# B1 noradrenergic blockade in early withdrawal to reduce cocaine induced behavioral flexibility deficit

> **NIH NIH R00** · ROWAN UNIVERSITY SCHOOL/OSTEOPATHIC MED · 2022 · $53,188

## Abstract

PROJECT SUMMARY
Balancing habitual and flexible strategies for navigating the environment is necessary for behavior
that is both cognitively efficient yet adaptive to change, and perturbations that disrupt this balance
can result in significant behavioral impairments. For example, patients with substance abuse
disorders often have difficulty altering their behavior to respond to changing outcomes, leading to
poor decision-making. In the rat, a history of cocaine impairs the ability to adjust behavior away
from reward-predictive cues following reward devaluation, a canonical measure of flexible
behavior (i.e., cocaine leads to inflexible behavior). Interestingly, different striatal substrates
underlie flexible, goal-directed behaviors (nucleus accumbens, NAc) and inflexible, habitual
behaviors (dorsal lateral striatum, DLS), and proper balance between the NAc and DLS and their
associated networks is critical for adaptive (flexible) but efficient (habitual) behavior. The parent
award for this diversity supplement examines how a history of cocaine tips that balance and alters
the neural network signaling that drives flexible and inflexible strategies. Balancing these
subcortical networks requires cortical input. Specifically, to determine how distinct mPFC
subregions (prelimbic cortex, PrL; and infralimbic cortex, IL) are differentially involved in flexible
and inflexible strategies, respectively. Here, we will focus on elucidating how a history of cocaine
leads to inflexible behavior and aberrant PrL and IL neural activity. We propose that early stress
during withdrawal contributes to deficits in behavioral flexibility induced by cocaine self-
administration. Corticosterone treatment is sufficient to shift behavior towards inflexible
strategies, similar to what we have reported with a history of cocaine. Since β1 antagonism can
reduce early cocaine withdrawal symptoms such as elevated anxiety and corticosterone, we
hypothesize that this treatment will restore cocaine induced deficits in flexible behavior. This
project will allow for the candidate to learn new techniques (surgeries, self-administration, in vivo
electrophysiological analysis) and prepare for continuing my research career by applying to
graduate school. Understanding the neural circuitry underlying inflexible behavior how neural
encoding in these regions is altered by drug use will provide critical insight into new and more
selective targets for therapeutic intervention for patients with substance abuse disorders.

## Key facts

- **NIH application ID:** 10550086
- **Project number:** 3R00DA042934-05S1
- **Recipient organization:** ROWAN UNIVERSITY SCHOOL/OSTEOPATHIC MED
- **Principal Investigator:** Elizabeth A West
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $53,188
- **Award type:** 3
- **Project period:** 2020-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10550086

## Citation

> US National Institutes of Health, RePORTER application 10550086, B1 noradrenergic blockade in early withdrawal to reduce cocaine induced behavioral flexibility deficit (3R00DA042934-05S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10550086. Licensed CC0.

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