Document Type

Dissertation/Thesis

Date Created

3-29-2021

Embargo Date

3-29-2022

Abstract

Inhalants as environmental contaminants or recreational drugs pose a considerable health concern, but little is known about their mode of action. In 2011, a study from the National Institute for Drug Addiction revealed that an estimate of 21.7 million people aged 12 or older have used inhalants that contain high concentrations of volatile organic compounds, primarily toluene. These compounds can have debilitating impact on brain chemistry. While the impact of toluene on the central dopamine reward pathway has been already reported, the exact mechanism underlining the effect of toluene is still obscure. Towards this goal, the present work seeks to unravel how toluene affects the dopamine system in the nucleus accumbens, a region implicated in addiction. Following the exposure of 63 mice to toluene inhalation for 30 minutes each day on seven consecutive days, slice fast scan cyclic voltammetry (FSCV) with carbon fiber microelectrodes was utilized to measure baseline dopamine release. The impact of toluene on the dopamine neurotransmission was further assessed by examining D2 receptor distribution using immunocytochemistry. Finally, x-ray fluorescence was used to quantify potassium, calcium, iron, copper, and zinc; elements used as secondary messengers in neurons. The combination of the electroanalytical, immunoassays, and spectroscopy shows toluene induced dysregulation in dopamine neurotransmission that could be the result of oxidative damage to neurons in the nucleus accumbens.

Keywords

toluene, inhalation, nucleus accumbens, dopamine, mouse, FSCV

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