# Molecular Component - Contet

> **NIH NIH P60** · SCRIPPS RESEARCH INSTITUTE, THE · 2021 · $208,982

## Abstract

SUMMARY – Molecular Component
The TSRI-ARC as an integrated whole will focus on the neurobiology of protracted abstinence and its role in
relapse and recovery. The Molecular Component will test the hypothesis that alterations in the composition
and/or dynamics of the microtubule (MT) cytoskeleton contribute to the motivational and emotional
symptomatology of abstinence by driving the structural remodeling of neurons in key brain regions.
The first Specific Aim will be to determine alterations in MT composition and dynamics, using state-of-the-art
proteomics methodology to quantify the abundance of α- and β-tubulin isotypes, MT-associated proteins known
to regulate MT dynamics, and tubulin posttranslational modifications indicative of MT stability. These analyses
will be performed in the medial prefrontal cortex (mPFC), anterior insula, and amygdala. Mice will be exposed to
chronic intermittent ethanol inhalation (CIE) and brains will be collected 1 and 4 weeks into withdrawal to explore
the development and persistence of molecular adaptations in early and late abstinence, respectively. The second
Specific Aim will be to test the functional implication of MT alterations in ethanol drinking escalation, negative
affect and dendritic remodeling during abstinence. A first approach will involve local knockdown of tubulin
isotypes and MT-associated proteins to mimic or reverse abundance changes identified in Specific Aim 1.
Another approach will entail systemic treatment with the synthetic pregnenolone derivative MAP4343 to stimulate
MT dynamics and accelerate recovery from withdrawal. The third Specific Aim will be to complement research
conducted by other TSRI-ARC components. A first experiment will probe the involvement of glucocorticoid
receptor signaling in the effect of CIE on MT dynamics. A second experiment will test the role of serotonergic
projections to the central amygdala and mPFC in the anxiety-like behavior associated with abstinence from CIE.
Altogether, this project is anticipated to identify a molecular mechanism for the homeostatic failure—or
allostasis—that characterizes alcohol use disorders and underlies relapse vulnerability during protracted
abstinence. The Molecular Component will have strong interactions with the Animal Models Core, will involve
collaborations with the Neurophysiology and Neurocircuitry Components, and will provide a mechanistic basis
for the testing of compounds by the Clinical Component.

## Key facts

- **NIH application ID:** 10075855
- **Project number:** 5P60AA006420-38
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Candice Contet
- **Activity code:** P60 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $208,982
- **Award type:** 5
- **Project period:** 1983-12-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10075855

## Citation

> US National Institutes of Health, RePORTER application 10075855, Molecular Component - Contet (5P60AA006420-38). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10075855. Licensed CC0.

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