A vapourized δ9-tetrahydrocannabinol (δ9-THC) delivery system part I: Development and validation of a pulmonary cannabinoid route of exposure for experimental pharmacology studies in rodents

摘要

Introduction: Most studies evaluating the effects of δ9-tetrahydrocannabinol (δ9-THC) in animal models administer it via a parenteral route (e.g., intraperitoneal (IP) or intravenous injection (IV)), however, the common route of administration for human users is pulmonary (e.g., smoking or vapourizing marijuana). A vapourized δ9-THC delivery system for rodents was developed and used to compare the effects of pulmonary and parenteral δ9-THC administration on blood cannabinoid levels and behaviour. Methods: Sprague-Dawley rats were exposed to pulmonary δ9-THC (1, 5, and 10mg of inhaled vapour) delivered via a Volcano? vapourizing device (Storz and Bickel, Germany) or to parenteral δ9-THC (0.25, 0.5, 1.0, and 1.5mg/kg injected IP). Quantification of δ9-THC and its psychoactive metabolite, 11-hydroxy-δ9-THC (11-OH-δ9-THC), in blood was determined by liquid chromatography/mass spectrometry (LC/MS). In order to verify the potential for the vapourization procedure to produce a robust conditioned place preference (CPP) or conditioned place avoidance CPA, classical conditioning procedures were systematically varied by altering the exposure time (10 or 20min) and number of exposed rats (1 or 2) while maintaining the same vapourization dose (10mg). Results: Blood collected at 20min intervals showed similar dose-dependent and time-dependent changes in δ9-THC and 11-OH-δ9-THC for both pulmonary and parenteral administration of δ9-THC. However, vapourized δ9-THC induced CPP under certain conditions whereas IP-administered δ9-THC induced CPA. Discussion: These results support and extend the limited evidence (e.g., in humans, Naef et al., 2004; in rodents, Niyuhire et al., 2007) that δ9-THC produces qualitatively different effects on behaviour depending upon the route of administration.