Varani Andrés P, Aso Ester, Moutinho Lirane Machado, Maldonado Rafael, Balerio Graciela N
Instituto de Investigaciones Farmacológicas (CONICET), Junín 956 5° Piso, Buenos Aires, C1113AAD, Argentina.
Psychopharmacology (Berl). 2014 Aug;231(15):3031-40. doi: 10.1007/s00213-014-3469-6. Epub 2014 Feb 20.
Nicotine is a major active ingredient in tobacco and plays a major role in tobacco addiction. In rodents, repeated nicotine administration produces behavioral responses related to its addictive properties, such as reinforcing effects and physical dependence.
The aim of the present study was to evaluate the possible role of GABAB receptor in responses induced by repeated nicotine administration in Swiss Webster mice.
Nicotine hydrogen tartrate salt (0.5 mg/kg, s.c.) administration induced rewarding properties in the conditioning place preference test. The GABAB receptor agonist, baclofen (3 mg/kg, i.p.) abolished the rewarding properties induced by nicotine hydrogen tartrate salt (0.5 mg/kg, s.c.). In addition, naloxone-precipitated nicotine withdrawal induced somatic manifestations, anxiety-like effects in the elevated plus maze test and dysphoric manifestations in the conditioned place aversion paradigm. Baclofen (2 and 3 mg/kg, i.p.) prevented the somatic manifestations and the anxiety-like effects associated with naloxone-precipitated nicotine withdrawal but not the dysphoric manifestations.
These results showed that nicotine rewarding properties and negative aspects of nicotine withdrawal, such as anxiety-like effects and somatic manifestations, can be modulated by the GABAB receptor activity. This study now reveals a novel possible application of baclofen to develop new therapeutic strategies to achieve smoking cessation.
尼古丁是烟草中的主要活性成分，在烟草成瘾中起主要作用。在啮齿动物中，反复给予尼古丁会产生与其成瘾特性相关的行为反应，如强化作用和身体依赖性。
本研究的目的是评估GABAB受体在瑞士韦伯斯特小鼠反复给予尼古丁所诱导的反应中的可能作用。
酒石酸氢尼古丁盐（0.5毫克/千克，皮下注射）给药在条件性位置偏爱试验中诱导出奖赏特性。GABAB受体激动剂巴氯芬（3毫克/千克，腹腔注射）消除了酒石酸氢尼古丁盐（0.5毫克/千克，皮下注射）诱导的奖赏特性。此外，纳洛酮诱发的尼古丁戒断在高架十字迷宫试验中诱导出躯体表现、焦虑样效应，在条件性位置厌恶范式中诱导出烦躁不安的表现。巴氯芬（2和3毫克/千克，腹腔注射）预防了与纳洛酮诱发的尼古丁戒断相关的躯体表现和焦虑样效应，但不能预防烦躁不安的表现。
这些结果表明，尼古丁的奖赏特性以及尼古丁戒断的负面效应，如焦虑样效应和躯体表现，可通过GABAB受体活性进行调节。本研究现在揭示了巴氯芬在开发新的戒烟治疗策略方面的一种新的可能应用。
