Appetitive, antinociceptive, and hypothermic effects of vaped and injected Δ-9-tetrahydrocannabinol (THC) in rats: exposure and dose-effect comparisons by strain and sex

• Published in: Pharmacology, biochemistry and behavior Vol. 202; p. 173116
• Main Authors: Moore, Catherine F., Davis, Catherine M., Harvey, Eric L., Taffe, Michael A., Weerts, Elise M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2021
• Subjects: Administration, Inhalation; Analgesics - administration & dosage; Analgesics - blood; Analgesics - chemistry; Animals; Appetite; Appetite - drug effects; Behavior, Animal - drug effects; Body Temperature - drug effects; Cannabinoids; Dose-Response Relationship, Drug; Dronabinol - administration & dosage; Dronabinol - blood; Dronabinol - chemistry; Female; Hypothermia; Hypothermia - chemically induced; Injections, Intraperitoneal; Male; Nociception; Nociception - drug effects; Rats; Rats, Sprague-Dawley; Rats, Wistar; Sex Factors; THC; Vapor exposure; Volatilization; Appetite; Nociception; Vapor exposure; PR; Cannabinoids; TW; MPE; IP; FR; THC; Hypothermia
• ISSN: 0091-3057; 1873-5177; 1873-5177
• DOI: 10.1016/j.pbb.2021.173116

Advances in drug vapor exposure systems have enabled evaluation of Δ-9-tetrahydrocannabinol (THC) vapor effects in laboratory animals. The purpose of this study was to 1) establish a range of parameters of THC vapor exposure in rats sufficient to produce a behavioral dose-effect curve in a battery of tasks sensitive to THC; and 2) to investigate sex differences in the effects of THC vapor exposure and THC injection (intraperitoneal, IP) on these behaviors in two strains of outbred rats. Male and female Sprague Dawley and Wistar rats (N = 22, 5–6/sex per group) received THC via passive vapor exposure (200 mg/mL; 5 conditions) and IP injection (1–20 mg/kg) in a within subject design. The effects of vaped and injected THC on appetite was determined using progressive ratio responding for food pellets. THC effects on nociception, measured using the tail withdrawal assay, and body temperature were also assessed during a 5-h test period for evaluation of time course of effects. Plasma THC concentrations were assessed after THC vapor and 10 mg/kg IP THC. THC vapor produced exposure-related increases and decreases in motivation to obtain food under the progressive ratio schedule. IP THC (3–20 mg/kg) reduced breakpoints. Vaped and injected THC produced exposure and dose-dependent antinociception and hypothermia. Sex and strain differences in THC effects were also observed. Plasma THC concentrations were higher after 10 mg/kg IP THC (152 ng/mL) compared to the highest vapor exposure condition tested (38 ng/mL), but magnitude of behavioral effects were comparable. THC vapor exposure produced reliable, dose orderly effects on food-maintained behavior, nociception, and body temperature that are comparable to effects of IP THC, although there were differences in the time course of behavioral outcomes. •This study characterized THC vapor effects in two strains of male and female rats.•A range of THC vapor conditions were used to characterize a dose-effect curve.•THC produced orderly effects on appetitive behavior, nociception, and temperature.•Time course of effects varied with respect to route of administration (vapor, IP).•Sex and strain differences were observed in response to THC effects.