# Neurodevelopmental Effects of THC on The VTA Dopamine System and Behavior

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $335,072

## Abstract

PROJECT SUMMARY
Marijuana is the most common illicit drug used by pregnant women. Clinical studies on the long-term effects of
marijuana smoking during pregnancy show its detrimental impact on the cognitive development of the offspring
from early childhood until later in life. In fact, children and adolescents exposed to the psychoactive ingredient
of marijuana, Δ9-tetrahydrocannabinol (THC), before birth display reduced attention, learning and problem
solving, hyperactivity, increased impulsivity and engagement in risk-taking behaviors. Hence, early exposure to
THC might induce enduring adaptations encompassing the brain reward dopamine (DA) system resulting in
maladaptive behavior, ranging from affective dysregulation to addiction vulnerability. However, preclinical
studies on the impact of marijuana use on the development of brain reward pathways are surprisingly lacking.
Hence, there is an urgent need to identify molecular substrates and effective strategies for prevention and
treatment of these detrimental effects that might confer individual vulnerability. Here, we propose three
experiments to test our overarching hypothesis that prenatal THC exposure induces a strengthening at afferent
excitatory synapses on ventral tegmental area (VTA) DA neurons, which together with abnormal
endocannabinoid (ECB) system function, induces a persistent excitatory drive to DA neurons underlying an at-
risk phenotype for alcohol seeking. First, we will determine if prenatal THC exposure leads to strengthening of
excitatory transmission onto VTA DA cells and we will examine the pathological reorganization of the ECB
system's molecular machinery with nanoscale precision (Aim 1). Next, we will test whether offspring of THC-
exposed dams display increased sensitivity to natural rewards and vulnerability to alcohol dependence in
adulthood by means of biochemical and behavioral readouts (Aim 2). Finally, we will explore a postnatal
pharmacological intervention to reverse the deleterious effects of prenatal exposure to THC (Aim 3). To our
knowledge, these research issues have never been specifically addressed in this multi-disciplinary manner.
We will test our hypothesis by exposing rat dams to THC during pregnancy and by combining ex vivo
electrophysiological recordings, pharmacological manipulations, neurochemical detection schemes along with
sophisticated Stochastic Optical Reconstruction Microscopy (STORM) super-resolution imaging and behavioral
paradigms in the offspring of THC-treated dams. We will take advantage of the coordinated expertise of
multiple laboratories and we will ensure that studies will be carried out in parallel rather than serially in a single
laboratory. This will lead to an advance of scientific knowledge through international collaborative research that
will simultaneously impact public awareness and policy makers of three different countries.

## Key facts

- **NIH application ID:** 10162575
- **Project number:** 5R01DA044925-04
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Joseph F Cheer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $335,072
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10162575

## Citation

> US National Institutes of Health, RePORTER application 10162575, Neurodevelopmental Effects of THC on The VTA Dopamine System and Behavior (5R01DA044925-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10162575. Licensed CC0.

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