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Δ<sup>9</sup>-Tetrahydrocannabinol Produced Positive Place Preference in Mice without Significant <i>Ex-Vivo</i>Effect on Hepatic Arylamine N-Acetyltransferase Activity: Implications for Its Addictive Liability and Absence of Effect on Xenobiotic Metabolism

引用

Journal of Behavioral and Brain Science 2021年第8期11卷 179-192页

作者： Lauriann Young Karen Thaxter Danielle Campbell sheena francis Nicola Laurieri Rupika Delgoda Physiology Section Department of Basic Medical Sciences The University of the West Indies (UWI) Mona Campus Kingston Jamaica Natural Products Institute The University of the West Indies (UWI) Mona Campus Kingston Jamaica Department of Pharmacology Oxford University Oxford England UK

Aim: Δ9-Tetrahydrocannabinol (Δ9-THC) is a potentially addictive cannabinoid. Its impact on the activity of liver arylamine N-Acetyltransferase (NAT) has not been reported. This study investigated the rewarding effects of Δ9-THC in mice and whether Δ9-THC had any impact ex-vivo and in-vitro on NAT activity. Methods: Thirty-six Swiss albinomice randomly assigned to six groups (n = 6) completed a biased, 8-week Conditioned Place Preference (CPP) paradigm. Mice exhibiting ~80% preference for the black chamber at pre-conditioning were selected. Treatment groups were administered Δ9-THC (0.10, 0.50 or 2.0 mg/kg/mL, ip) or amphetamine (AMP, 5.0 mg/kg/mL, ip);while untreated groups (controls) received vehicle solutions (coconut oil or 0.9% saline). Entries and time spent in the white, drug-paired chamber during a 15-min post-conditioning exploration of the CPP apparatus were compared with the pre-conditioning exploratory scores. Livers from Δ9-THC treated and untreated mice were excised and NAT enzyme activity determined ex-vivo using a spectrophotometric assay with p-anisidine as substrate. The impact of varying concentrations of Δ9-THC (0.00 - 162 μM) on the activities of NAT from untreated mice livers were also investigated in-vitro. Results: Δ9-THC treated mice entered and spent significantly more time in the drug-paired CPP chamber (p ≤ 0.05) at post-conditioning vs pre-conditioning (F = 11.22). Mice treated with 2.0 mg/kg Δ9-THC made significantly more entries into the drug-paired chamber (p ≤ 0.05) as compared with their vehicle controls. AMP-treated mice displayed significant (p In-vitro NAT evaluations revealed a dose-dependent inhibitory impact of Δ9-THC on NAT

关键词： Cannabis Marijuana Conditioned Place Preference Addiction Drug Reward

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