Effects of sex and pre-exposure on Δ9-tetrahydrocannabinol (THC) vapor self-administration in rats.
Catherine F Moore, Elise M Weerts
Psychopharmacology May 1, 2026 DOI: 10.1007/s00213-025-06930-8 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Sample size | 96 |
| Population | Adult male and female Sprague Dawley rats |
| Intervention | Vaporized THC |
| Dose | 50 mg/ml training dose, 50-200 mg/ml range |
| Duration | Several months |
| Topics | Cannabis |
| Keywords | Cannabinoids Delta-9-tetrahydrocannabinol Inhalation Preclinical models Reinforcement Self-administration Vapor |
| Key findings | Rats self-administered THC vapor in a sustained manner, titrated their intake based on concentration, and showed sex differences in reinforcement; THC pre-exposure increased subsequent self-administration. |
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.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cites 3
- Sex Differences in Response-Contingent Cannabis Vapor Administration During Adolescence Mediate Enduring Effects on Behavioral Flexibility and Prefrontal Microglia Activation in Rats Cannabis and Cannabinoid Research January 8, 2024
- An intravenous self-administration procedure for assessing the reinforcing effects of hallucinogens in nonhuman primates. Journal of pharmacological and toxicological methods 2016
- Self-administration of delta9-tetrahydrocannabinol (THC) by drug naive squirrel monkeys. Psychopharmacology September 2003