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Access Type
WSU Access
Date of Award
January 2023
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Psychology
First Advisor
Scott E. Bowen
Abstract
Inhalant abuse is a pernicious problem with serious pathological and neurobehavioral consequences, even after brief exposure. The aromatic hydrocarbon, toluene, is one of the most widely abuse inhalants and is present in many conveniently accessed household and commercial products. Toluene’s pharmacological profile is similar to that of ethanol’s, making it an attractive alternative to ethanol. Like ethanol, toluene has been shown to cause serious withdrawal effects following repeated use of binge concentrations. Previous work from our lab showed that toluene can cause anxiogenic-like effects after a prolonged exposure to toluene at abuse-like concentrations. The present dissertation experiment aimed to further explore these effects by assessing the involvement of GABA, as well as the active circuits in the BLA and CeA of the amygdala. This experiment used adolescent male and female Swiss-Webster mice (N = 96) exposed to either air (0 ppm) or toluene (5000 ppm) in a 27-L glass jar for 30 min/2x daily for 4 d. Twenty-four hours following the final exposure, animals were given either saline, muscimol, or bicuculline followed by a sham air exposure. During exposure, animals were tested for locomotor activity (LMA). Immediately following the sham exposure, animals were tested on the elevated plus maze (EPM) followed by the marble burying test (MBT). Following the testing period, animals were euthanized for assessment of c-Fos in the amygdala. Results showed that toluene exposure induced an initial elevation in LMA followed by a decrease throughout the week and a return to control levels at the end of the week. On testing day, toluene-abstinence induced elevations in closed arm time and decreases in open arm time on the elevated plus maze in male mice, but not in females. Muscimol restored these male mice to control levels, suggesting a remedial effect. Interestingly, bicuculline showed a partial reversal of toluene’s anxiogenic-like effects. No changes in burying behavior were observed in the MBT. Follow-up analyses with immunofluorescence showed that toluene produced alterations in amygdalar activity (i.e., changes in c-Fos expression). However, the interaction effects within each subdomain were only trending. This research presents the first of its kind showing GABAergic involvement in toluene-induced anxiogenesis following a translationally relevant exposure schedule. This work has clinical utility and may help to further identify and treat toluene dependence by suggesting possible pharmacotherapies similar to those of ethanol-treatment.
Recommended Citation
Svenson, D. W., "Gabaergic Mediation Of Abstinence-Induced Anxiety Following Repeated Binge-Pattern Toluene Exposure In A Murine Model" (2023). Wayne State University Dissertations. 3894.
https://digitalcommons.wayne.edu/oa_dissertations/3894