# Early postnatal disruptions to glutamate and GABA systems and their contribution to reward deficits

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $403,100

## Abstract

7. Project Summary/Abstract
Deficits in reward function, including impaired reward valuation, effort valuation and reward responsiveness,
are core features of psychiatric disorders, such as schizophrenia and major depressive disorder. These reward
deficits contribute significantly to the functional disability evident in these disorders. These reward processes
correspond to approach/motivation constructs within the Positive Valence Domain of the NIMH Research
Domain Criteria (RDoC) Program. The neurobiology underlying reward deficits is not completely understood
and, as a result, there are currently no therapeutics that effectively alleviate reward deficits in psychiatric
disorders. Schizophrenia and depression are both associated with abnormalities in glutamate and GABA
neurotransmission. The GABAergic system is essential in regulating correct glutamatergic transmission that
maintains optimal cortical balance. Importantly, postnatal glutamate transmission is critical for the normal
development of the GABAergic system. The overarching goal of this R01 application is to investigate how
disrupting early postnatal glutamate transmission leads to reward deficits in adulthood. To address this
experimental question, we will employ translational behavioral procedures in rats, optogenetics and
immunohistochemical techniques to identify the role of altered glutamate and/or GABA transmission in brain
regions associated with reward processing. Specific Aim 1 will determine whether administering the N-methyl-
D-aspartate (NMDA) glutamate receptor antagonist phencyclidine (PCP) during the early postnatal period to
male and female rats impairs reward valuation, effort valuation and/or reward responsiveness. Specific Aim 2
will use optogenetics to either increase or decrease glutamate activity in the orbitofrontal cortex (OFC) or
anterior cingulate cortex (ACC) to determine whether such changes in glutamate activity impact reward
valuation, effort valuation or reward responsiveness. Specifically, we will determine whether increased or
decreased glutamate transmission impairs or improves reward processing in saline- or PCP-treated rats.
These findings will provide evidence as to how changes in glutamate transmission lead to the regulation of
multiple aspects of reward processing mediated by distinct brain regions. Specific Aim 3 will determine whether
the reward deficits resulting from neonatal PCP treatment are associated with alterations in parvalbumin (PV)-,
somatostatin (SST)- and/or vasoactive intestinal polypeptide (VIP)-positive GABA interneurons, and glutamic
acid decarboxylase isoform 67 (GAD67) content, in brain regions critical for reward function (i.e., OFC,
prelimbic cortex, anterior cingulate cortex, dorsal striatum and/or ventral striatum). This multidisciplinary project
will promote our understanding of how alterations in neurobiology resulting from neonatally disrupted glutamate
transmission contribute to deficits in reward function in adulthood....

## Key facts

- **NIH application ID:** 9925254
- **Project number:** 5R01MH108653-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Samuel Alan Barnes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $403,100
- **Award type:** 5
- **Project period:** 2016-07-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925254

## Citation

> US National Institutes of Health, RePORTER application 9925254, Early postnatal disruptions to glutamate and GABA systems and their contribution to reward deficits (5R01MH108653-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9925254. Licensed CC0.

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