# Determining the role of adolescent sleep and circadian factors on risk for substance use in a rat model

> **NIH NIH P50** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $295,669

## Abstract

PROJECT SUMMARY
Adolescence is a period of enhanced vulnerability to develop substance use disorders in part do to the ongoing
development of neural circuits associated with reward and executive function (i.e., impulsivity, attention, reward
sensitivity). In addition, adolescents experience a developmentally regulated shift in circadian rhythms to a more
evening chronotype and have less perceived sleep drive. Thus, adolescents are biologically driven to stay up
later at night and wake later in the morning. However, this natural shift in circadian rhythms is in conflict with
societal norms, particularly early school start times, which can lead to a chronic state of circadian misalignment
and insufficient sleep. The degree to which chronic circadian and sleep disturbances in adolescence impacts
brain development and risk for drug abuse is not well understood. Moreover, there is a wide variation in the
degree of circadian shift amongst adolescents, leading to the possibility that certain individuals are more at risk
than others for circadian and sleep-associated dysfunction. Therefore, an increased understanding of the
behavioral and neural consequences of sleep and circadian disturbances, and their interaction with individual
differences in sleep and circadian preferences, is needed to inform new interventions and preventative
strategies. Project 4 of the Center for Adolescent Reward, Rhythms, and Sleep (CARRS) aims to determine
the effects individual differences in chronotype (Aim 1), circadian misalignment in the absence of sleep loss (Aim
2), and acute and chronic sleep disruption (Aim 3) on behavioral indices of addiction risk and corticolimbic neural
activity in adolescent rats. Identification of individual differences in sleep and circadian preferences will be
facilitated by using the heterogeneous stock (HS) outbred rats that produce more variability than standard
outbred strains, and allow for precise genetic identification of trait differences. Rats will be phenotyped for
circadian and sleep preferences in early adolescence by our Phenotyping and Bio-banking Core B. We will
then examine how these phenotypes related to impulsivity and execute function on the 5-choice serial reaction
time task (5-CSRTT) and if rats with extreme chronotypes (early vs. late) exhibit differences in nicotine or THC
self-administration. Aims 2 and 3 will focus on how manipulations of circadian rhythms and sleep alter behavior
on the 5-CSRTT and drug self-administration. In addition, we will test how corticolimbic activity is altered by
circadian and sleep manipulations during behavior using in vivo fiber photometry. Results of these studies will
be integrated with human neuroimaging data obtained in Projects 1 and 2, and with the molecular and ex vivo
electrophysiological results obtained in Projects 3 and 5.

## Key facts

- **NIH application ID:** 10217073
- **Project number:** 5P50DA046346-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Mary M Torregrossa
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $295,669
- **Award type:** 5
- **Project period:** 2020-07-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217073

## Citation

> US National Institutes of Health, RePORTER application 10217073, Determining the role of adolescent sleep and circadian factors on risk for substance use in a rat model (5P50DA046346-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10217073. Licensed CC0.

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