Date of Award

8-2024

Document Type

Thesis

Degree Name

Master of Arts in Psychological Science

Department

Psychology

First Reader/Committee Chair

Amodeo, Dionisio

Abstract

The focus on serotonergic dysfunction as a contributor to cognitive deficits in disorders such as autism spectrum disorder, Alzheimer's disease, and schizophrenia drives researchers to investigate the functional impact of specific serotonin receptor types on executive functioning. By discerning the potential enhancement or impairment effects, this endeavor seeks to unravel the complex interplay between serotonin receptors and cognitive abilities. Specifically, within the three domains of learning, acquisition, consolidation, and retrieval, we find serotonergic modulation to be pivotal. Recent studies have highlighted the 5-HT6 receptor as a novel target for cognitive enhancement. However, the majority of the research investigates the effects of 5-HT6 receptor blockade on executive functioning, leaving many unanswered questions on how 5-HT6 activation affects cognition. The current study aims to address these gaps within the literature by examining the effects of the 5-HT6 agonist EMD 386088 on the consolidation of learning. Specifically, we aim to examine how 5-HT6 receptor agonism impacts the consolidation of a probabilistic spatial discrimination task. To do so, male and female C57BL/6J mice were tested in a spatial probabilistic learning paradigm, and received systemic injections of either 0, 1, or 5 mg/kg EMD386088 treatment immediately after task training, 24 hours before retention testing, to target distinct consolidation phases of learning. During the retention test, both doses of 1 mg/kg and 5 mg/kg significantly impaired the performance of male and female mice. Although there were no significant differences between the two doses, mice treated with EMD386088 required significantly more trials to reach retention criterion compared to vehicle-treated mice. Female mice treated with 1 mg/kg EMD386088 made significantly more regressive errors showing a significant impairment in their ability to maintain a new choice pattern after shifting to the correct choice. These learning impairments were independent of effects on locomotor activity due to the comparable duration of trial completion across all treatment groups during both the acquisition and retention testing. The current findings demonstrate the potential sensitivity of treatment timing in the application of novel therapeutics aimed at stimulating 5-HT6 receptors and their impact on cognitive outcomes.

Download

  Contact Author

Share

COinS