# The Orexin System as a Target for PTSD and Comorbid Psychosis

> **NIH VA I01** · SOUTH TEXAS VETERANS HEALTH CARE SYSTEM · 2021 · —

## Abstract

Project Summary/Abstract:
Psychotic symptoms are highly prevalent in PTSD patients and are typically treated with dopamine D2 receptor
antagonists; however, these drugs are associated with significant adverse effects. We have novel preliminary
data demonstrating that the paraventricular nucleus of the thalamus (PVT) regulates dopamine neuron activity.
We posit that the PVT therefore represents a potential therapeutic target for the treatment of PTSD as well as
comorbid psychosis. The PVT receives a particularly dense innervation from orexin containing neurons in the
hypothalamus. Thus, the orexin system is well positioned to regulate PVT activity and may be a novel target for
pharmacological intervention. One such drug, Suvorexant, an orexin receptor antagonist, is currently FDA-
approved for the treatment of insomnia. We will test the hypothesis that Suvorexant can reverse deficits in
rodents displaying circuit level alterations and corresponding behavioral deficits relevant to comorbid psychosis
in PTSD. Specifically, we will examine whether orexin receptor antagonists can reverse stress-induced
behavioral (Aim 1) or neurophysiological/neurochemical (Aim 2) deficits associated with PTSD. We will then
determine the role of discrete PVT projections to the nucleus accumbens in comorbid psychosis (Aim 3). This
proposal with therefore identify a potential novel therapeutic target and inform the development of more effective
treatment approaches for PTSD and comorbid psychosis.

## Key facts

- **NIH application ID:** 10119151
- **Project number:** 5I01BX004693-02
- **Recipient organization:** SOUTH TEXAS VETERANS HEALTH CARE SYSTEM
- **Principal Investigator:** Daniel Lodge
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10119151

## Citation

> US National Institutes of Health, RePORTER application 10119151, The Orexin System as a Target for PTSD and Comorbid Psychosis (5I01BX004693-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10119151. Licensed CC0.

---

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