Serotonin _1A receptor ligands act on norepinephrine neuron firing through excitatory amino acid and GABA_A receptors: A microiontophoretic study in the rat locus coeruleus

• Steven T. Szabo

• Pierre Blier

抄録

It was previously shown that the excitatory effect of the 5‐HT 1A agonist 8‐OH‐DPAT on firing activity of locus coeruleus (LC) norepinephrine (NE) neurons and the inhibitory action of the 5‐HT 1A antagonist WAY 100,635 are dependent on the presence of 5‐HT neurons, whereas the inhibitory action of the 5‐HT 2 agonist DOI is not. Using in vivo extracellular unitary recordings performed in anesthetized rats, iontophoretic applications of the excitatory amino acid antagonist kynurenate attenuated the enhancement in firing produced by glutamate and kainate. In contrast, GABA applications decreased the firing activity of NE neurons which was attenuated by the enhancement produced by glutamate and kainate. In contrast, GABA applications decreased the firing activity of NE neurons which was attenuated by the GABA A receptor antagonist bicuculline. 8‐OH‐DPAT (10–60 μg kg −1 , i.v.) produced a dose‐dependent enhancement in the firing activity of NE neurons that was abolished in the presence of kynurenate application. The selective 5‐HT 1A receptor antagonist WAY 100,635 (100 μg kg −1 , i.v.) suppressed NE firing which was reversed by the selective 5‐HT 2A antagonist MDL 100,907 (200 μg kg −1 , i.v.). In the presence of bicuculline, the inhibitory effect of WAY 100,635 was blunted. These results suggest that WAY 100,635 mainly attenuates NE neuron firing by blocking inhibitory 5‐HT 1A receptors on glutamatergic neurons, thereby enhancing glutamate release and activating excitatory amino acid receptors, possibly of the kainate subtype, on 5‐HT terminals. The ensuing increased 5‐HT release would then act on excitatory 5‐HT 2A receptors on GABA neurons that would ultimately mediate the inhibition of NE neurons. The prevention of the excitatory action of 8‐OH‐DPAT on NE neuron firing by kynurenate is also consistent with this neurocircuitry. Synapse 42:203–212, 2001. © 2001 Wiley‐Liss, Inc.

収録刊行物

• Synapse

  Synapse 42 (4), 203-212, 2001-10-12

  Wiley

キーワード

• Cellular and Molecular Neuroscience

詳細情報

• CRID: 1360011144119344256
• NII論文ID: 30008332240
• DOI: 10.1002/syn.10009
• ISSN: 10982396
• ISSN: 08874476
• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fsyn.10009
• Web Site: https://onlinelibrary.wiley.com/doi/pdf/10.1002/syn.10009
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