Teo Min-Yau, van Wyk Michiel, Lin John, Lipski Janusz
Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92-019, Auckland, New Zealand.
Acta Neurobiol Exp (Wars). 2004;64(2):119-30. doi: 10.55782/ane-2004-1498.
Despite resembling each other in many respects, dopaminergic neurons of the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) exhibit dissimilar responses to nicotine in vivo. To investigate this in an in vitro model, the acute effects of nicotine on the firing of SNc and VTA neurons were compared in transverse juvenile rat midbrain sections (300-350 microm) using extracellular recording. Levels of nicotine comparable with those encountered in smokers (0.2-1.0 microM, 3 min) not only increased firing rate, but also evoked prolonged irregular firing, as indicated by the increase in the coefficient of variation of discharge frequencies. Pre- and postsynaptic nicotinic cholinergic receptors (nAChRs) were involved, as both effects persisted, although at an attenuated level, in low Ca2+ / high Mg2+. Only the nicotine-induced elevation of firing rate was sensitive to the glutamate receptor antagonists APV and CNQX, implying that enhanced glutamate release and glutamate receptor activation are involved in the effects of nicotine on discharge frequency but not pattern. Furthermore, nicotine (1.0 microM) exerted a greater increase in the firing frequency of VTA neurons relative to SNc neurons, suggesting that the differential effects on the two populations previously reported in vivo were due to a difference in the postsynaptic nAChR response and/or local synaptic circuits. Low concentrations of nicotine can thus profoundly modulate the activity of dopaminergic mesencephalic neurons through a local action within the ventral midbrain in vitro, and, similarly to in vivo conditions, evoke stronger effects in the VTA.
尽管黑质致密部（SNc）和腹侧被盖区（VTA）的多巴胺能神经元在许多方面彼此相似，但它们在体内对尼古丁的反应却不同。为了在体外模型中研究这一现象，使用细胞外记录技术，在横向的幼年大鼠中脑切片（300 - 350微米）中比较了尼古丁对SNc和VTA神经元放电的急性影响。与吸烟者体内浓度相当的尼古丁水平（0.2 - 1.0微摩尔，3分钟）不仅增加了放电频率，还引发了长时间的不规则放电，放电频率变异系数的增加表明了这一点。突触前和突触后的烟碱型胆碱能受体（nAChRs）都参与其中，因为在低钙/高镁环境下，这两种效应虽然减弱但仍然存在。只有尼古丁诱导的放电频率升高对谷氨酸受体拮抗剂APV和CNQX敏感，这意味着谷氨酸释放增强和谷氨酸受体激活参与了尼古丁对放电频率的影响，但不涉及放电模式。此外，相对于SNc神经元，尼古丁（1.0微摩尔）使VTA神经元的放电频率有更大幅度的增加，这表明先前在体内报道的对这两种神经元群体的不同影响是由于突触后nAChR反应和/或局部突触回路的差异。因此，低浓度的尼古丁可以通过体外腹侧中脑内的局部作用深刻调节多巴胺能中脑神经元的活动，并且与体内情况类似，在VTA中引发更强的效应。
