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HIV and cocaine exposure disrupt stress systems and cocaine seeking
Thesis

HIV and cocaine exposure disrupt stress systems and cocaine seeking

Kylie Volksdorf
Master of Science (M.S.), Drexel University
Apr 2026
DOI:
https://doi.org/10.17918/00011506
pdf
Volksdorf_Kylie_202611.24 MB
PDF Embargoed Access, Embargo ends: 31 Jul 2028

Abstract

Cocaine use disorder (CUD) is common among people living with HIV (PLWH), and relapse remains a challenge in the treatment of CUD. Stress is a major factor that can drive drug craving and promote relapse. The glucocorticoid system plays an important role in regulating the response to stress, and both HIV infection and cocaine exposure are known to disrupt this stress system. However, the mechanisms through which these factors interact to influence relapse vulnerability remain unclear. Astrocytic glucocorticoid receptors (GRs) are particularly sensitive to stress and are dysregulated by both HIV infection and drug exposure. Moreover, astrocytic signaling in the nucleus accumbens (NAc) has been implicated in relapse-related behaviors, suggesting that astrocytic GR may be important regulators of the stress response in HIV infection and drug use. To better understand the interaction of HIV and cocaine exposure on stress systems and cocaine seeking, we used the EcoHIV mouse model to investigate the interactive effects of EcoHIV and cocaine exposure on astrocytic GR expression in the NAc, and the impact of EcoHIV on stress + cocaine-induced reinstatement of cocaine seeking. In experiment 1, mice underwent sub-chronic cocaine exposure followed by a two week abstinence period. Mice were then subjected to forced swim stress or served as no stress controls prior to perfusion to assess astrocytic GR expression in the NAc via astrocytic marker, S100b, and GR immunofluorescence. Our findings demonstrate that EcoHIV infection downregulated astrocytic S100b expression without altering S100b-positive cells expressing GR in the NAc. In experiment 2, mice underwent cocaine conditioned place preference (CPP), extinction, and stress + cocaine-induced reinstatement of cocaine seeking, followed by S100b and GR immunofluorescence analysis. EcoHIV did not significantly impact CPP, extinction, or reinstatement behavior. However, EcoHIV increased astrocytic S100b expression in a sex-specific manner in the NAc of female mice following reinstatement, without altering S100b-positive cells expressing GR. These findings suggest that EcoHIV infection dysregulated astrocytic S100b expression in the NAc, with limited effects on S100b-positive cells expressing GR and relapse-related behaviors. These data highlight astrocytes in stress-related pathways as potential targets for further identifying mechanisms of relapse vulnerability in people living with HIV and cocaine use disorder.

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