Effects of sex and pre-exposure on Δ9-tetrahydrocannabinol (THC) vapor self-administration in rats.

Adult male and female rats self-administered vaporized THC in a sustained manner over several months, adjusting their intake as the response cost and THC concentration changed. Pre-exposure to THC vapor increased subsequent self-administration. Female rats in the THC group responded more than female rats in the vehicle vapor group under increasing response costs. Lower THC doses and THC pre-exposure were critical for establishing the reinforcing effects of THC vapor. The authors propose this as a promising preclinical model for studying cannabis use disorder.

Study at a glance

Abstract

Animal models of cannabinoid self-administration are critical for advancing our understanding of the neurobiology of cannabis use and for developing medications for Cannabis Use Disorder. Use of vapor inhalation models have translational relevance, as the majority of humans who use cannabis do so by inhalation (e.g., smoking, vaporization). Adult male and female Sprague Dawley rats (N = 96, 6-12 per sex/group) were pre-exposed to vaporized THC or vehicle (Veh; 100% propylene glycol). Rats were then trained to self-administer vapor puffs of either THC (50 mg/ml training dose) or Veh under a fixed ratio (FR) 1 schedule. Responding was then assessed under increasing response costs (FR1-5) and different 'doses' (50-200 mg/ml) of THC. As a secondary study aim, we assessed the effects of pre-exposure to THC (or Veh) on self-administration of THC vapor or Veh vapor. There were no differences in responding for THC and Veh vapor under an FR1 schedule. As the FR increased, rats increased their responses for THC, and female rats in the THC group responded more than female rats in the Veh vapor group. When the THC concentration was increased or decreased from the training dose, rats self-administering THC vapor adjusted their responding. THC vapor pre-exposure significantly increased self-administration of THC vapor. Adult male and female rats self-administered THC vapor in a sustained manner across several months. Rats increased their responding to obtain THC vapor as the response cost increased and titrated their THC intake based on the THC concentration available. These data demonstrate sex differences in THC vapor reinforcement and that lower THC doses and THC pre-exposure are critical for engendering the reinforcing effects of THC vapor. This is a promising model of THC vapor self-administration.