# Neurobiology of risk taking in females: hormonal modulation of basolateral amygdala function

> **NIH NIH F31** · UNIVERSITY OF TEXAS AT AUSTIN · 2022 · $43,549

## Abstract

Project Summary
Elevated risk taking contributes not only to the development of substance use disorder (SUD) but also the
likelihood of relapse. There has been significant progress in delineating the neural substrates underlying this
causal relationship. Nonetheless, we are still faced with a significant barrier in translating these findings to the
clinical setting because the majority of the work on this topic has used male subjects. This is despite the well-
established sex differences in risk taking and aspects of SUD. This significant limitation in scientific
advancement can be remediated by examining neurobiological mechanisms underlying decision making in
females. The long-term goal of our lab is to identify the neural mechanisms mediating risk taking in females
and how hormones contribute to these processes. To meet this goal, I will use a rodent model of risk taking in
which females are more risk averse and exhibit greater sensitivity to risk of punishment than males. In this model,
female risk aversion is largely mediated by estradiol (E2) and such E2-dependent risk aversion requires estrogen
receptor (ER) β. We have also established a role for the basolateral amygdala (BLA) and its projections to the
nucleus accumbens (NAc) shell in promoting risk averse behavior. Preliminary data reveal that activation of D2
dopamine receptors (D2Rs) in the BLA increases risk aversion in females, but not males. These findings suggest
that differences in BLA function may underlie sex differences in risk taking, and specifically, promote risk aversion
in females. Prior work shows sex differences in BLA-dependent behavior are due to the ability of E2 to modulate
BLA activity and function. Given the role of the BLA in risk taking and the fact it is potently modulated by E2, it is
therefore conceivable that risk aversion in females may be due to E2 regulation of BLA activity necessary for
risk-based decision making. Consequently, the overall objective of this proposal is to dissect the neural
mechanisms by which E2 promotes risk aversion in females. I hypothesize that E2 mediates female risk aversion
through its modulation of ERβ and D2R function in the BLA and its projections to the NAc shell. I will test my
hypothesis by carrying out three experimental aims. In Aim 1, I will identify the contributions of ERs in the BLA
to E2-dependent risk aversion in females using RNA interference-mediated ER gene reduction. In Aim 2, I will
identify the necessity of E2 modulation of D2R function in the BLA for risk aversion in females using optogenetic
manipulation of BLA neurons that selectively express D2Rs. In Aim 3, I will identify the contribution of E2
modulation of BLA projections to the NAc shell to risk aversion in females using optogenetic manipulation of this
circuit. This project is significant because the knowledge gained will advance our understanding of the neural
mechanisms by which E2 mediates female risk aversion and provide a foundation from which we ...

## Key facts

- **NIH application ID:** 10538387
- **Project number:** 1F31DA057112-01
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Leah Marie Truckenbrod
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $43,549
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10538387

## Citation

> US National Institutes of Health, RePORTER application 10538387, Neurobiology of risk taking in females: hormonal modulation of basolateral amygdala function (1F31DA057112-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10538387. Licensed CC0.

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