Psychology ETDs

Publication Date

Spring 3-14-2024

Abstract

Studies have demonstrated alcohol-related deficits in LTP associated with histaminergic and glutamatergic impairments. The histaminergic H3R inverse agonist ABT-239 has shown promise in reversing these deficits. The present study focuses on another H3R inverse agonist, SAR-152594, and its impact on LTP deficits following moderate PAE. The findings reveal that systemic administration of 1 mg/kg of SAR-152594 reverses deficits in potentiation fEPSPs in adult male rats exposed to moderate PAE. Time-frequency analyses of evoked responses indicate PAE-related reductions in power during the fEPSP and increased power during later components of evoked responses, both reversed by SAR-152594. These results provide further evidence that H3R inverse agonism is a potential therapeutic strategy to address deficits in synaptic plasticity associated with PAE. This study also investigated extracellular glutamate levels with a glutamate biosensor in vivo. Following HFS stimulation, the results show differences in fractional change in amplitude of the evoked responses in PAE animals when compared with controls. These results support the alcohol-related deficits in LTP and support the hypothesis that there is a disruption in glutamate release from the presynaptic terminal.

Degree Name

Psychology

Level of Degree

Doctoral

Department Name

Psychology

First Committee Member (Chair)

Derek Hamilton

Second Committee Member

Benjamin Clark

Third Committee Member

Jeremy Hogeveen

Fourth Committee Member

Daniel Savage

Language

English

Keywords

FASD, synaptic plasticity, glutamate, histamine, electrophysiology, memory

Document Type

Dissertation

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