# Neurobiological mechanisms underlying persistent effects of stress on drug-seeking behaviors

> **NIH NIH K00** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $102,336

## Abstract

DESCRIPTION (provided by applicant): Through associative learning processes, cues in the
environment become predictors of biologically relevant stimuli (e.g. food). However, when attributed
with incentive value, such cues can become powerful motivators of maladaptive behavior. For example,
addicts often relapse upon exposure to cues (e.g. people, paraphernalia) previously associated with the
drug-taking experience. Using an animal model that captures individual variation in the propensity to
attribute incentive value to reward cues, we can investigate the neurobiological mechanisms underlying
cue-motivated psychopathologies like addiction. Rats that undergo Pavlovian training, consisting of cue
presentation followed by delivery of a food reward, will often develop either a sign- or goal-tracking
conditioned response. For both sign-trackers (ST) and goal-trackers (GT) the cue attains predictive
value, but for ST the cue also attains incentive value. The attribution of incentive value to the cue
transforms it into a “motivational magnet”, rendering it attractive and desirable for ST, but not GT. It has
been shown that different brain circuits are engaged in response to the cue in ST vs. GT, and that
dopamine (DA) is necessary for incentive (i.e. sign-tracking), but not predictive (i.e. goal-tracking)
learning processes. However, to date, little has been investigated beyond the traditional “motive” circuit
in ST and GT. To expand our knowledge in this regard, I will study the interaction between stress- and
reward-systems in ST and GT rats. DA has long been known to interact with corticosterone (CORT), a
primary mediator of the stress-response, and in turn potentiate motivated behaviors. Given that cue-elicited DA and CORT profiles differ between ST and GT, the overarching hypothesis of my work is that
DA- and CORT-integrative circuits mediate individual differences in the attribution of incentive value to
reward cues. The goal of the proposed work is to identify an intersection between stress- and reward-systems that drives distinct behavioral responses to environmental stimuli. To do so, I will combine and
become proficient with endocrine, neurochemical, pharmacological, genetic, and behavioral
approaches and analyses. This work will elucidate potential mechanisms that may render individuals
more susceptible to cue-driven psychopathologies, and provide comprehensive training towards my
independent scientific growth.

## Key facts

- **NIH application ID:** 10887564
- **Project number:** 5K00DA055493-06
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Sofia A Lopez-Kawa
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $102,336
- **Award type:** 5
- **Project period:** 2019-09-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10887564

## Citation

> US National Institutes of Health, RePORTER application 10887564, Neurobiological mechanisms underlying persistent effects of stress on drug-seeking behaviors (5K00DA055493-06). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10887564. Licensed CC0.

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