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Dopaminergic modulation of sensitivity to immediate and delayed punishment during decision-making

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Abstract

Effective decision-making involves careful consideration of all rewarding and aversive outcomes. Importantly, negative outcomes often occur later in time, leading to underestimation, or “discounting,” of these consequences. Despite the frequent occurrence of delayed outcomes, little is known about the neurobiology underlying sensitivity to delayed punishment during decision-making. The Delayed Punishment Decision-making Task (DPDT) addresses this by assessing sensitivity to delayed versus immediate punishment in rats. Rats initially avoid punished reinforcers, then select this option more frequently when delay precedes punishment. We used DPDT to examine effects of acute systemic administration of catecholaminergic drugs on sensitivity to delayed punishment in male and female adult rats. Cocaine did not affect choice of rewards with immediate punishment but caused a dose-dependent reduction in choice of delayed punishment. Neither activation nor blockade of D1-like dopamine receptor affected decision-making, but activation of D2-like dopamine receptors reduced choice of delayed punishment. D2 blockade did not attenuate cocaine’s effects on decision-making, suggesting that cocaine’s effects are not dependent on D2 receptor activation. Increasing synaptic norepinephrine via atomoxetine also reduced choice of delayed (but not immediate) punishment. Notably, when DPDT was modified from ascending to descending pre-punishment delays, these drugs did not affect choice of delayed or immediate punishment, although high-dose quinpirole impaired behavioral flexibility. In summary, sensitivity to delayed punishment is regulated by both dopamine and norepinephrine transmission in task-specific fashion. Understanding the neurochemical modulation of decision-making with delayed punishment is a critical step toward treating disorders characterized by aberrant sensitivity to negative consequences.

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Abbreviations

DPDT:

Delayed Punishment Decision-making Task

SUD:

Substance Use Disorder

ANOVA:

Analysis of Variance

IP:

Intraperitoneal

OFC:

Orbitofrontal Cortex

PFC:

Prefrontal Cortex

BLA:

Basolateral Amygdala

NAcc:

Nucleus Accumbens

ITI:

Intertrial Interval

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Acknowledgments

The authors thank Dr. Daniel Gabriel, Tiya Qualls, Boula Baskhairoun, Zachary Mikkelson, Sharoderick Lowe, Jason Leonidas Martinez, and Kayrine Cortes for technical assistance.

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  1. Department of Psychology, University of Memphis, Memphis, TN, USA

    Grace L. Minnes, Anna J. Wiener, Anna E. Liley & Nicholas W. Simon

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  1. Grace L. Minnes
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Correspondence to Nicholas W. Simon.

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None of the experiments or analyses reported here were pre-registered. All raw data, behavioral protocols, and Matlab script are available upon request.

This work was supported by R15DA046797 (NWS). The authors have no conflicts of interest to disclose.

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Minnes, G.L., Wiener, A.J., Liley, A.E. et al. Dopaminergic modulation of sensitivity to immediate and delayed punishment during decision-making. Cogn Affect Behav Neurosci 24, 304–321 (2024). https://doi.org/10.3758/s13415-023-01139-8

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