Schilström Björn, Rawal Nina, Mameli-Engvall Monica, Nomikos George G, Svensson Torgny H
Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Int J Neuropsychopharmacol. 2003 Mar;6(1):1-11. doi: 10.1017/S1461145702003188.
Burst firing of dopaminergic neurons has been found to represent a particularly effective means of increasing dopamine release in terminal areas as well as activating immediate early genes in dopaminoceptive cells. Spontaneous burst firing is largely controlled by the level of activation of NMDA receptors in the ventral tegmental area (VTA) as a consequence of glutamate released from afferents arising mainly in the prefrontal cortex. Nicotine has been found to effectively increase burst firing of dopaminergic cells. This effect of nicotine may be due to an alpha 7 nicotinic receptor-mediated presynaptic facilitation of glutamate release in the VTA. By the use of in-vivo single-cell recordings and immunohistochemistry we here evaluated the role of alpha 7 nicotinic receptors in nicotine-induced burst firing of dopamine cells in the VTA and the subsequent activation of immediate early genes in dopaminoceptive target areas. Nicotine (0.5 mg/kg s.c.) was found to increase firing rate and burst firing of dopaminergic neurons. In the presence of methyllycaconitine (MLA, 6.0 mg/kg i.p.) nicotine only increased firing rate. Moreover, in the presence of dihydro-beta-erythroidine (DH beta E, 1.0 mg/kg i.p.), an antagonist at non-alpha 7 nicotinic receptors, nicotine produced an increase in burst firing without increasing the firing rate. Nicotine also increased Fos-like immunoreactivity in dopamine target areas, an effect that was antagonized with MLA but not with DH beta E. Our data suggest that nicotine's augmenting effect on burst firing is, indeed, due to stimulation of alpha 7 nicotinic receptors whereas other nicotinic receptors seem to induce an increase in firing frequency.
已发现多巴胺能神经元的爆发式放电是增加终末区域多巴胺释放以及激活多巴胺感受性细胞中即早基因的一种特别有效的方式。自发爆发式放电在很大程度上受腹侧被盖区（VTA）中NMDA受体激活水平的控制，这是主要起源于前额叶皮质的传入神经释放谷氨酸的结果。已发现尼古丁可有效增加多巴胺能细胞的爆发式放电。尼古丁的这种作用可能是由于α7烟碱受体介导的VTA中谷氨酸释放的突触前易化。通过使用体内单细胞记录和免疫组织化学方法，我们在此评估了α7烟碱受体在尼古丁诱导的VTA中多巴胺细胞爆发式放电以及随后多巴胺感受性靶区域中即早基因激活中的作用。发现尼古丁（0.5mg/kg皮下注射）可增加多巴胺能神经元的放电频率和爆发式放电。在存在甲基lycaconitine（MLA，6.0mg/kg腹腔注射）的情况下，尼古丁仅增加放电频率。此外，在存在二氢-β-刺桐啶（DHβE，1.0mg/kg腹腔注射）（一种非α7烟碱受体拮抗剂）的情况下，尼古丁使爆发式放电增加而不增加放电频率。尼古丁还增加了多巴胺靶区域中Fos样免疫反应性，这种作用可被MLA拮抗，但不能被DHβE拮抗。我们的数据表明，尼古丁对爆发式放电的增强作用确实是由于刺激了α7烟碱受体，而其他烟碱受体似乎诱导放电频率增加。
