Δ9-Tetrahydrocannabinol Vapor Exposure Produces Conditioned Place Preference in Male and Female Rats

Abstract

Background: The use of place conditioning procedures and drug vapor exposure models can increase our understanding of the rewarding and aversive effects of vaped cannabis products. Currently there are limited data on the conditioned rewarding effects of vaporized Δ⁹-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis in rats, and no studies to date examining sex differences. Methods: Male and female Sprague-Dawley rats (N=96; 12 per sex/group) underwent place conditioning sessions immediately after exposure to THC or vehicle (propylene glycol [PG]) vapor. Locomotor activity was measured by beam breaks during conditioning sessions. THC vapor-conditioned rats received one of three THC vapor exposure amounts (low: 5 puffs of 100 mg/mL THC, medium: 5 puffs of 200 mg/mL THC, or high: 10 puffs of 200 mg/mL THC) and matched vehicle vapor (PG) exposure on alternate days for 16 daily sessions. A "no THC" control group of vehicle-conditioned rats received only PG vapor exposure each day. After the 8th and 16th conditioning sessions, untreated rats were tested for conditioned place preference (CPP) or aversion (CPA). Next, extinction tests and a THC vapor-primed reinstatement test were conducted. Results: THC vapor produced CPP and locomotor effects in an exposure dependent manner, and some sex differences were observed. Low THC vapor exposure did not produce CPP in males or females. Medium THC vapor exposure produced CPP in males, but not females. High THC vapor exposure produced CPP in both males and females. Medium and high THC vapor exposure amounts produced hyperactivity in female rats, but not male rats. CPP was more resistant to extinction in females than males. THC vapor reexposure (i.e., drug-prime) after extinction did not result in reinstatement of CPP for either sex. Conclusion: This study demonstrates conditioned rewarding effects of THC vapor in both male and female rats and provides evidence for sex differences in amounts of THC vapor that produce CPP and in time to extinction. CPA was not observed at any of the THC vapor exposure amounts tested. These data provide a foundation for future exploration of the conditioned effects of cannabis constituents and extracts using vapor exposure models.

Keywords: THC; cannabis; conditioned place preference; reward; vapor exposure.

FIG. 1.

Change in preference score across successive place preference tests. Data shown are group means (±SEM) for post-tests 1 and 2, conducted after each conditioning days 1–8 and 9–16, respectively. An asterisk represents a place preference (CPP score post-test—CPP score pretest >0; p>0.05, determined by a one-sample t-test). CPP, conditioned place preference; SEM, standard error of the mean; THC, Δ-tetrahydrocannabinol.

FIG. 2.

Change in preference score across successive extinction tests. Data shown are group means (±SEM). An asterisk represents a place preference (CPP score post-test—CPP score pretest >0; p>0.05, determined by a one-sample t-test).

FIG. 3.

Distance traveled on conditioning days 1, 7, and 15. Asterisks denote significant post hoc differences between a THC group compared to the vehicle (“no THC”) vapor control group on that day; dollar signs denote significant post hoc sex differences on that day. Plus signs denote differences from day 1 for that group (p's<0.05).

FIG. 4.

Levels of THC, 11-OH-THC, and THC-COOH in plasma of rats after acute exposure to medium and high THC vapor. 11-OH-THC, 11-hydroxy-Δ-tetrahydrocannabinol, THC-COOH, 11-Nor-9-carboxy-Δ-tetrahydrocannabinol.