# Impact of alterations in mesolimbic innervation of the prefrontal cortex following adolescent alcohol exposure.

> **NIH NIH F32** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $43,035

## Abstract

PROJECT SUMMARY
Individuals that binge drink alcohol during adolescence are more likely to develop chronic, relapsing alcohol
disorders at some point in their life. Studies in animals have also shown that repeated episodes of adolescent
alcohol exposure lead to dysregulation of the medial prefrontal cortex (PFC) and deficits in inhibitory control and
behavioral flexibility in adulthood. The goal of this proposal is to utilize a rodent model of adolescent intermittent
ethanol (AIE) exposure to investigate mechanisms involved in alcohol-induced deficits in prefrontal function and
behavioral control in adulthood. Recent research suggests that a subset of ventral tegmental area (VTA)
dopaminergic projection neurons that initially innervate the nucleus accumbens (NAc) subsequently grow to the
PFC, a process that is important for executive function in adulthood. While our lab has shown that AIE
significantly impacts dopaminergic neurotransmission and regulation in the prelimbic (PrL) subregion of the PFC,
it is unknown if the newly identified VTA-NAc-PrL pathway is altered by AIE exposure. Synaptic pruning in the
medial PFC and NAc during adolescence is critical for inhibitory control and behavioral flexibility. Interestingly,
accumulating data indicates that this process is facilitated through glial-mediated phagocytosis. Although it is
known that alcohol can alter neuroimmune signaling, whether AIE exposure affects glial/neural interactions and
glial morphology is not well understood. The overarching hypothesis of the current proposal is that AIE exposure
reduces VTA innervation and neural/glial interactions in the PrL cortex, contributing to alterations in adult
behavior. Specific Aim 1 will test the hypothesis that AIE exposure reduces the developmental innervation and
synaptic refinement of VTA originating DA projections in the PrL cortex. This aim will use axon-initiated viral
transduction, immunofluorescence, and advanced super-resolution confocal microscopy and 3D analysis to
examine innervation of the PrL by VTA-DA neurons whose axons initially terminated in the NAc and then grew
to the PrL during adolescence. In order to gain a broader perspective of alterations within the PrL-NAc circuit
following AIE, studies will also examine glial interactions with PrL neurons that project back to the NAc. Specific
Aim 2 will test the hypothesis that AIE and inhibition of the VTA-NAc-PrL projection will similarly alter active and
passive avoidance in adulthood. This aim will gain insight into the impact of AIE and the VTA-NAc-PrL projection
on behavioral flexibility. The novel platform-mediated avoidance task allows for the simultaneous investigation
of both passive and active avoidance, an area in the developmental literature on AIE that has been relatively
overlooked. Studies will also determine whether DREADD-mediated inhibition of the VTA-NAc-PrL pathway
alters adult avoidance behavior in a similar manner to AIE. The novel conceptual nature of this pr...

## Key facts

- **NIH application ID:** 10026016
- **Project number:** 5F32AA027951-02
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Justine Landin
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $43,035
- **Award type:** 5
- **Project period:** 2019-09-29 → 2021-04-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10026016

## Citation

> US National Institutes of Health, RePORTER application 10026016, Impact of alterations in mesolimbic innervation of the prefrontal cortex following adolescent alcohol exposure. (5F32AA027951-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10026016. Licensed CC0.

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