Date of Award

Summer 2025

Document Type

Open Access Thesis

Department

Psychology

First Advisor

Peter Vento

Abstract

The role of midbrain dopamine (DA) activity in reward seeking and reinforcement learning is well-documented, contrasting the lesser-understood impact of inhibitory signaling on DAergic activity, especially in the context of aversive learning and avoidance. The rostromedial tegmental nucleus (RMTg) is a GABAergic midbrain structure activated by aversive stimuli and exerts inhibitory influence over ventral tegmental area (VTA) DAergic activity in response to aversive consequences. Stimulation of the RMTg decreases the firing rate of VTA DA neurons and direct inhibition of the RMTg – VTA circuit enhances persistent reward seeking despite aversive consequences, a major criterion of substance use disorder (SUD). Yet, it remains unknown what effect RMTg – VTA stimulation, in the absence of an overtly aversive stimulus, may have on inducing an avoidance toward a previously desired food reward. This study examines the effects of stimulating the RMTg – VTA pathway on avoidance behaviors using pathway-specific chemogenetic and optogenetic strategies in a two-flavor choice task where rats are given the option to choose between two flavored food rewards (vanilla- and chocolate-flavored pellets) and whichever flavor is chosen most is deemed the “preferred” flavor and paired with RMTg – VTA stimulation to investigate if stimulation can induce an avoidance toward their preferred flavor. Our chemogenetic approach was designed to condition an avoidance over time via alternating CNO- and vehicle-paired sessions where only one flavor option is allowed per session. Chemogenetic activation of the RMTg – VTA circuit was sufficient to condition an avoidance toward the preferred flavor, however, rats showed a gradual increase toward equal flavor preference by the end of testing. Our optogenetic approach aimed to induce a real-time progressive avoidance toward the preferred flavor via temporally specific stimulation only upon pressing for the preferred flavor. Optical stimulation of the RMTg – VTA pathway resulted in a progressive avoidance of the preferred flavor across light sessions that persisted throughout the entirety of testing. These data suggest an important role for the RMTg – VTA pathway in the expression of avoidance behaviors as well as alterations in decision-making and choice with exciting implications for future interventions aimed at promoting adaptive decision-making and resistance toward drug use.

Rights

© 2025, Jacob Ryan Watson

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