# Early life stress and adolescent cocaine abuse: neurobiological vulnerabilities

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $169,473

## Abstract

Abstract
Adolescence is a period of increased vulnerability for the development of substance abuse, including cocaine
addiction. Despite the known risk of adolescence initiation of cocaine abuse for lifelong addiction, and its
tremendous health and societal costs in the US, the neurobiological mechanisms of increased risk during this
developmental period are poorly understood. The proposed studies will examine this question in a novel and
highly translational adolescent nonhuman primate model, investigating the effect of an important
risk/vulnerability factor: exposure to early life stress. We will also determine whether increased
emotional/stress reactivity increases vulnerability to cocaine addiction, including relapse, in females.
We will use a highly translational macaque model of early life stress (infant maltreatment) to examine the
neurobiological mechanisms underlying increased vulnerability to cocaine abuse and relapse during
adolescence. The project will build on ongoing longitudinal studies of developmental alterations exhibited by
the maltreated animals, which have been characterized by our group since birth using a unique cross fostering
design that rules out confounding effects of heritability on outcome measures. We have evidence that the
adverse experience leads to increased emotional reactivity and alterations of prefrontal connectivity (both
structural and functional) during the infant period, and we will now examine whether these alterations (1)
persist during adolescence and (2) underlie increased risk to cocaine abuse.
Our goal is to investigate the neurobiological mechanisms underlying increased vulnerability to cocaine abuse
during adolescence in animals with a well-documented history of early life stress, with a particular focus on
alterations in the dopaminergic and serotonergic systems and prefrontal connectivity with the striatum and
amygdala. We hypothesize that the increased emotional reactivity/anxiety characteristic of maltreated animals
exacerbates cocaine self-administration and reinstatement, and that females will be more vulnerable than
males. The study will also test a pharmacological intervention, through the use of pharmacological blockade of
the 5HT2A receptor during cocaine abstinence to reduce the risk of relapse. A critical aspect of this proposal is
its focus on adolescence, as it is the developmental period when humans initiate drug consumption and has
been rarely examined in nonhuman primate studies of cocaine abuse.

## Key facts

- **NIH application ID:** 10084525
- **Project number:** 3R01DA038588-05S1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** MAR M SANCHEZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $169,473
- **Award type:** 3
- **Project period:** 2014-09-30 → 2020-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10084525

## Citation

> US National Institutes of Health, RePORTER application 10084525, Early life stress and adolescent cocaine abuse: neurobiological vulnerabilities (3R01DA038588-05S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10084525. Licensed CC0.

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