"Mechanisms Underlying Estrous Cycle-Dependent Changes in Incubated Coc" by Erin Elizabeth Wannen

Date Approved

6-9-2025

Embargo Period

6-9-2026

Document Type

Dissertation

Degree Name

Ph.D. Neuroscience

Department

Cell Biology and Neuroscience

College

Rowan-Virtua School of Translational Biomedical Engineering & Sciences

Advisor

Daniel Manvich, Ph.D.

Committee Member 1

Jessica Loweth, Ph.D.

Committee Member 2

Elizabeth West, Ph.D.

Committee Member 3

Benjamin Rood, Ph.D.

Committee Member 4

Archana Kumari, Ph.D.

Keywords

BLA;Cocaine;Estrous Cycle;Incubation of Craving;Sex Differences

Disciplines

Medical Sciences | Medicine and Health Sciences | Neurosciences

Abstract

Cues associated with cocaine use are one of the most common relapse triggers and understanding what promotes cue-induced cocaine craving and relapse is a critical question in the field. Human studies have shown that these measures are impacted by fluctuations in ovarian hormone levels, as higher levels of estradiol promote cue-induced cocaine craving in women while higher levels of progesterone reduce craving in both sexes. Enhanced or incubated cue-induced cocaine seeking or craving also changes across the rodent reproductive (estrous) cycle as levels of estradiol and progesterone fluctuate, with enhanced seeking behavior observed during the estrus stage of the cycle. However, how ovarian hormones impact cocaine craving and relapse vulnerability and the molecular underpinnings driving these changes remain unclear. Here we found that administering hormone modulators to block estrogen and progesterone receptors during proestrus, when ovarian hormones are reaching peak levels, does not attenuate the enhanced cue-induced cocaine seeking behavior exhibited during estrus. However, we found that acutely inhibiting estrogen receptors only during estrus does attenuate enhanced cue-induced cocaine seeking behavior, indicating that rapid estrogen receptor signaling may be potentiating this behavior. Further, we found estrous cycle-dependent changes in estrogen receptor and AMPA receptor subunit expression in the basolateral amygdala of cocaine-exposed rats, a region known to mediate incubated cue-induced cocaine seeking. Together, these findings begin to parse apart the role of ovarian hormones in enhanced cue-induced cocaine seeking behavior and identify potential mechanisms underlying these effects.

Available for download on Tuesday, June 09, 2026

Included in

Neurosciences Commons

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