# Neural Signatures and Cognitive Performance During Rat Morphine Withdrawal, and Subsequent Impact of Psilocybin

> **NIH NIH F31** · UNIVERSITY OF WASHINGTON · 2024 · $47,405

## Abstract

PROJECT ABSTRACT
Opioid addiction is pervasive and widespread, affecting roughly three million U.S. adults. Currently available
opioid addiction treatments, such as opioid replacement therapy, fail to slow the growing opioid pandemic and
maintain the risk of addiction and overdose. Moreover, available opioid addiction treatments require long-term
commitment to treatment with little evidence of long-lasting abstinence. Lastly, opioid replacement therapy is
unable to alleviate addiction-induced cognitive impairments. A deeper understanding of the neural and
cognitive systems that underlie addiction is necessary for the development of better targeted treatments for
opioid addiction.
The rodent model of opioid addiction exhibits behavioral markers analogous to those induced in human opioid
addiction. Hence, this is a reliable and feasible model for studies of the neural correlates of addiction-related
maladaptive behaviors. An emerging body of research suggests that the evolutionarily conserved lateral
habenula in rodents is highly implicated in addiction. The lateral habenula is unique in that it directly regulates
dopaminergic and serotonergic structures, both of which exhibit dysfunction in addiction. However, with
traditional electrophysiological methods of recording lateral habenula neural activity, it has been difficult to
clearly assess responses of large populations of neurons. More recent advances in imaging technology have
allowed for week-long monitoring of individual neuron calcium dynamics, easing the feasibility of studying the
lateral habenula neural responses. Serotonin agonists, such as psilocybin, have shown promising results in
reducing the rates of relapse in alcohol and nicotine addiction and improving cognitive function in unhealthy
adults. Importantly, lateral habenula hyperactivity is known to drive aversion and is present in withdrawal.
Serotonergic agonists have also been shown to quiet lateral habenula activity, suggesting a potential
unexplored treatment avenue.
Hence, with the use of calcium imaging, I hypothesize that lateral habenula neuron dynamics will shift to a
hyperactive state following morphine withdrawal, and that these neural signatures will correlate with
decreased performance on cognitive tasks. Additionally, I hypothesize that psilocybin treatment will reinstate
baseline lateral habenula activity and improve cognitive performance. The proposed series of experiments will
fill the gap in understanding the neural circuitry that drives maladaptive decisions during opiate withdrawal, as
well as the behavioral and neural effect of a novel treatment for opiate addiction.

## Key facts

- **NIH application ID:** 10893977
- **Project number:** 5F31DA059250-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Victoria Ivanova Hones
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $47,405
- **Award type:** 5
- **Project period:** 2023-08-16 → 2026-08-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10893977

## Citation

> US National Institutes of Health, RePORTER application 10893977, Neural Signatures and Cognitive Performance During Rat Morphine Withdrawal, and Subsequent Impact of Psilocybin (5F31DA059250-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10893977. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*