Δ⁹-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  

作　　者：Lauriann Young Karen Thaxter Danielle Campbell Sheena Francis Nicola Laurieri Rupika Delgoda 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)

机构地区：[1]Physiology Section, Department of Basic Medical Sciences, The University of the West Indies (UWI), Mona Campus, Kingston, Jamaica [2]Natural Products Institute, The University of the West Indies (UWI), Mona Campus, Kingston, Jamaica [3]Department of Pharmacology, Oxford University, Oxford, England, UK

出　　处：《Journal of Behavioral and Brain Science》2021年第8期179-192,共14页行为与脑科学期刊（英文）

摘　　要：<b>Aim:</b> 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 <i>ex-vivo</i> and <i>in-vitro</i> on NAT activity. <b>Methods:</b> 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, <i>ip</i>) or amphetamine (AMP, 5.0 mg/kg/mL, <i>ip</i>);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 <i>ex-vivo</i> 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 <i>in-vitro</i>. <b>Results:</b> 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 < 0.001) increases in both entries and time spent in the drug-paired chamber at post-conditioning (positive place preference). <i>In-vitro</i> NAT evaluations revealed a dose-dependent inhibitory impact of Δ⁹-THC on NAT activity with an IC50 value of 34<b>Aim:</b> 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 <i>ex-vivo</i> and <i>in-vitro</i> on NAT activity. <b>Methods:</b> 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, <i>ip</i>) or amphetamine (AMP, 5.0 mg/kg/mL, <i>ip</i>);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 <i>ex-vivo</i> 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 <i>in-vitro</i>. <b>Results:</b> 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 < 0.001) increases in both entries and time spent in the drug-paired chamber at post-conditioning (positive place preference). <i>In-vitro</i> NAT evaluations revealed a dose-dependent inhibitory impact of Δ⁹-THC on NAT activity with an IC50 value of 34

关 键 词：CANNABIS Marijuana Conditioned Place Preference Addiction Drug Reward 

分 类 号：TP3[自动化与计算机技术—计算机科学与技术]