TY - JOUR PY - 2014// TI - A Vapourized Δ(9)-Tetrahydrocannabinol (Δ(9)-THC) Delivery System Part I: Development and Validation of a Pulmonary Cannabinoid Route of Exposure for Experimental Pharmacology Studies in Rodents JO - Journal of pharmacological and toxicological methods A1 - Manwell, Laurie A. A1 - Charchoglyan, Armen A1 - Brewer, Dyanne A1 - Matthews, Brittany A. A1 - Heipel, Heather A1 - Mallet, Paul E. SP - 120 EP - 127 VL - 70 IS - 1 N2 - INTRODUCTION:: Most studies evaluating the effects of Δ(9)-tetrahydrocannabinol (Δ(9)-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 Δ(9)-THC delivery system for rodents was developed and used to compare the effects of pulmonary and parenteral Δ(9)-THC administration on blood cannabinoid levels and behaviour.

METHODS: Sprague-Dawley rats were exposed to pulmonary Δ(9)-THC (1, 5, and 10 mg of inhaled vapour) delivered via a Volcano® vapourizing device (Storz and Bickel, Germany) or to parenteral Δ(9)-THC (0.25, 0.5, 1.0, and 1.5 mg/kg injected IP). Quantification of Δ(9)-THC and its psychoactive metabolite, 11-hydroxy-Δ(9)-THC (11-OH-Δ(9)-THC), in blood were 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 20 min) and number of exposed rats (1 or 2) while maintaining the same vapourization dose (10 mg).

RESULTS: Blood collected at 20 min intervals showed similar dose-dependent and time-dependent changes in Δ(9)-THC and 11-OH-Δ(9)-THC for both pulmonary and parenteral administration of Δ(9)-THC. However, vapourized Δ(9)-THC induced CPP under certain conditions whereas IP-administered Δ(9)-THC induced CPA.

CONCLUSION: These results support and extend the limited evidence (e.g., Naef et al., 2003, 2004; Niyuhire et al., 2007a) that Δ(9)-THC produces qualitatively different effects on behaviour depending upon the route of administration.

Language: en

LA - en SN - 1056-8719 UR - http://dx.doi.org/10.1016/j.vascn.2014.06.006 ID - ref1 ER -