HIV-1 Tat Protein Promotes Neuroendocrine Dysfunction Concurrent with the Potentiation of Oxycodone’s Psychomotor Effects in Female Mice
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 t...
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MDPI AG
2021-04-01
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| Online Access: | https://www.mdpi.com/1999-4915/13/5/813 |
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| author | Mohammed F. Salahuddin Fakhri Mahdi Suresh P. Sulochana Jason J. Paris |
| author_facet | Mohammed F. Salahuddin Fakhri Mahdi Suresh P. Sulochana Jason J. Paris |
| author_sort | Mohammed F. Salahuddin |
| collection | DOAJ |
| description | 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 contributes to Tat-mediated interactions with oxycodone, an opioid often prescribed to HIV patients, in females. Female mice that conditionally-expressed the Tat<sub>1–86</sub> protein [Tat(+) mice] or their counterparts 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 corticotropin-releasing factor receptors (CRF-R) pharmacologically inhibited. Some mice were ovariectomized (OVX). As seen previously in males, Tat elevated basal corticosterone levels and potentiated 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. |
| first_indexed | 2024-03-10T11:47:20Z |
| format | Article |
| id | doaj.art-985e965e51ce46a6a84b91ef9c510c30 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T11:47:20Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-985e965e51ce46a6a84b91ef9c510c302023-11-21T18:00:02ZengMDPI AGViruses1999-49152021-04-0113581310.3390/v13050813HIV-1 Tat Protein Promotes Neuroendocrine Dysfunction Concurrent with the Potentiation of Oxycodone’s Psychomotor Effects in Female MiceMohammed F. Salahuddin0Fakhri Mahdi1Suresh P. Sulochana2Jason J. Paris3Department of BioMolecular Sciences, University of Mississippi School of Pharmacy, Oxford, MS 38677-1848, USADepartment of BioMolecular Sciences, University of Mississippi School of Pharmacy, Oxford, MS 38677-1848, USADepartment of Pharmaceutics and Drug Delivery, University of Mississippi School of Pharmacy, Oxford, MS 38677-1848, USADepartment of BioMolecular Sciences, University of Mississippi School of Pharmacy, Oxford, MS 38677-1848, USAHuman 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 contributes to Tat-mediated interactions with oxycodone, an opioid often prescribed to HIV patients, in females. Female mice that conditionally-expressed the Tat<sub>1–86</sub> protein [Tat(+) mice] or their counterparts 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 corticotropin-releasing factor receptors (CRF-R) pharmacologically inhibited. Some mice were ovariectomized (OVX). As seen previously in males, Tat elevated basal corticosterone levels and potentiated 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.https://www.mdpi.com/1999-4915/13/5/813antalarminhypothalamic-pituitary-adrenal axisovariectomyopioidsmifepristone (RU-486)trans-activator of transcription |
| spellingShingle | Mohammed F. Salahuddin Fakhri Mahdi Suresh P. Sulochana Jason J. Paris HIV-1 Tat Protein Promotes Neuroendocrine Dysfunction Concurrent with the Potentiation of Oxycodone’s Psychomotor Effects in Female Mice Viruses antalarmin hypothalamic-pituitary-adrenal axis ovariectomy opioids mifepristone (RU-486) trans-activator of transcription |
| title | HIV-1 Tat Protein Promotes Neuroendocrine Dysfunction Concurrent with the Potentiation of Oxycodone’s Psychomotor Effects in Female Mice |
| title_full | HIV-1 Tat Protein Promotes Neuroendocrine Dysfunction Concurrent with the Potentiation of Oxycodone’s Psychomotor Effects in Female Mice |
| title_fullStr | HIV-1 Tat Protein Promotes Neuroendocrine Dysfunction Concurrent with the Potentiation of Oxycodone’s Psychomotor Effects in Female Mice |
| title_full_unstemmed | HIV-1 Tat Protein Promotes Neuroendocrine Dysfunction Concurrent with the Potentiation of Oxycodone’s Psychomotor Effects in Female Mice |
| title_short | HIV-1 Tat Protein Promotes Neuroendocrine Dysfunction Concurrent with the Potentiation of Oxycodone’s Psychomotor Effects in Female Mice |
| title_sort | hiv 1 tat protein promotes neuroendocrine dysfunction concurrent with the potentiation of oxycodone s psychomotor effects in female mice |
| topic | antalarmin hypothalamic-pituitary-adrenal axis ovariectomy opioids mifepristone (RU-486) trans-activator of transcription |
| url | https://www.mdpi.com/1999-4915/13/5/813 |
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