Faculty and Student Publications
Document Type
Article
Publication Date
5-1-2021
Abstract
Human immunodeficiency virus (HIV) is associated with neuroendocrine dysfunction which may contribute to co-morbid stress-sensitive disorders. The hypothalamic-pituitary-adrenal (HPA) or-gonadal (HPG) axes are perturbed in up to 50% of HIV patients. The mechanisms are not known, but we have found the HIV-1 trans-activator of transcription (Tat) protein to recapitulate the clinical phenotype in male mice. We hypothesized that HPA and/or HPG dysregulation contrib-utes to Tat-mediated interactions with oxycodone, an opioid often prescribed to HIV patients, in females. Female mice that conditionally-expressed the Tat1–86 protein [Tat(+) mice] or their counter-parts that did not [Tat(−) control mice] were exposed to forced swim stress (or not) and behaviorally-assessed for motor and anxiety-like behavior. Some mice had glucocorticoid receptors (GR) or cor-ticotropin-releasing factor receptors (CRF-R) pharmacologically inhibited. Some mice were ovari-ectomized (OVX). As seen previously in males, Tat elevated basal corticosterone levels and poten-tiated oxycodone’s psychomotor activity in females. Unlike males, females did not demonstrate adrenal insufficiency and oxycodone potentiation was not regulated by GRs or CRF-Rs. Rather OVX attenuated Tat/oxycodone interactions. Either Tat or oxycodone increased anxiety-like behavior and their combination increased hypothalamic allopregnanolone. OVX increased basal hypothalamic allopregnanolone and obviated Tat or oxycodone-mediated fluctuations. Together, these data provide further evidence for Tat-mediated dysregulation of the HPA axis and reveal the importance of HPG axis regulation in females. HPA/HPG disruption may contribute vulnerability to affective and substance use disorders.
Relational Format
journal article
Recommended Citation
Salahuddin, M.F.; Mahdi, F.; Sulochana, S.P.; Paris, J.J. HIV-1 Tat Protein Promotes Neuroendocrine Dysfunction Concurrent with the Potentiation of Oxycodone’s Psychomotor Effects in Female Mice. Viruses 2021, 13, 813. https://doi.org/10.3390/v13050813
DOI
10.3390/v13050813
Accessibility Status
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