# Methamphetamine Effects on Prefrontal Cortical  PV+ Interneurons and Resulting Cognitive Deficits

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $358,625

## Abstract

Project Summary
 Neuropsychiatric disorders are a very serious medical and societal problem with many different origins,
however, a common and prevalent deficit found in these disorders is hypofrontality. Emerging theories posit
that hypofrontality [alterations in the ratio of excitatory (E) and inhibitory (I) synaptic transmission] underlie
schizophrenia, anxiety, addiction, autism spectrum disorders and depression.
 Methamphetamine (METH) addicts frequently develop hypofrontality and deficits in working memory
(WM), attention, and impulsivity. Similarly, in rodents, repeated psychostimulant administration or self-
administration elicits hypofrontality, WM deficits, psychosis-like behaviors, decreased interest in external
stimuli and surroundings, and decreased social functioning, suggesting that psychostimulant administration
in rodents represents a strong, face-valid model for studying the basic brain mechanisms that underlie
hypofrontality and cognitive disabilities in METH addiction.
 The overall objective of the proposed studies is to identify the effects of METH-SA on the activity of cortical
parvalbumin positive fast spiking interneurons (PV+FSIs) and the resulting changes in E-I ratio.
The central hypothesis- informed by strong preliminary data and literature- is that METH treatment elicits
cognitive deficits due to an increase in GABAergic synaptic transmission in the PFC via D1R activation of
PV+FSIs. The proposal’s rationale is that the experiments will yield fundamental knowledge pertaining to the
understanding of the cellular and synaptic mechanisms underlying hypofrontality induced by METH and will
provide new insights into the basic mechanisms governing E-I balance in the prefrontal cortex. We will test the
central hypothesis by pursuing the following specific aims: Aim 1 will determine the role of PV+FSIs in METH-
induced cognitive deficits. Aim 2 will determine whether D1R signaling in PFC PV+FSIs is required for METH-
induced enhancements of GABAergic transmission. Aim 3 will determine whether D1R signaling in PFC
PV+FSIs is required for METH SA-induced cognitive deficits and METH reinstatement.
 The proposed research is significant because it will fill a fundamental gap in knowledge pertaining to the
mechanisms underlying hypofrontality in METH-addiction and the effects of the psychostimulant in the activity
of cortical PV+FSIs. Furthermore, the knowledge obtained from the proposed experiments will help to develop
effective treatments to ameliorate drug-related cognitive deficits and can provide new insights into the basic
mechanisms underlying hypofrontality in other neuropsychiatric conditions.

## Key facts

- **NIH application ID:** 10886705
- **Project number:** 5R01DA054589-04
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** ANTONIETA LAVIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $358,625
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10886705

## Citation

> US National Institutes of Health, RePORTER application 10886705, Methamphetamine Effects on Prefrontal Cortical  PV+ Interneurons and Resulting Cognitive Deficits (5R01DA054589-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10886705. Licensed CC0.

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