Date of Completion

2025

Document Type

Honors College Thesis

Department

Department of Psychology and Department of Neuroscience

Thesis Type

College of Arts and Science Honors, Honors College

First Advisor

Donna Toufexis

Keywords

estrogen, sex, extinction, learning, striatum, behavior

Abstract

Operant conditioning involves modifying behavior through reinforcement and punishment, with extinction occurring when a previously reinforced response declines due to the absence of reinforcement. While extinction has been primarily associated with limbic structures such as the hippocampus, amygdala, and infralimbic cortex, emerging evidence implicates the dorsolateral striatum (DLS) of the basal ganglia in both extinction learning and habit formation. The DLS is critical for habit consolidation and behavioral flexibility, with disruptions leading to maladaptive behaviors such as addiction and obsessive-compulsive disorders. Additionally, gonadal hormones, particularly estrogen, modulate fear extinction, with females exhibiting faster extinction rates than males. However, the role of estrogen in male extinction learning remains underexplored. This study investigates the effects of 17β-estradiol (E2) infusion into the DLS on extinction learning in male and female Long Evans rats. Using operant conditioning, we assessed lever-pressing behavior during extinction trials following intra-DLS E2 or vehicle administration. Results revealed a sex-dependent effect: E2 enhanced extinction and extinction memory recall in females while impairing both in males. These findings suggest that estrogen modulates DLS-dependent extinction via sex-specific mechanisms, potentially involving differential dopaminergic receptor activation (D1 vs. D2). The data support a model in which estrogen enhances behavioral flexibility in females by promoting D2-mediated inhibition of the striatal "go" pathway, whereas in males, it may reinforce habitual responding via D1 or ERα activation. These results highlight the DLS as a key locus for hormonal modulation of learning and extinction, with implications for understanding sex differences in neuropsychiatric disorders such as addiction and Parkinson’s disease.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Available for download on Saturday, May 30, 2026

Share

COinS