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雌性大鼠自行摄取低剂量尼古丁与摄取烟草烟雾提取物中的尼古丁。

Self-administration by female rats of low doses of nicotine alone vs. nicotine in tobacco smoke extract.

机构信息

Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.

Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.

出版信息

Drug Alcohol Depend. 2021 Nov 1;228:109073. doi: 10.1016/j.drugalcdep.2021.109073. Epub 2021 Sep 24.

Abstract

BACKGROUND

Nicotine has reinforcing effects, but there are thousands of other compounds in tobacco, some of which might interact with nicotine reinforcement.

AIMS

This rat study was conducted to determine if nicotine self-administration is altered by co-administration of the complex mixture of compounds in tobacco smoke extract (TSE).

METHODS

Female Sprague-Dawley rats were tested for self-administration of low doses of nicotine (3 or 10 µg/kg/infusion) at three different rates of reinforcement (FR1, FR3 and FR5) over three weeks either alone or together with the complex mixture of tobacco smoke extract (TSE).

RESULTS

Rats self-administering 3 µg/kg/infusion of nicotine alone showed a rapid initiation on an FR1 schedule, but declined with FR5. Rats self-administering nicotine in TSE acquired self-administration more slowly, but increased responding over the course of the study. With 10 µg/kg/infusion rats self-administered significantly more nicotine alone than rats self-administering the same nicotine dose in TSE. Rats self-administering nicotine alone took significantly more infusions with the 10 than the 3 µg/kg/infusion dose, whereas rats self-administering nicotine in TSE did not. Nicotine in TSE led to a significantly greater locomotor hyperactivity at a dose of 0.1 mg/kg compared to rats that received nicotine alone. Rats self-administering nicotine alone had significantly more responding on the active vs. inactive lever, but rats self-administering the same nicotine doses in TSE did not.

CONCLUSIONS

Self-administration of nicotine in a purer form appears to be more clearly discriminated and dose-related than nicotine self-administered in the complex mixture of TSE.

摘要

背景

尼古丁具有强化作用,但烟草中还有数千种其他化合物,其中一些可能与尼古丁的强化作用相互作用。

目的

本项大鼠研究旨在确定烟草烟雾提取物(TSE)中的复杂混合物是否会改变尼古丁的自我给药。

方法

雌性 Sprague-Dawley 大鼠在三周内,分别以三个不同的强化率(FR1、FR3 和 FR5),单独或与烟草烟雾提取物(TSE)的复杂混合物一起,测试低剂量(3 或 10μg/kg/剂量)尼古丁的自我给药情况。

结果

单独给予 3μg/kg/剂量的尼古丁的大鼠在 FR1 方案中迅速开始自我给药,但随着 FR5 的增加而减少。在 TSE 中自我给予尼古丁的大鼠获得自我给药的速度较慢,但在研究过程中反应增加。与单独给予 10μg/kg/剂量的大鼠相比,大鼠在 TSE 中自我给予相同剂量的尼古丁时,自我给药的量明显减少。单独给予尼古丁的大鼠给予 10μg/kg/剂量的剂量明显多于 3μg/kg/剂量,而在 TSE 中自我给予尼古丁的大鼠则没有。与单独给予尼古丁的大鼠相比,给予 0.1mg/kg 剂量 TSE 中的尼古丁导致运动过度活跃的程度显著增加。与单独给予尼古丁的大鼠相比,在 TSE 中自我给予相同剂量尼古丁的大鼠在活动与非活动杠杆上的反应没有显著差异。

结论

与在 TSE 的复杂混合物中自我给予尼古丁相比,以更纯净的形式给予尼古丁似乎更能明确区分且具有剂量相关性。

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