# CNS Effects of Alcohol: Cellular Neurobiology

> **NIH NIH P60** · SCRIPPS RESEARCH INSTITUTE, THE · 2023 · $1,834,175

## Abstract

Abstract Overall
The Scripps Research Institute-Alcohol Research Center (TSRI-ARC) will focus on the cellular and molecular
mechanisms that modulate top-down medial prefrontal control of the central amygdala and underlie stress-
induced vulnerability to relapse and excessive drinking during protracted abstinence. Our approach consists of
coordinated interdisciplinary molecular, neuroproteomic, cellular, neurocircuitry, connectomic,
neuropharmacological, and behavioral methods. Specific hypotheses are: (1) Protracted abstinence involves
increased vulnerability to stress-induced relapse via changes in modulatory control circuitry from the infralimbic
cortex to the central nucleus of the amygdala. (2) Modulatory control changes are a function of altered
glutamatergic and γ-aminobutyric acid synaptic transmission, due to actions of stress-related molecules
(including hypocretin, corticotropin-releasing factor, dynorphin, and nociceptin) and astrocytic dysfunction. (3)
These neurocircuitry changes are associated with altered connectivity and decreased modularity of brain
networks, leading to increased vulnerability to stress-induced relapse. (4) Novel translationally relevant ligands
of neurobiological targets identified by TSRI-ARC will attenuate the reinstatement of stress-induced alcohol
seeking, excessive drinking, and stress-related behaviors in animal models. Our Center-wide aims will be met
by 5 Research Components (Functional Connectomics, Neuropharmacology, Molecular, Neurophysiology, and
Neurocircuitry), and 4 Cores (Administrative, Dissemination, Animal Models, and Neuroproteomics). The
Administrative Core is organized to optimize Center-wide functioning, utilization of Core resources, and research
collaborations in the Center-at-Large. TSRI-ARC is structured to promote Diversity, Equity, and Inclusion (DEI),
training and career development at all levels of the Center. TSRI-ARC rapidly disseminates its discoveries to
scientific, healthcare and lay stakeholders, and engages young people from health disparity backgrounds for
internships in TSRI-ARC laboratories to learn about alcohol and careers in alcohol research. Center-wide
Specific Aims are: (1) To characterize the cellular and molecular mechanisms that modulate top-down medial
prefrontal control of the central amygdala and underlie stress-induced vulnerability to relapse and excessive
drinking during protracted abstinence. (2) To understand how reversal of the cellular and molecular stress
mechanisms that impair modulatory control systems can prevent stress-induced relapse and excessive drinking
during protracted abstinence. (3) To evaluate the efficacy of neuropharmacological targets identified by TSRI-
ARC for reversing dysregulated connectivity within and between brain stress systems and modulatory control
circuits in protracted abstinence. The ultimate goal of TSRI-ARC is to positively influence public health by
generating data relevant to the identification of neurobiological mecha...

## Key facts

- **NIH application ID:** 10526260
- **Project number:** 2P60AA006420-40
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** BARBARA J MASON
- **Activity code:** P60 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,834,175
- **Award type:** 2
- **Project period:** 1983-12-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10526260

## Citation

> US National Institutes of Health, RePORTER application 10526260, CNS Effects of Alcohol: Cellular Neurobiology (2P60AA006420-40). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10526260. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*