巴氯芬预防尼古丁戒断时躯体症状和神经化学变化的能力。
Ability of baclofen to prevent somatic manifestations and neurochemical changes during nicotine withdrawal.
机构信息
Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Piso, Buenos Aires C1113AAD, Argentina.
出版信息
Drug Alcohol Depend. 2011 Dec 1;119(1-2):e5-12. doi: 10.1016/j.drugalcdep.2011.05.017. Epub 2011 Jul 5.
BACKGROUND
Nicotine (NIC), the major active component of tobacco, is critical in the maintenance of the smoking habit. The aims of the present study were to analyze the behavioural and neurochemical variations during NIC withdrawal syndrome in mice, and whether they are prevented with baclofen (BAC, GABA(B) receptor agonist).
METHODS
Swiss-Webster albino mice received NIC (2.5 mg/kg, s.c.) 4 times daily, for 7 consecutive days. On day 8 (the day of the experiment), NIC-treated mice received the nicotine antagonist mecamylamine (MEC, 2 mg/kg, i.p.) 1h after the last dose of NIC. A second group of dependent mice received BAC (2mg/kg, i.p.) before MEC-precipitated abstinence. The somatic signs were measured for 30 min. Dopamine (DA), serotonin (5-hydroxytryptamine; 5-HT) and its metabolites concentrations were determined by HPLC in the striatum, cortex and hippocampus.
RESULTS
The global score was greater in the abstinent group compared to the control group. Moreover, the global score time course showed a higher increase at 10 min compared to the global score at 5 min or 30 min after MEC-precipitated NIC withdrawal. In addition, the global score was attenuated by BAC. The DA and dihydroxyphenyl acetic acid (DOPAC) cortical levels decreased in the abstinent group, while BAC reestablished these levels 10 min after NIC withdrawal. Furthermore, DA and 5-HT striatal levels decreased during NIC withdrawal, and BAC reverted this decrease.
CONCLUSION
In conclusion, the prevention of NIC withdrawal signs by BAC could be related to changes in dopaminergic and serotonergic activity.
背景
尼古丁（NIC）是烟草中的主要活性成分，对维持吸烟习惯至关重要。本研究旨在分析尼古丁戒断综合征期间小鼠的行为和神经化学变化，以及巴氯芬（BAC，GABA（B）受体激动剂）是否可以预防这些变化。
方法
瑞士-韦伯斯特白化小鼠每天接受 4 次尼古丁（2.5mg/kg，皮下注射），连续 7 天。在第 8 天（实验当天），尼古丁处理的小鼠在最后一次接受尼古丁后 1 小时接受尼古丁拮抗剂美加明（MEC，2mg/kg，腹腔注射）。第二组依赖小鼠在 MEC 诱发的戒断前接受 BAC（2mg/kg，腹腔注射）。测量 30 分钟的躯体症状。通过 HPLC 在纹状体、皮质和海马中测定多巴胺（DA）、5-羟色胺（5-HT）及其代谢物的浓度。
结果
与对照组相比，戒断组的总分更高。此外，总分时间进程显示，在 MEC 诱发的 NIC 戒断后 10 分钟的总分比 5 分钟或 30 分钟的总分增加更高。此外，BAC 减弱了总分。皮质中的 DA 和二羟苯乙酸（DOPAC）水平在戒断组中降低，而 BAC 在 NIC 戒断后 10 分钟恢复了这些水平。此外，DA 和 5-HT 纹状体水平在 NIC 戒断期间降低，而 BAC 逆转了这种降低。
结论
总之，BAC 预防 NIC 戒断症状可能与多巴胺能和 5-羟色胺能活性的变化有关。
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