Δ9-tetrahydrocannabinol (THC) vapor exposure produces conditioned rewarding effects in male and female rats

Abstract

AbstractBackgroundVaping of cannabis and cannabis extracts containing Δ9-tetrahydrocannabinol (THC, the primary psychoactive constituent of cannabis) is on the rise. Development of animal models using vapor exposure is important for increasing our understanding of the rewarding and aversive effects of vaped cannabinoids. Currently there are limited data on the conditioned rewarding effects of THC vapor in rats, and no studies to date examining sex differences.MethodsMale and female Sprague-Dawley rats (N=96; 12 per sex/group) underwent place conditioning after exposure to vaporized THC or vehicle (propylene glycol, PG). THC vapor-conditioned rats received one of three THC vapor exposure amounts (THC Group 1: 5 puffs of 100 mg/ml THC, THC Group 2: 5 puffs of 200 mg/ml THC, or THC Group 3: 10 puffs of 200 mg/ml THC) and matched vehicle vapor (PG) exposure and on alternate days for two sets of 8 daily sessions (16 days total). Vehicle-conditioned rats (Veh Group 0) received only PG vapor exposure each day. Rats were passively administered vapor for 30-min immediately before daily, 30-min conditioning sessions. Untreated rats completed place preference tests after the 8th and 16th conditioning sessions and then testing continued daily until extinction occurred. Following extinction, rats underwent a THC vapor-primed reinstatement session.ResultsMale and female rats showed an exposure-dependent preference for the THC vapor-paired chamber, though sex differences were observed. The lowest THC vapor exposure group tested (THC Group 1) did not produce CPP in males or females. Exposure to the middle condition tested (THC Group 2) resulted in preference for the THC vapor-paired chamber in males, but not females. The highest THC vapor exposure condition tested (THC Group 3) produced place preference in both males and females. Preference for the THC-paired chamber extinguished more quickly in males than in females. Following extinction, THC vapor re-exposure (i.e., drug-prime) did not result in reinstatement of place preference for either sex.ConclusionThis study demonstrated conditioned rewarding effects of THC vapor in both male and female rats, and provides evidence for sex differences in doses of THC vapor that produce CPP and in time to extinction. Conditioned place aversion was not observed at any of the THC vapor exposure amounts tested. These data provide a foundation for future exploration of the conditioned rewarding effects vaporized THC, cannabis and its constituents in preclinical models.