# Targeting Phospholipase C and Dendritic Spines to Reduce Cocaine and Heroin Motivation

> **NIH NIH K01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2021 · $188,525

## Abstract

This grant will establish new independent investigator studies on maladaptive neuroplasticity induced by
chronic use of the addictive drugs cocaine and heroin. This project will be led by Ethan Anderson, Ph.D.; an
energetic, passionate, and productive researcher on a trajectory to develop an independent research position
studying drug addiction. This project will take place at the Medical University of South Carolina (MUSC), an
institute with a stellar reputation for producing high quality researchers that specialize in drug addiction. Dr.
Anderson will be mentored Dr. Chris Cowan and Dr. Peter Kalivas at MUSC. These mentors have successfully
trained scientists who have gone on to faculty positions at major universities and are experts in behavioral
models of drug addiction, biochemical, molecular, and structural changes in the brain due to chronic drug use,
and the generation of novel tools to investigate these mechanisms of addiction. This overall project will employ
2 novel and innovative approaches to investigate and reverse the negative effects of both cocaine and heroin
on morphological and behavioral changes underlying addiction. The short-term goals of this project involve 2
aims: 1) Determine the intracellular mechanism of a novel, endogenous anti-addictive signaling pathway
through and phospholipase Cᵧ1 (PLC) as a potential new target for reducing opioid use in humans. 2) Reverse
cocaine-induced maladaptive changes in synapses in the nucleus accumbens by selectively targeting and
optogenetically removing dendritic spines recently activated by cocaine. This will determine whether a direct
causal relationship exists between reversal of these morphological brain changes and alterations in addictive
behavior. The scientific training program for Dr. Anderson will focus on learning 3 new skills: 1) optogenetics
with novel in vivo spine reduction technology, 2) heroin self-administration behavior, and 3) cloning and
molecular biological techniques necessary for constructing novel viral vectors. In addition, Dr. Anderson will
receive excellent career development training via an outstanding career advisory committee (Drs. Eric Nestler,
David Self, Arthur Riegel, and Jacqueline McGinty) and specific individual career training from Drs. Cowan and
Kalivas. The individual scientific training will include individual meetings with his mentors to discuss and
prepare future R01 applications, presentations at seminars and 1-2 conferences per year, the publication of 1
paper every 1-2 years, and didactic course work in drug addiction and cutting-edge molecular biology. This
grant will pave the way for Dr. Anderson to achieve his potential to become a productive, R01 fundable,
independent scientist in the field of addiction research by allowing him to learn new scientific skills, produce
high-impact data, receive excellent and broad-based training with expertise from his advisors and mentors, and
study in the exceptional training grounds of MUSC.

## Key facts

- **NIH application ID:** 10129326
- **Project number:** 5K01DA046513-03
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Ethan Michael Anderson
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $188,525
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129326

## Citation

> US National Institutes of Health, RePORTER application 10129326, Targeting Phospholipase C and Dendritic Spines to Reduce Cocaine and Heroin Motivation (5K01DA046513-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10129326. Licensed CC0.

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