# Persistent Impacts of Adolescent THC on Microglial Function and Opioid Addiction Risk

> **NIH NIH F99** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $46,563

## Abstract

Project Summary
Adolescent cannabis use has been linked to negative long-term outcomes in humans, including increased rates
of experimentation with “harder” drugs like opioids later in life. Yet these associations cannot be tested causally
in humans, so animal studies showing that adolescent THC exposure (adoTHC) indeed causes developmental
disruption of reward and cognition circuits are notable and potentially alarming. Here we employ a well-
characterized, translationally-oriented adoTHC exposure model in rats to examine how opioid-addiction relevant
behaviors are altered, and to uncover novel brain mechanisms by which these behavioral changes may manifest.
Notably, microglia, the resident immune cells of the brain, are increasingly being recognized for their key roles
in neurodevelopment, including in adolescence. In pursuit of a mechanistic understanding that can inform novel
interventions or strategies for opioid addiction, my project examines the effects of adoTHC exposure on
microglia, and how these changes may impact opioid drug seeking behavior.
I employ translationally relevant behavioral models of opioid addiction in rats to fully characterize the adoTHC-
induced pro-opioid phenotype, and employ both hypothesis-generating RNA sequencing approach, as well as
an experimental microglial “resetting” approach to test the causal relevance of microglia in the observed pro-
opioid behavioral phenomena seen in males and females.
During the F99 phase of this award, I will replicate and extend my findings, and obtain training and new data
employing RNA sequencing of FACS-isolated microglia in prefrontal cortex. The proposed training will
facilitate my transition to a competitive postdoctoral position focused on in vivo imaging and monitoring of
microglia, building upon my current expertise in addiction behavioral models. My sponsors will be instrumental
in helping me build skills in experimental design, guided analyses support, scientific communication, and
grantsmanship. They will also guide me in finding a postdoctoral training environment focused in
neuroimmunology aligning with my long-term research and career goals. Altogether, the F99/K00 award serves
as an invaluable asset in propelling me on a trajectory towards becoming a tenure-track addiction behavioral
neuroscientist.

## Key facts

- **NIH application ID:** 11075526
- **Project number:** 1F99NS141399-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Maricela Xochil Martinez
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $46,563
- **Award type:** 1
- **Project period:** 2024-09-13 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11075526

## Citation

> US National Institutes of Health, RePORTER application 11075526, Persistent Impacts of Adolescent THC on Microglial Function and Opioid Addiction Risk (1F99NS141399-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11075526. Licensed CC0.

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