Effects of acute cannabidiol on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice

Barkha J Yadav-Samudrala; Benjamin L Gorman; Karenna M Barmada; Havilah P Ravula; Caitlin J Huguely; E Diane Wallace; Michelle R Peace; Justin L Poklis; Wei Jiang; Sylvia Fitting

doi:10.3389/fnins.2024.1358555

Effects of acute cannabidiol on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice

Front Neurosci. 2024 Mar 5:18:1358555. doi: 10.3389/fnins.2024.1358555. eCollection 2024.

Affiliations

¹ Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
² Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
³ Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, United States.
⁴ Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, United States.
⁵ Division of Infectious Diseases, Department of Medicine, Medical University of South Carolina, Charleston, SC, United States.

Abstract

Background: Some evidence suggests that cannabidiol (CBD) has potential to help alleviate HIV symptoms due to its antioxidant and anti-inflammatory properties. Here we examined acute CBD effects on various behaviors and the endocannabinoid system in HIV Tat transgenic mice.

Methods: Tat transgenic mice (female/male) were injected with CBD (3, 10, 30 mg/kg) and assessed for antinociception, activity, coordination, anxiety-like behavior, and recognition memory. Brains were taken to quantify endocannabinoids, cannabinoid receptors, and cannabinoid catabolic enzymes. Additionally, CBD and metabolite 7-hydroxy-CBD were quantified in the plasma and cortex.

Results: Tat decreased supraspinal-related nociception and locomotion. CBD and sex had little to no effects on any of the behavioral measures. For the endocannabinoid system male sex was associated with elevated concentration of the proinflammatory metabolite arachidonic acid in various CNS regions, including the cerebellum that also showed higher FAAH expression levels for Tat(+) males. GPR55 expression levels in the striatum and cerebellum were higher for females compared to males. CBD metabolism was altered by sex and Tat expression.

Conclusion: Findings indicate that acute CBD effects are not altered by HIV Tat, and acute CBD has no to minimal effects on behavior and the endocannabinoid system.

Keywords: 2-arachidonoylglycerol; FAAH; GPR55; Tat transgenic mice; antinociception; arachidonic acid; cannabidiol.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This research was funded by the National Institute on Drug Abuse (NIDA), R01 DA055523 (SF and WJ), R21 DA041903 (SF), T32 DA007244 (HR), P30 DA033934 (JP), and the Merit Review Award Number CX002422 (WJ) from the United States (U.S.) Department of Veterans Affairs Office of Research and Development (BLR&D) Service.