Effects of acute Δ9 -tetrahydrocannabinol on behavior and the endocannabinoid system in HIV-1 Tat transgenic female and male mice
Barkha J. Yadav-Samudrala, Ben L. Gorman, Hailey Dodson, Shreya Ramineni, Diane Wallace, Michelle R Peace, Justin L. Poklis, Wei Jiang, Sylvia Fitting
Research Square December 29, 2022 preprint DOI: 10.21203/rs.3.rs-2401488/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study |
|---|---|
| Population | HIV-1 Tat transgenic mice and Tat-negative control mice, both female and male |
| Intervention | Δ9-tetrahydrocannabinol (THC) |
| Dose | 1, 3, 10 mg/kg |
| Topics | Cannabis |
| Citations | 1 |
| Key points | Acute THC reduced spontaneous nociception, with Tat induction increasing this antinociceptive effect, and produced anxiogenic effects at 10 mg/kg in Tat-negative females and males, with females showing more anxiety-like behavior overall. THC (10 mg/kg) impaired object recognition memory in Tat-negative but not Tat-positive females, without affecting males. The authors indicate these sex- and Tat-dependent behavioral effects may relate to an altered endocannabinoid system. |
Abstract
Abstract Cannabis use is highly prevalent especially among people living with HIV (PLWH). Activation of the anti-inflammatory and neuroprotective endocannabinoid system by phytocannabinoids, i.e. Δ9-tetrahydrocannabinol (THC), has been proposed to reduce HIV symptoms. However, THC’s effects on HIV-associated cognitive impairments are unclear. Using HIV-1 Tat transgenic mice, the current study investigates acute THC effects on various behavioral outcomes and the endocannabinoid system. Minor or no effects of THC doses (1, 3, 10 mg/kg) were noted for body mass, body temperature, locomotor activity, and coordination, but spontaneous nociception was significantly decreased, with Tat induction increasing antinociceptive THC effects. Anxiogenic effects of THC (10 mg/kg) were demonstrated in Tat(−) females and males compared to vehicle-treated mice, with overall increased anxiety-like behavior in females compared to males. Object recognition memory was diminished by acute THC (10 mg/kg) injections in Tat(−) but not Tat(+) females, without affecting males. For the endocannabinoid system and related lipids, no effects were noted for acute THC, but female sex and Tat induction was associated with elevated 2-AG, AEA, AA, CB1R, CB2R, FAAH and/or MAGL expression in various CNS regions. Further, females demonstrated higher AEA levels compared to males in most CNS structures, and AEA levels in the prefrontal cortex of Tat(+) females were negatively associated with recognition memory. Overall, findings indicate that acute THC exposure exerts differential effects on behavior in the context of neuroHIV dependent on sex, potentially due to an altered endocannabinoid system, which may be of relevance in view of potential cannabis-based treatment options for PLWH.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cites 15
- Sex differences in acute cannabis effects revisited: Results from two randomized, controlled trials Addiction Biology December 22, 2021
- Effects of ∆9-tetrahydrocannabinol on aversive memories and anxiety: a review from human studies. BMC Psychiatry August 26, 2020
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- Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: A systematic review and meta-analysis The Lancet Psychiatry October 28, 2019
and 10 more in the library