Pharmacokinetic and pharmacodynamic properties of aerosolized ("vaped") THC in adolescent male and female rats.
Pharmacokinetic and pharmacodynamic properties of aerosolized ("vaped") THC in adolescent male and female rats.
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DOI：
10.1007/s00213-021-05976-8
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发表时间：
2021-12
影响因子：
3.4
通讯作者：
Mahler SV
中科院分区：
文献类型：
--
作者：
Ruiz CM;Torrens A;Lallai V;Castillo E;Manca L;Martinez MX;Justeson DN;Fowler CD;Piomelli D;Mahler SV
Adolescent exposure to Δ9-tetrahydrocannabinol (THC), the psychotropic constituent of cannabis, might affect brain development and in rodent models leads to long-term behavioral and physiological alterations. Yet the basic pharmacology of this drug in adolescent rodents, especially when ingested via ecologically relevant routes like aerosol inhalation, commonly referred to as ‘vaping’, is still poorly characterized. Moreover, sex differences exist in THC metabolism, kinetics and behavioral effects, but these have not been rigorously examined after vapor dosing in adolescents. We investigated the pharmacokinetics and pharmacodynamics of aerosolized THC (30 min inhalation exposure, 25 or 100 mg/ml) in adolescent Wistar rats of both sexes. Liquid chromatography/mass spectrometry analysis of THC and its major metabolites was conducted on blood plasma and brain tissue at 5, 30, 60, and 120 min following a 30 min aerosol dosing session. Effects on activity in a novel environment for 120 min after aerosol, and temperature, were measured in separate rats. We found sex-dependent differences in the pharmacokinetics of THC and its active (11-OH-THC) and inactive (11-COOH-THC) metabolites in blood and brain, along with dose- and sex-dependent effects on anxiety-like and exploratory behaviors, namely greater 11-OH-THC levels accompanied by greater behavioral effects in females at the low dose, but similar hypothermic effects in both sexes at the high dose. These results provide a benchmark for dosing adolescent rats with aerosolized (or ‘vaped’) THC, which could facilitate adoption by other labs of this potentially human-relevant THC exposure model to understand cannabis effects on the developing brain.
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DOI：
10.1016/j.pnpbp.2020.110141
发表时间：
2021-03-02
影响因子：
5.6
作者：
Hamidullah, Shahnaza;Lutelmowski, Claudia D.;Khokhar, Jibran Y.
通讯作者：
Khokhar, Jibran Y.
影响因子：
7.6
作者：
Kruse, Lauren C.;Cao, Jessica K.;Clark, Jeremy J.
通讯作者：
Clark, Jeremy J.
影响因子：
2.3
作者：
Friedman, Amy L.;Meurice, Claire;Jutkiewicz, Emily M.
通讯作者：
Jutkiewicz, Emily M.
影响因子：
4.8
作者：
Gomes, Felipe V.;Guimaraes, Francisco S.;Grace, Anthony A.
通讯作者：
Grace, Anthony A.
影响因子：
5.4
作者：
Gibula-Tarlowska, Ewa;Wydra, Karolina;Kotlinska, Jolanta H.
通讯作者：
Kotlinska, Jolanta H.