Li X, Rainnie D G, McCarley R W, Greene R W
Harvard Medical School and Brockton Veterans Administration Medical Center, Neuroscience Laboratory, Brockton, Massachusetts 02401, USA.
J Neurosci. 1998 Mar 1;18(5):1904-12. doi: 10.1523/JNEUROSCI.18-05-01904.1998.
Nicotine is reported to increase arousal and attention and to elevate mood, effects that are most often associated with changes in the function of monoaminergic neuromodulatory systems (Feldman et al., 1997). Recent studies have shown a nicotinic receptor-mediated presynaptic enhancement of fast glutamatergic (McGehee et al., 1995; Gray et al., 1996) and GABAergic (Lena and Changeux, 1997) transmission. However, the mechanism of nicotinic effects on metabotropic-mediated transmission in general, and on monoaminergic transmission in particular, is less well understood. We have examined nicotinic effects on dorsal raphe neurons of rats using whole-cell current and voltage-clamp recording techniques in vitro. In the majority of these neurons, activation of presynaptic nicotinic receptors induced a depolarization mediated by norepinephrine acting on alpha1 receptors. Blockade of this response revealed a hyperpolarization mediated by serotonin acting on 5-HT1A receptors. Because the norepinephrine effect was sensitive to methyllycaconitine (100 nM), it is concluded that nicotinic receptors with an alpha7 subunit can facilitate release of norepinephrine to activate metabotropic receptors. In contrast, methyllycaconitine-insensitive nicotinic receptors can induce 5-HT release in the dorsal raphe nucleus.
据报道，尼古丁可提高觉醒和注意力，并改善情绪，这些作用通常与单胺能神经调节系统功能的变化有关（费尔德曼等人，1997年）。最近的研究表明，烟碱型受体介导快速谷氨酸能（麦克吉等人，1995年；格雷等人，1996年）和GABA能（莱娜和尚热，1997年）传递的突触前增强。然而，烟碱对一般代谢型介导传递，特别是对单胺能传递的作用机制，人们了解较少。我们利用体外全细胞电流和电压钳记录技术，研究了烟碱对大鼠中缝背核神经元的影响。在这些神经元中的大多数，突触前烟碱型受体的激活诱导了由去甲肾上腺素作用于α1受体介导的去极化。对这种反应的阻断揭示了由5-羟色胺作用于5-HT1A受体介导的超极化。由于去甲肾上腺素的作用对甲基lycaconitine（100 nM）敏感，因此得出结论，具有α7亚基的烟碱型受体可促进去甲肾上腺素的释放，以激活代谢型受体。相比之下，对甲基lycaconitine不敏感的烟碱型受体可诱导中缝背核中5-羟色胺的释放。
