# THC induced similar physiological effects on HIV transgenic rats and their controls without affecting HIV-induced deficits in effortful motivation

## TL;DR

THC had similar physiological effects in HIV transgenic rats and controls, but did not worsen HIV-related motivation deficits.

## Contribution

Demonstrated that THC does not exacerbate HIV-induced motivational deficits in transgenic rats.

## Key findings

- THC reduced nociception, temperature, and locomotor activity across genotypes.
- HIV-1tg rats showed motivational deficits compared to F344 controls but not WT controls.
- Acute THC reduced motivation in rats, but chronic treatment had no effect.

## Abstract

Cannabinoids have proven to useful for attenuating adverse effects of HIV. People living with HIV use cannabis at higher rates, with evidence suggesting it alleviates physiological symptoms such as nausea, loss of appetite, etc.. Cannabis can alter physiology as well as essential behavioral functions such as motivation. This study investigated the effect of delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, on physiological responses and motivation in HIV-1 transgenic (tg) rats and their controls.

In Experiment 1, adult female and male HIV-1tg (n = 46) rats and their controls (wildtype littermates [WT] and Fischer344 [F344] rats; n = 87) were tested for acute THC-induced (0, 0.3, 3 mg/kg) physiological effects using the cannabinoid tetrad assay: 1) nociception, 2) body temperature, and 3) locomotor and exploratory behavior. In Experiment 2, adult female and male HIV-1tg (n = 58) rats and controls (n = 84) were tested in the Progressive Ratio Breakpoint Task (PRBT) to assess effortful motivation at baseline, after acute THC, then chronic (16 days) THC treatment (0, 0.3, 3 mg/kg). Data collected was analyzed using separate univariate ANOVA test with group (HIV-1tg, WT, F344), drug (0, 0.3, 3 mg/kg THC) and sex (female and male) as fixed factors. Bonferroni adjustments were used to correct for multiple comparisons.

THC (3 mg/kg) reduced nociception, temperature, and locomotor and exploratory activity across genotypes with some sex-dependent effects. Further, HIV-1tg and WT rats showed reduced motivation compared to F344 controls across PRBT testing timepoints. Acute 3 mg/kg THC reduced breakpoints but with no effects after chronic treatment.

Hence, THC produces consistent physiological and motivational across HIV-1tg rats and their controls. Additionally, the HIV-1tg rat exhibited motivational deficits only when compared to the F344 but not WT controls, suggesting careful selections of control groups in future studies.

The online version contains supplementary material available at 10.1186/s42238-025-00383-8.