# Investigating the lasting effects of adolescent cannabinoid exposure on mesocortical development

> **NIH NIH K99** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $141,438

## Abstract

Project Abstract
Adolescence is a period of significant neuronal development as well as the time when many individuals initiate
cannabis use. Delta-9-tetrahydrocannabinol (THC) is one of the main psychoactive components found in
cannabis, and THC exposure during adolescence has previously been associated with lasting cognitive deficits.
In this proposal, I will investigate how self-administration of THC during adolescence influences GABAergic
activity in mesocortical brain regions, and how these changes contribute to executive function in adulthood.
Using a rodent model of intravenous THC self-administration, my preliminary data indicate that there is a dose-
and sex-dependent effect of THC self-administration on performance of a complex working memory task. THC-
exposed animals also exhibit reduced expression of cannabinoid and GABAergic receptors, primarily in the
prelimbic cortex and ventral tegmental area. A major question remains concerning the cell type-specificity of
these changes, and how they may interact drug exposure and sex to influence behavioral outcomes in adulthood.
In the proposed studies, I will investigate the molecular, neurotransmitter, and circuit-level changes that are
induced by THC self-administration. During the mentored K99 phase of this project, I will develop new skills in
advanced multi-label fluorescent immunohistochemistry and imaging of GABAergic synapses in the prelimbic
cortex of male and female rats. I will assess the presynaptic and postsynaptic alterations that are associated
with THC self-administration and cognitive training. I will then acquire training using fiber photometry and
optogenetics to understand how GABAergic neurotransmission contributes to the performance of prefrontal
cortex-dependent cognitive tasks, and how THC self-administration influences this pattern of neuronal activation
and neurotransmitter activity. During the independent R00 phase, I will investigate circuit-level contributions of
the ventral tegmental area and prefrontal cortex to synchronous activity during these behaviors and assess how
THC self-administration may modify this activity using electrophysiology. I will also determine how THC self-
administration contributes to the development of dopaminergic synaptic inputs in the prelimbic cortex. I have
gathered a diverse and experienced mentoring team of expert faculty to provide technical and professional
guidance throughout my training and transition to independence. In total, the studies for this award will shed light
on the molecular and circuit level changes to mesocortical brain regions associated with exposure to self-
administered doses of THC during adolescence. This project will also provide training in the skills necessary to
establish an independent career that utilizes techniques that bridge cellular and circuit-level investigation of the
effects of drug use and abuse.

## Key facts

- **NIH application ID:** 10523713
- **Project number:** 1K99DA054205-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** SIERRA STRINGFIELD
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $141,438
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10523713

## Citation

> US National Institutes of Health, RePORTER application 10523713, Investigating the lasting effects of adolescent cannabinoid exposure on mesocortical development (1K99DA054205-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10523713. Licensed CC0.

---

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