# Aberrant dopamine system function in a rodent model of perimenopause: relevance to psychosis

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2024 · $317,184

## Abstract

Project Summary/Abstract:
The transition to menopause (or perimenopause) is a period of unique vulnerability for a woman, in which there
is an increased risk of developing a psychotic disorder or the exacerbation of a pre-existing condition, such as
first onset schizophrenia/psychosis or bipolar disorder. Antipsychotics used to treat symptoms of psychosis, are
not always effective and are often discontinued due to adverse side effects. Further, when given to
perimenopausal women, antipsychotics can worsen common symptoms of this period (i.e., weight gain and
hyperprolactinemia). This is important to note because psychotic symptoms are debilitating and can severely
affect a woman’s quality of life. In the present proposal we will provide a mechanistic understanding into how
aberrant regulation of the mesolimbic dopamine system, by the ventral hippocampus, contributes to symptoms
of psychosis during perimenopause. We will address this using in vivo electrophysiology, chemogenetics, and
behavior with three specific aims: 1) Examine vHipp regulation of VTA dopamine neurons and dopamine-
dependent behaviors associated with psychosis in the VCD rodent model of perimenopause. 2) Evaluate the
impact of age on the psychosis-like effects of VCD. 3) Determine the utility of α5-GABAAR PAMs as a therapeutic
intervention for restoring dopamine system function and dopamine-dependent behaviors associated with
perimenopause in the VCD model. Our overarching hypothesis is that aberrant vHipp regulation of the
mesolimbic dopamine system during perimenopause underlies behavioral changes associated with psychosis.
Furthermore, we posit that α5-GABAAR modulators may have therapeutic utility during the menopausal
transition.

## Key facts

- **NIH application ID:** 10936510
- **Project number:** 5R01AG076030-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Daniel Lodge
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $317,184
- **Award type:** 5
- **Project period:** 2023-09-30 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10936510

## Citation

> US National Institutes of Health, RePORTER application 10936510, Aberrant dopamine system function in a rodent model of perimenopause: relevance to psychosis (5R01AG076030-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10936510. Licensed CC0.

---

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