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Journal article
Astrocytic HIV-1 Nef Expression Decreases Glutamate Transporter Expression in the Nucleus Accumbens and Increases Cocaine-Seeking Behavior in Rats
pharmaceuticals, v 18(1), 40
01 Jan 2025
PMID: 39861103
Featured in Collection : Research Supported by Drexel Libraries' OA Programs
Abstract
Background/Objectives: Cocaine use disorder is an intersecting issue in populations with HIV-1, further exacerbating the clinical course of the disease and contributing to neurotoxicity and neuroinflammation. Cocaine and HIV neurotoxins play roles in neuronal damage during neuroHIV progression by disrupting glutamate homeostasis in the brain. Even with combined antiretroviral therapy (cART), HIV-1 Nef, an early viral protein expressed in approximately 1% of infected astrocytes, remains a key neurotoxin. This study investigates the relationship among Nef, glutamate homeostasis, and cocaine in the nucleus accumbens (NAc), a critical brain region associated with drug motivation and reward. Methods: Male and female Sprague Dawley rats were used to compare the effects of astrocytic Nef and cocaine by molecular analysis of glutamate transporters, GLT-1 and the cysteine glutamate exchanger (xCT), in the NAc. Behavioral assessments for cocaine self-administration were used to evaluate cocaine-seeking behavior. Results: The findings indicate that both cocaine and Nef independently decrease the expression of the glutamate transporter GLT-1 in the NAc. Additionally, rats with astrocytic Nef expression exhibited increased cocaine-seeking behavior but demonstrated sex-dependent molecular differences after the behavioral paradigm. Conclusions: The results suggest that the expression of Nef intensifies cocaine-induced alterations in glutamate homeostasis in the NAc, potentially underlying increased cocaine-seeking behavior. Understanding these interactions better may inform therapeutic strategies for managing cocaine use disorder in HIV-infected individuals.
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Details
- Title
- Astrocytic HIV-1 Nef Expression Decreases Glutamate Transporter Expression in the Nucleus Accumbens and Increases Cocaine-Seeking Behavior in Rats
- Creators
- Jessalyn Pla Tenorio (Corresponding Author) - Drexel University, Pharmacology and PhysiologyBethzaly Velazquez-Perez - Ponce Health Sciences UniversityYainira Mendez-Borrero - Ponce Health Sciences UniversityMyrella L. Cruz - Ponce Health Sciences UniversityMarian T. Sepulveda-Orengo - Ponce Health Sciences UniversityRichard J Noel - Ponce Health Sciences University
- Publication Details
- pharmaceuticals, v 18(1), 40
- Publisher
- MDPI
- Number of pages
- 21
- Grant note
- NIH: 1F31DA05481-01A1, RCMI MD007579, R25GM082406, P20 GM103475-19, NIMHD 3U54MD007579-37S1, CRG-2020-00114
This study was supported by NIH Grants: 1F31DA05481-01A1, RCMI MD007579-Molecular Core and BRAIN Core, Fundacion Intellectus, RISE Program R25GM082406, PR-INBRE Developmental Research Project Program P20 GM103475-19, RCMI-Supplement Project NIMHD 3U54MD007579-37S1, and Catalyzer Research Grants Program (CRG-2020-00114).
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:001403930600001
- Scopus ID
- 2-s2.0-85216093893
- Other Identifier
- 991022008293304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Chemistry, Medicinal
- Pharmacology & Pharmacy