Date of Award

9-4-2025

Document Type

Open Access Thesis

Department

Psychology

First Advisor

Peter Vento

Abstract

Addiction involves persistent reward-seeking behavior despite adverse outcomes, with the nucleus accumbens (NAc) critically mediating motivation and cost-benefit decision-making. Dopamine (DA)-responsive neurons in the NAc, specifically D1 and D2 receptors within the NAc are crucial in encoding motivated behavior. However, the specific role of D1/D2 receptors in driving reward-seeking under punishment remains unclear. Preliminary findings suggest a sex-specific effect, with females exhibiting greater sensitivity to the suppressive effects of footshock on natural reward-seeking compared to males. We investigated the differential roles of NAc D1/D2 receptors in modulating reward-seeking behavior under punishment, with a focus on potential sex-specific effects. Using a two-choice punished food-seeking task (progressive punishment paradigm), male and female rats chose between a small, unpunished reward and a larger, punished reward, with footshock intensity increasing alongside the larger reward. We microinfused a D1 agonist (SKF-81297) and D2 agonist (quinpirole) into the NAc and assessed changes in punishment tolerance. In both sexes, SKF-1297 seemed to have a negative effect on reward-seeking behavior, leading to more sensitivity to the shock intensity (punishment sensitivity). However, in males, quinpirole significantly increased the shock intensity tolerated to obtain the larger reward, indicating enhanced reward-seeking under punishment. While this specific effect was not observed in female rats, their behavior showed a significant difference in latency performance when given quinpirole, but not the vehicle control.

This suggests a sex- and- dose-specific modulation of motivated behavior. These findings highlight the role of NAc D2 receptors in promoting persistent reward-seeking despite punishment, specifically in males. The absence of this effect in females underscores a potential neurobiological basis for sex differences in addiction vulnerability. Ongoing studies are testing whether use of both a D1 and D2-like antagonist amplifies these behaviors, shedding light on dopamine’s role in punished reward seeking in the nucleus accumbens.

Rights

© 2025, Anna Caroline Toburen

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