EFFECTS OF ACUTE THC CHALLENGE ON BEHAVIOR AND NEUROINFLAMMATION IN HIV-1 TG26 MICE VARY BASED ON HIV STATUS, CHRONIC THC HISTORY, AND SEX

Δ9-tetrahydrocannabinol (THC) has been studied for its neuroprotective benefits and its ability to improve HIV-1-related symptoms in clinical and preclinical models. Research has demonstrated THC’s antinociceptive, hypothermic, and anxiolytic effects; however, chronic THC administration may result in tolerance to these effects following acute administration of THC, and HIV status may further influence these effects. Thus, the present study investigated the effects of an acute THC challenge after chronic THC exposure on behavioral and neuroinflammatory measures using the HIV-1 Tg26 neuroHIV mouse model. HIV-1 Tg26 transgenic (Tg26+/−, n=32(16f)) mice and their control littermates (Tg26−/−, n=31(16f)) received subcutaneous injections of vehicle solution or THC (3mg/kg), once a day, 5 days per week, for 90 days. After a 7-day drug-free period, all mice were given a high dose of THC (10mg/kg; intraperitoneally), and behavioral and neuroinflammatory measures were collected. Results suggest that female mice may develop tolerance to some chronic THC effects and that tolerance development may depend on HIV genotype.