# Molecular rhythms and substance abuse vulnerability in adolescents

> **NIH NIH P50** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $299,592

## Abstract

PROJECT SUMMARY
Substance use disorder (SUD) remains a large problem in the United States. The primary goal of the CARRS
Center is to understand how sleep and circadian rhythm traits and environmental disruptions during adolescence
lead to increased vulnerability for substance abuse. We predict that a combination of biological and
environmental factors contribute to this increased risk. The goal of Project 3 in the Center is to provide
translational studies in both human subjects and rodent models that determine mechanistic details of how
circadian rhythm and sleep disruption alter reward circuitry. We will also test potential therapeutic treatments for
social jet lag in adolescents that might mitigate risk for SUD. Here we will use a noninvasive method of assessing
the human molecular clock using skin cells collected from hair follicles, which has been fully optimized for the
measure of molecular rhythms. However, no study to date has cultured cells from adolescents for molecular
rhythm measurement, associated molecular rhythms with other sleep, reward and circadian measures, or
investigated the effects of potentially therapeutic compounds on these rhythms. In Project 3 we will be utilizing
hair follicle samples collected in P1/2 from human subjects and combine this data with the thorough rhythm,
sleep, cognition, and reward data collected in those projects. We will also determine how molecular measures
in rodents correlate with behavioral and electrophysiological data collected in P4/5. Moreover, we are testing
potential pharmacological interventions on molecular rhythms which will inform future clinical trials. We are also
using rodents to provide detailed gene and protein expression in brain regions of interest in response to specific
manipulations of sleep and circadian rhythms. The questions we want to answer are: (1) How are sleep and
circadian rhythm phenotypes and addiction vulnerability related to molecular rhythms? This will be tested in both
humans and rats through cell culture studies. (2) What are the molecular mechanisms by which circadian rhythm
and sleep disruptions in combination or independently lead to increased vulnerability for substance abuse in
adolescents? This will be tested in rodents generated in Core B that have experienced specific sleep and
circadian manipulations followed by RNA sequencing and proteomics in PFC and NAc. (3) Are there
pharmacological interventions that will shift and/or amplify molecular rhythms in human subjects that could be
useful for adolescents with delayed chronotypes and circadian misalignment? This will be directly tested in cell
culture. Taken together, these studies could point towards novel treatments for adolescents that are at risk for
substance use disorders.

## Key facts

- **NIH application ID:** 10217072
- **Project number:** 5P50DA046346-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Colleen A McClung
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $299,592
- **Award type:** 5
- **Project period:** 2020-07-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217072

## Citation

> US National Institutes of Health, RePORTER application 10217072, Molecular rhythms and substance abuse vulnerability in adolescents (5P50DA046346-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10217072. Licensed CC0.

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