Aston-Jones G, Akaoka H, Charléty P, Chouvet G
INSERM Unité 171 and CNRS URA1195, Centre Hospitalier Lyon Sud, Pierre Bénite, France.
J Neurosci. 1991 Mar;11(3):760-9. doi: 10.1523/JNEUROSCI.11-03-00760.1991.
The effect of 5-HT on activity of noradrenergic locus coeruleus (LC) neurons was studied using microiontophoretic and micropressure drug application in anesthetized rats. 5-HT had no consistent effect on LC spontaneous discharge, eliciting a modest decrease overall. However, 5-HT reliably attenuated responses of LC neurons to excitatory amino acids (EAAs), one of the major classes of transmitters in afferents to these neurons. This effect was specific for EAA responses because it occurred for glutamate and kainate but not for ACh. In contrast, iontophoretic norepinephrine (NE) selectively attenuated spontaneous activity but not responses evoked by either glutamate or ACh. The responsiveness of LC neurons to EAAs as quantified by a response-contrast measure (evoked excitation/basal activity) was markedly reduced by 5-HT, but was increased by NE. For ACh, such responsiveness of LC cells was not changed by 5-HT, but was increased by NE. The effects of 5-HT were prevented and reversed by iontophoretically applied antagonists of 5-HT receptors, methysergide and methiothepin. Thus, 5-HT appears to selectively interact with EAA responses of LC neurons, acting as a filter to attenuate LC activity linked to its major EAA inputs while allowing other channels afferent to the LC (e.g., those utilizing ACh) to be expressed.
采用微量离子电泳和微量压力给药技术，在麻醉大鼠中研究了5-羟色胺对去甲肾上腺素能蓝斑（LC）神经元活动的影响。5-羟色胺对LC自发放电没有一致的影响，总体上引起适度下降。然而，5-羟色胺可靠地减弱了LC神经元对兴奋性氨基酸（EAA）的反应，EAA是这些神经元传入纤维中的主要递质类别之一。这种作用对EAA反应具有特异性，因为它对谷氨酸和海人酸发生作用，但对乙酰胆碱不发生作用。相反，离子电泳去甲肾上腺素（NE）选择性地减弱自发放电，但不减弱由谷氨酸或乙酰胆碱诱发的反应。通过反应对比测量（诱发兴奋/基础活动）量化的LC神经元对EAA的反应性，5-羟色胺使其显著降低，但NE使其增加。对于乙酰胆碱，5-羟色胺不改变LC细胞的这种反应性，但NE使其增加。离子电泳应用5-羟色胺受体拮抗剂麦角新碱和甲硫哒嗪可阻止并逆转5-羟色胺的作用。因此，5-羟色胺似乎选择性地与LC神经元的EAA反应相互作用，充当一种过滤器，减弱与其主要EAA输入相关的LC活动，同时允许传入LC的其他通道（例如，那些利用乙酰胆碱的通道）得以表达。
