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首页> 外文期刊>Journal of Behavioral and Brain Science >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
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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

机译：＆ 放大器;放大器 ; 德尔塔 ;＆ 安培 ; LT ; SUP ＆ 安培 ; GT ; 9＆ 安培 ; LT ; / SUP ＆ 安培 ; 四氢大麻酚 产生的正 性位置偏爱 小鼠 没有显着的 ＆ 安培 ; LT ; I＆ 安培 ; GT ; 离体 ＆ 安培 ; LT ; I＆ 安培 / ; GT; 对肝芳基胺N-乙酰转移酶活性的影响：对其成瘾责任的影响与异丙酚代谢的影响

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Aim: Δ~(9)-Tetrahydrocannabinol (Δ~(9)-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 Δ~(9)-THC in mice and whether Δ~(9)-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 Δ~(9)-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 Δ~(9)-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 Δ~(9)-THC (0.00 - 162 μM) on the activities of NAT from untreated mice livers were also investigated in-vitro . Results: Δ~(9)-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 Δ~(9)-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). In-vitro NAT evaluations revealed a dose-dependent inhibitory impact of Δ~(9)-THC on NAT activity with an IC50 value of 34.97 ±1.58 μM. Ex-vivo evaluations of livers from Δ~(9)-THC treated mice showed no significant impact on liver NAT enzyme activity. Conclusion: Δ~(9)-THC induced significant conditioned place preference (drug reward) and produced a moderate dose-dependent inhibition on NAT activity in-vitro , but not ex-vivo .
机译：目的：Δ〜（9） - 四氢甘油醛（δ〜（9）-THC）是一个潜在令人上瘾的大麻素。尚未报道其对肝芳基胺N-乙酰转移酶（NAT）活性的影响。本研究研究了δ〜（9）-THC在小鼠中的奖励作用以及δ〜（9）-THC是否对NAT活性的体外产生任何影响。 方法：三十六个瑞士白杀菌随机分配到六组（n = 6）完成了偏置，8周条件的偏好（CPP）范式。选择在预处理下表现出〜80％的黑色室偏好的小鼠。治疗组施用δ〜（9） - 否（0.10,0.50或2.0mg / kg / ml，结论：δ〜（9） - 诱导有效的条件偏好（药物奖励），并在体外对NAT活性依赖性抑制产生中等的剂量依赖性抑制，但不是 ex-体内。

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