Sienkiewicz-Jarosz Halina, Członkowska Agnieszka I, Lehner Małgorzata, Maciejak Piotr, Siemiatkowski Marek, Szyndler Janusz, Wisłowska Aleksandra, Zienowicz Małgorzata, Bidziński Andrzej, Kostowski Wojciech, Płaźnik Adam
Department of Neurology, Institute of Psychiatry and Neurology, Sobieskiego 9, PL 02-957 Warszawa, Poland.
Pol J Pharmacol. 2003 Mar-Apr;55(2):165-70.
It was proposed that chronic nicotine treatment may induce adaptive changes in GABAA receptors, thus leading to the attenuation of a GABAergic inhibition of dopaminergic neurons. This putative mechanism might underlie the sensitization to nicotine-induced increase in locomotor activity and dopamine metabolism; i.e. phenomena highly significant to the dependence-producing effects of this psychostimulant. To test this hypothesis, in the present study we have analyzed the influence of acute and repeated treatment of rats with nicotine on the binding of a highly selective and competitive GABAA receptor agonist, [3H]-muscimol. The binding was investigated by autoradiography in different brain cortical structures. It was found that nicotine given at the dose stimulating locomotor activity (0.6 mg/kg, sc), markedly increased striatal HVA concentration in the group of animals chronically pretreated (for 6 days) with this psychostimulant. Neither acute nor repeated nicotine administration changed in a significant way the [3H]-muscimol binding to brain cortical structures. Thus, the hypothesis about the role of adaptive changes in GABAA receptors in the enhancement of the biochemical and behavioral effects of nicotine was not confirmed.
有人提出，长期尼古丁治疗可能会诱导GABAA受体发生适应性变化，从而导致对多巴胺能神经元的GABA能抑制作用减弱。这种假定的机制可能是对尼古丁诱导的运动活动增加和多巴胺代谢敏感化的基础；也就是说，这些现象对这种精神兴奋剂的致依赖作用具有高度重要性。为了验证这一假设，在本研究中，我们分析了尼古丁对大鼠进行急性和重复处理后，对一种高度选择性和竞争性的GABAA受体激动剂[3H]-蝇蕈醇结合的影响。通过放射自显影术在不同的脑皮质结构中研究了这种结合。结果发现，以刺激运动活动的剂量（0.6mg/kg，皮下注射）给予尼古丁时，在长期（6天）用这种精神兴奋剂预处理的动物组中，纹状体HVA浓度显著增加。急性或重复给予尼古丁均未显著改变[3H]-蝇蕈醇与脑皮质结构的结合。因此，关于GABAA受体适应性变化在增强尼古丁生化和行为效应中作用的假设未得到证实。
