# Corticolimbic circuitry in adaptive stress coping behavior and subsequent alcohol drinking

> **NIH NIH K99** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $101,519

## Abstract

Project Summary
Individuals with post-traumatic stress disorder (PTSD) consume alcohol as an attempt to alleviate symptoms,
which can increase the risk of developing a drinking problem. However, well-adapted coping responses to stress
may protect against development of PTSD and mitigate subsequent alcohol use. Further, not only are women
twice as likely as men to suffer from PTSD, but certain individuals may be more susceptible or resilient in
adapting to stressful events. This suggests specific brain mechanisms that mediate sex differences in response
to stress and also individual differences in coping responses may mitigate against lasting consequences of stress
such as alcohol consumption. In this proposal, I will investigate how failure to engage in adaptive coping
strategies to stress may be driven by hypofunctioning between corticolimbic regions specifically the prelimbic
(PrL) cortex and the basolateral amygdala (BLA), and whether increases in endocannabinoid signaling can
restore this maladaptive behavior. I utilize an animal model of stress exposure to the predator odor TMT, which
produces distinct coping behaviors between male and female rats, as well as individual differences in subsequent
increases in alcohol self-administration. Using this model, I will utilize a variety of chemogenetic,
electrophysiological and optogenetic techniques to directly manipulate the PrLBLA circuit and examine its
functional role in driving adaptive responses to stress and alcohol self-administration in male and female rats.
Further, I will investigate the direct role of endocannabinoid signaling in modulating maladaptive versus adaptive
coping responses and whether this signaling can act as a protective mechanism against later escalations in
alcohol self-administration. The K99 portion of this proposal involves extensive training using chemogenetic and
cell-specific molecular approaches and advanced electrophysiological techniques to probe both functional
changes and in vivo neuroadaptive responses. This training will provide me with a stronger neuroscience
foundation which will be critical to increase my competitiveness on the job market and will be important in my
independent career. Uncovering the neural mechanisms that drive maladaptive coping behavior and subsequent
alcohol self-administration within the K99 portion will provide future directions for the R00 phase. Studies within
the R00 phase will specifically assess whether endocannabinoids can directly restore PrL hypofunctioning that
leads to dysregulated neuroadaptations within the BLA and central amygdala (CeA) circuitry that drives
behavioral outcomes to stress. Together, completion of these aims will establish corticolimbic circuitry and
endocannabinoid mechanisms that drive coping strategies during predator odor stress and alcohol drinking.
Additionally, studies in this application will further my long-term research goal which is to elucidate
neurobiological mechanisms that underlie sex dif...

## Key facts

- **NIH application ID:** 10519387
- **Project number:** 1K99AA029730-01A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Laura C. Ornelas
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $101,519
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10519387

## Citation

> US National Institutes of Health, RePORTER application 10519387, Corticolimbic circuitry in adaptive stress coping behavior and subsequent alcohol drinking (1K99AA029730-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10519387. Licensed CC0.

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