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Journal article
Astrocytic regulation of cocaine locomotor sensitization in EcoHIV infected mice
Neuropharmacology, v 265, 110245
05 Dec 2024
PMID: 39631679
Featured in Collection : Research Supported by Drexel Libraries' OA Programs
Abstract
Cocaine use disorder (CUD) is highly comorbid with HIV infection and worsens HIV outcomes. Preclinical research on the outcomes of HIV infection may yield crucial information on neurobehavioral changes resulting from chronic drug exposure in people living with HIV (PLWH). Repeated exposure to cocaine alters behavioral responses to cocaine. This includes development of cocaine locomotor sensitization – or increased locomotor responses to the same doses of cocaine - which depends on nucleus accumbens (NAc) neural plasticity. NAc astrocytes are key regulators of neural activity and plasticity, and their function can be impaired by cocaine exposure and HIV infection, thus implicating them as potential regulators of HIV-induced changes in behavioral response to cocaine. To characterize the effects of HIV infection on cocaine locomotor sensitization, we employed the EcoHIV mouse model in male and female mice to assess changes in locomotor responses after repeated cocaine (10mg/kg) exposure and challenge. EcoHIV infection potentiated expression of cocaine sensitization. We also identified EcoHIV-induced increases in expression of the astrocytic nuclear marker Sox9 selectively in the NAc core. To investigate whether modulation of NAc astrocytes could reverse EcoHIV-induced deficits, we employed a chemogenetic approach. We found that chemogenetic activation of NAc astrocyte Gq signaling attenuated EcoHIV-enhanced cocaine sensitization. We propose that HIV infection contributes to cocaine behavioral sensitization and induces adaptations in NAc astrocytes, while promoting NAc astrocytic Gq-signaling can recover EcoHIV-induced behavioral changes. These findings identify potential cellular substrates of disordered cocaine-driven behavior in the context of HIV infection and point toward strategies to reduce cocaine-related behavior in PLWH.
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Details
- Title
- Astrocytic regulation of cocaine locomotor sensitization in EcoHIV infected mice
- Creators
- Jacqueline M Barker (Corresponding Author) - Drexel University, Pharmacology and PhysiologyQiaowei Xie - Drexel UniversityRohan Dasari - Drexel UniversityMark Douglas Namba - Drexel University, Pharmacology and PhysiologyLauren Ashley Buck - Drexel University, Pharmacology and PhysiologyChristine Marie Side - Drexel University, Pharmacology and PhysiologyKyewon Park - University of PennsylvaniaJoshua G Jackson - Drexel University, Pharmacology and Physiology
- Publication Details
- Neuropharmacology, v 265, 110245
- Publisher
- Elsevier
- Number of pages
- 12
- Grant note
- NIH: DP2DA051907, R21DA056309, R01AG081929 Comprehensive Neuro-AIDS Center: P30MH092177-9
This research was supported by NIH award DP2DA051907 (JMB) , R21DA056309 (JGJ) , R01AG081929 (JGJ) , 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:001374618600001
- Scopus ID
- 2-s2.0-85211066058
- Other Identifier
- 991021965771104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences
- Pharmacology & Pharmacy