopamine activity encodes the changing valence of the same stimulus in conditioned taste aversion paradigms
title_full_unstemmed Dopamine activity encodes the changing valence of the same stimulus in conditioned taste aversion paradigms
title_short Dopamine activity encodes the changing valence of the same stimulus in conditioned taste aversion paradigms
title_sort dopamine activity encodes the changing valence of the same stimulus in conditioned taste aversion paradigms
topic ventral tegmental area
nucleus accumbens
reward
aversion
motivation
reinforcement
url https://elifesciences.org/articles/103260
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