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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
Author(s) -
Szabo Steven T.,
Blier Pierre
Publication year - 2001
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10009
Subject(s) - kainate receptor , bicuculline , excitatory postsynaptic potential , inhibitory postsynaptic potential , kainic acid , glutamate receptor , chemistry , agonist , glutamatergic , locus coeruleus , pharmacology , neuron , antagonist , receptor antagonist , ampa receptor , receptor , neuroscience , biology , biochemistry , central nervous system
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.