| Title: |
Escalated (Dependent) Oxycodone Self-Administration Is Associated with Cognitive Impairment and Transcriptional Evidence of Neurodegeneration in Human Immunodeficiency Virus (HIV) Transgenic Rats |
| Authors: |
Fu Y.; Lorrai I.; Zorman B.; Mercatelli D.; Shankula C.; Gaytan J. M.; Lefebvre C.; de Guglielmo G.; Kim H. R.; Sumazin P.; Giorgi F. M.; Repunte-Canonigo V.; Sanna P. P. |
| Contributors: |
Fu Y.; Lorrai I.; Zorman B.; Mercatelli D.; Shankula C.; Gaytan J.M.; Lefebvre C.; de Guglielmo G.; Kim H.R.; Sumazin P.; Giorgi F.M.; Repunte-Canonigo V.; Sanna P.P. |
| Publication Year: |
2022 |
| Subject Terms: |
AIDS; cognitive impairment; neuroHIV; neuroinflammation; Analgesics; Opioid; Animal; Glucocorticoid; HIV; Human; Oxycodone; Rat; Rats; Transgenic; Cognitive Dysfunction; HIV Infections; socio; psy |
| Description: |
Substance use disorder is associated with accelerated disease progression in people with human immunodeficiency virus (HIV; PWH). Problem opioid use, including high-dose opioid therapy, prescription drug misuse, and opioid abuse, is high and increasing in the PWH population. Oxycodone is a broadly prescribed opioid in both the general population and PWH. Here, we allowed HIV transgenic (Tg) rats and wildtype (WT) littermates to intravenously self-administer oxycodone under short-access (ShA) conditions, which led to moderate, stable, “recreational”-like levels of drug intake, or under long-access (LgA) conditions, which led to escalated (dependent) drug intake. HIV Tg rats with histories of oxycodone self-administration under LgA conditions exhibited significant impairment in memory performance in the novel object recognition (NOR) paradigm. RNA-sequencing expression profiling of the medial prefrontal cortex (mPFC) in HIV Tg rats that self-administered oxycodone under ShA conditions exhibited greater transcriptional evidence of inflammation than WT rats that self-administered oxycodone under the same conditions. HIV Tg rats that self-administered oxycodone under LgA conditions exhibited transcriptional evidence of an increase in neuronal injury and neurodegeneration compared with WT rats under the same conditions. Gene expression analysis indicated that glucocorticoid-dependent adaptations contributed to the gene expression effects of oxycodone self-administration. Overall, the present results indicate that a history of opioid intake promotes neuroinflammation and glucocorticoid dysregulation, and excessive opioid intake is associated with neurotoxicity and cognitive impairment in HIV Tg rats. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://hdl.handle.net/11585/884255 |
| Availability: |
https://hdl.handle.net/11585/884255 |
| Rights: |
undefined |
| Accession Number: |
edsbas.CE6CF601 |
| Database: |
BASE |