# Genetic Targeting Core

> **NIH NIH P30** · UNIVERSITY OF ARIZONA · 2024 · $373,005

## Abstract

Project Summary – Genetic Targeting Core
Substance use disorders (SUD) are characterized by dysregulation of brain circuitry that involves diminished
activity of the brain reward circuits, increased responsiveness of the stress circuits and impaired functioning of
the executive cortical circuits. Neural changes are observed in the basal ganglia, extended amygdala and
prefrontal cortical regions and encompass a wide range of endogenous neurotransmitters including dopamine,
opioid peptides, endocannabinoids, corticotropin releasing factor (CRF), dynorphin, glutamate and others. It
implies that these maladaptations may be causally responsible for behavioral changes often observed in chronic
drug users, for example habit formation and compulsive drug taking, that further worsen the neuronal and
behavioral signs of SUD. Restoration of normal functioning of the brain circuits is therefore a desirable goal of
SUD therapies. However, the exact influence of chronic drug use on the addiction brain circuits and how
manipulation of these circuits could prevent or treat substance use disorders remains to be elucidated.
As part of the Center of Excellence in Addiction Studies, the Genetic Targeting Core (GT Core) will assist users
in obtaining preliminary data on neural mechanisms of addiction that will form basis for future NIDA grant
applications. The GT Core will provide services to target and manipulate the addiction circuits in a cell specific
and circuits specific manner using state-of-the-art genetic techniques, including optogenetics, chemogenetics
and CRISPR/Cas9 gene editing. Optogenetic strategies use microbial-based light activated ion channels
(opsins) that allow fast neuronal activation (channelrhodopsins) or inhibition (halorhodopsins,
archaerhodopsins), while chemogenetic approaches use engineered ion channels (PSAMs) or G protein-
coupled receptors (DREADDs) that can be activated pharmacologicaly. CRISPR/Cas9 gene editing allows direct
in vivo manipulation of the genome in rodents. The introduction of functional transgenes, such as opsins and
DREADDs or editing of native genes requires in vivo delivery and expression of genetic material in desired cells.
This is accomplished with viral or nonviral vector systems. Cell and circuit specificity can be further enhanced by
the use of a specific Cre-driver mouse line.
The GT Core will provide three main services to its users that correspond with the three Specific Aims: 1) assist
with the selection of gene targeting methods, including the choice of the transgenic mouse line, and the type of
viral vector; 2) optimize and implement gene delivery using high precision stereotaxic instruments; and 3) verify
the efficacy of gene targeting using fluorescent microscopy or protein and gene quantification techniques. The
GT Core will coordinate work with the Administrative, Behavioral and Neuroanalytical Cores to develop effective
experimental strategies that involve several Cores. The close collaboration bet...

## Key facts

- **NIH application ID:** 10899449
- **Project number:** 5P30DA051355-04
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Edita Navratilova
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $373,005
- **Award type:** 5
- **Project period:** 2021-08-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899449

## Citation

> US National Institutes of Health, RePORTER application 10899449, Genetic Targeting Core (5P30DA051355-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10899449. Licensed CC0.

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