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Journal article
Chemogenetic activation of medial prefrontal cortex projections to the nucleus accumbens shell suppresses cocaine-primed reinstatement in EcoHIV infected mice
Psychopharmacology
16 Jul 2025
PMID: 40668359
Featured in Collection : Research Supported by Drexel Libraries' OA Programs
Abstract
HIV is highly comorbid with cocaine use disorder (CUD). Relapse is a major challenge in the treatment of CUD, and people living with HIV (PLWH) exhibit shorter time to relapse. One driver of relapse may be re-exposure to cocaine, which can be modeled in rodents using cocaine-primed reinstatement. This process involves neuroadaptations within the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) shell, regions that mediate cocaine reward learning and relapse-related behavior. HIV infection interacts with cocaine to alter corticostriatal circuits, which may further dysregulate cocaine seeking. To investigate the impact of HIV infection on cocaine reward learning and reinstatement and the role of mPFC-NAc circuits, we utilized the EcoHIV mouse model, a chimeric form of HIV-1 which can infect wild-type mice. Our findings demonstrate that EcoHIV infection enhances cocaine-primed reinstatement. We also observed increased cocaine-induced expression of the cellular activation marker cFos in the NAshell in EcoHIV-infected mice. Given the role of the mPFC-NAshell circuit in cocaine-seeking behaviors, we further demonstrated that chemogenetic activation of this circuit could reverse the behavioral deficits induced by EcoHIV. We propose that HIV infection contributes to neuroadaptations in the mPFC-NAshell circuit, and enhancing its activity may inhibit relapse-related behavior. These findings indicate that key neuronal circuits underlying cocaine reinstatement are similarly implicated in HIV infection and suggest potential strategies for managing relapse in PLWH.
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Details
- Title
- Chemogenetic activation of medial prefrontal cortex projections to the nucleus accumbens shell suppresses cocaine-primed reinstatement in EcoHIV infected mice
- Creators
- Qiaowei Xie - Drexel UniversityMark Douglas Namba - Drexel University, Pharmacology and PhysiologyRohan Dasari - Drexel UniversityLauren Ashley Buck - Drexel University, Pharmacology and PhysiologyChristine Marie SideSamuel L Goldberg - Drexel University, Pharmacology and PhysiologyKyewon Park - University of PennsylvaniaJoshua G Jackson - Drexel University, Pharmacology and PhysiologyLaura L Giacometti - Drexel University, Pharmacology and PhysiologyJacqueline M Barker (Corresponding Author) - Drexel University, Pharmacology and Physiology
- Publication Details
- Psychopharmacology
- Publisher
- Springer Nature
- Number of pages
- 14
- Grant note
- Foundation for the National Institutes of Health: DP2DA051907, R21DA056309, R01AG081929, F32DA060768 NIH: P30MH092177-9 Comprehensive Neuro-AIDS Center
We would like to thank Dr. David Volsky for providing the EcoHIV-NDK plasmid. The authors would also like to thank Bryan Roth for providing the pAAV-hSyn-hM3D(Gq)-mCherry and Karl Deisseroth for the control virus pAAV-hSyn-mCherry. This research was supported by NIH award DP2DA051907 (JMB), R21DA056309 (JGJ), R01AG081929 (JGJ), F32DA060768 (MDN), and pilot awards from The Comprehensive Neuro-AIDS Center Grant P30MH092177-9 (JMB and MDN).
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; Pharmacology and Physiology
- Web of Science ID
- WOS:001530170200001
- Scopus ID
- 2-s2.0-105010843299
- Other Identifier
- 991022064142004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences
- Pharmacology & Pharmacy
- Psychiatry