# A novel role for the medial amygdala in the modulation of sex differences in cocaine reward

> **NIH NIH R00** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $249,000

## Abstract

PROJECT SUMMARY/ABSTRACT
 Sex differences in the propensity to develop substance use disorders (SUD) are well established, but
research to determine the mechanistic underpinnings remains sparse. In recent years, the number of women
with SUD has markedly increased and the number of adolescent girls using stimulants has exceeded that of
boys. Given that females are more sensitive to drugs of abuse, develop SUD more quickly, find it more difficult
to quit once addicted, suffer greater withdrawal symptoms and exhibit shorter times of abstinence before
relapse, this demographic shift in drug taking behaviors represents a public health crisis. Addiction is a
medical, social and economic burden with few treatment options and none that are sex-specific. Therefore, it is
imperative to understand the pathophysiology of addiction and how best to manage it, in men and women. In
my career, I will build an independent research program that investigates and clarifies the cellular, molecular
and circuit specific mechanisms of sex differences in drug addiction. This proposal will investigate the role of
the medial amygdala (meAMY), a known sexually dimorphic region, in modulating sex differences in cocaine
self-administration (SA). This Pathway to Independence Award will provide the opportunity to build on my
expertise in sexual differentiation of the brain and cellular/molecular neuroscience while simultaneously
developing my training in behavioral pharmacology and in vivo imaging and manipulation of circuit activity. In
the mentored (K99) portion of this award, I will focus on characterizing sex differences in meAMY activity and
its modulation of reward through sex-specific inputs to the ventral tegmental area (VTA). Under the mentorship
of Drs. Eric Nestler and Veronica Alvarez, I will investigate how meAMY cellular activity is temporally
associated with sexually dimorphic SA behaviors using fiber photometry to measure in vivo Ca2+ flux. This
cutting-edge and powerful technique can probe meAMY cellular activity in a real-time during acquisition of
cocaine SA, a sexually dimorphic behavior. With additional mentorship from Dr. Paul Kenny, I will study the
functionality of sex differences in connectivity of the meAMY to VTA by chemogenetically inhibiting sex-specific
meAMY – VTA projections in males to reverse/reduce sex difference in SA acquisition. These experiments will
prepare me to functionally interrogate the role of the meAMY as a mediator of sex differences in reward
throughout mesolimbic dopamine pathways in the R00 portion of this award. My independent laboratory will
investigate meAMY sex differences in modulation of glutamatergic inputs to the nucleus accumbens (NAc)
during operant SA and characterize the role of these inputs in sexually dimorphic drug-seeking behaviors. In
sum, the research proposed in this Pathway to Independence Award will reveal both separate and potentially
interactive cellular and circuit-wide mechanisms underlying sex differenc...

## Key facts

- **NIH application ID:** 10117322
- **Project number:** 4R00DA042100-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Deena M. Walker
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2018-05-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10117322

## Citation

> US National Institutes of Health, RePORTER application 10117322, A novel role for the medial amygdala in the modulation of sex differences in cocaine reward (4R00DA042100-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10117322. Licensed CC0.

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