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Dopaminergic systems create reward seeking despite adverse consequences.

ABSTRACT: Resource-seeking behaviours are ordinarily constrained by physiological needs and threats of danger, and the loss of these controls is associated with pathological reward seeking¹. Although dysfunction of the dopaminergic valuation system of the brain is known to contribute towards unconstrained reward seeking^2,3, the underlying reasons for this behaviour are unclear. Here we describe dopaminergic neural mechanisms that produce reward seeking despite adverse consequences in Drosophila melanogaster. Odours paired with optogenetic activation of a defined subset of reward-encoding dopaminergic neurons become cues that starved flies seek while neglecting food and enduring electric shock punishment. Unconstrained seeking of reward is not observed after learning with sugar or synthetic engagement of other dopaminergic neuron populations. Antagonism between reward-encoding and punishment-encoding dopaminergic neurons accounts for the perseverance of reward seeking despite punishment, whereas synthetic engagement of the reward-encoding dopaminergic neurons also impairs the ordinary need-dependent dopaminergic valuation of available food. Connectome analyses reveal that the population of reward-encoding dopaminergic neurons receives highly heterogeneous input, consistent with parallel representation of diverse rewards, and recordings demonstrate state-specific gating and satiety-related signals. We propose that a similar dopaminergic valuation system dysfunction is likely to contribute to maladaptive seeking of rewards by mammals.

SUBMITTER: Jovanoski KD

PROVIDER: S-EPMC10632144 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Dopaminergic systems create reward seeking despite adverse consequences.

Jovanoski Kristijan D KD Duquenoy Lucille L Mitchell Jessica J Kapoor Ishaan I Treiber Christoph D CD Croset Vincent V Dempsey Georgia G Parepalli Sai S Cognigni Paola P Otto Nils N Felsenberg Johannes J Waddell Scott S

Nature 20231025 7986

Resource-seeking behaviours are ordinarily constrained by physiological needs and threats of danger, and the loss of these controls is associated with pathological reward seeking<sup>1</sup>. Although dysfunction of the dopaminergic valuation system of the brain is known to contribute towards unconstrained reward seeking<sup>2,3</sup>, the underlying reasons for this behaviour are unclear. Here we describe dopaminergic neural mechanisms that produce reward seeking despite adverse consequences in ...[more]

PMID: 37880370

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Dopaminergic systems create reward seeking despite adverse consequences.

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Dopaminergic systems create reward seeking despite adverse consequences.

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