# Effect of Toluene on the Prefrontal-Amygdala Pathway and Risky Behavior

> **NIH NIH F31** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $15,873

## Abstract

NRSA F31 APPLICATION
“Effect of Toluene on the Prefrontal-Amygdala Pathway and Risky Behavior”
PI: Kevin M. Braunscheidel
Sponsor: John J. Woodward
ABSTRACT
Volatile organic solvents like toluene cause intoxication and neurochemical alterations when inhaled at high
concentrations. These include electrophysiological and morphological changes in cortical (e.g. medial prefrontal
cortex, mPFC) and subcortical regions common among many addictive substances. As revealed by our lab, ex
vivo application of toluene causes a persistent depression of excitatory signaling in the mPFC that is dependent
on endocannabinoids. The behavioral consequences of this action are not currently known, but it is possibly
responsible for the loss of executive control over complex behaviors such as decision making in the face of risky
outcomes. Aim 1 of this proposal will measure the effect of acute toluene intoxication on risky decision making
in rodents using a semi-automated task termed probabilistic discounting. Appropriate responding in this task
depends on functional connectivity between the mPFC and the basolateral amygdala (BLA). The BLA is
traditionally viewed as mediating fear-related behaviors, but also clearly plays a role in addiction to abused
substances including cocaine and alcohol. Virtually nothing is known about the role of the BLA in solvent-induced
disruption of risky decision making and studies in this proposal will use in vivo fiber photometry combined with
targeted viral delivery of calcium sensing GCaMP6 to determine which specific components of this task depend
on mPFC-BLA connectivity. To provide the first characterization of the cellular actions of solvents on BLA neuron
excitability, studies in Aim 2 will use whole-cell patch clamp brain slice electrophysiology to measure the effect
of toluene on the intrinsic excitability of BLA neurons. The effects of toluene on mPFC-specific synaptic
transmission will be assessed by optogenetically activating mPFC terminals and recording glutamatergic post-
synaptic currents in voltage clamped BLA neurons. Follow up studies will use optical plasticity protocols to
determine how toluene alters the ability of BLA neurons to modify synaptic strength. Completing these aims will
provide outstanding training in behavioral pharmacology, fiber photometry, and slice electrophysiology and will
address an important shortcoming in our understanding of the mechanisms underlying toluene’s effect on
complex behaviors.

## Key facts

- **NIH application ID:** 9899236
- **Project number:** 5F31DA045485-03
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Kevin Braunscheidel
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $15,873
- **Award type:** 5
- **Project period:** 2018-04-01 → 2020-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899236

## Citation

> US National Institutes of Health, RePORTER application 9899236, Effect of Toluene on the Prefrontal-Amygdala Pathway and Risky Behavior (5F31DA045485-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9899236. Licensed CC0.

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