Abstract
Serotonin (1-40 microM) reduced input resistance by 20.6 +/- 6% and hyperpolarized stellate and pyramidal neurons of layers two and three of the lateral entorhinal cortex. 5-Carboxamidotryptamine, a 5-HT1 agonist, and the selective 5-HT1A agonist 8-hydroxy-dipropylaminotetralin mimicked the action of serotonin. The reversal potential of 5-HT-mediated hyperpolarizations was sensitive to the extracellular K+ concentration, indicating a potassium conductance change. Serotonin treatment suppressed excitatory amino acid-mediated synaptic potentials (by 48%, Kd = 6.9 microM) and responses to exogenously applied glutamate (70.1 +/- 17% of control, n = 7), but did not alter paired-pulse facilitation, indicating a postsynaptic site of action. Intracellular application of QX-314, a blocker of potassium conductance, significantly reduced depression of synaptic potentials by 5-HT agonists. In cells filled with QX-314, responses to exogenously applied glutamate were not reduced by serotonin or 5-carboxamidotryptamine application. These results indicate that the observed conductance increase associated with 5-HT application accounts for most if not all of the observed depressant effects of 5-HT1A agonists on excitatory amino acid-mediated neurotransmission.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2-Amino-5-phosphonovalerate / pharmacology
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6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
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8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
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Anesthetics, Local / pharmacology
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Animals
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Electrophysiology
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Entorhinal Cortex / cytology*
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Entorhinal Cortex / drug effects
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Glutamic Acid / pharmacology
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Lidocaine / analogs & derivatives
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Lidocaine / pharmacology
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Lysine / analogs & derivatives
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Male
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Neural Inhibition / drug effects*
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Neurons / chemistry
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Neurons / drug effects
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Neurons / physiology
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Perforant Pathway / drug effects
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Potassium / pharmacology
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Potassium Channels / agonists
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Potassium Channels / metabolism*
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Propranolol / pharmacology
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Rats
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Rats, Wistar
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, Serotonin / metabolism*
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Receptors, Serotonin, 5-HT1
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Serotonin / analogs & derivatives
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Serotonin / pharmacology*
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Serotonin Receptor Agonists / pharmacology
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Sympatholytics / pharmacology
Substances
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Anesthetics, Local
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Excitatory Amino Acid Antagonists
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Potassium Channels
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Receptors, N-Methyl-D-Aspartate
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Receptors, Serotonin
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Receptors, Serotonin, 5-HT1
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Serotonin Receptor Agonists
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Sympatholytics
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QX-314
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Serotonin
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Glutamic Acid
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6-Cyano-7-nitroquinoxaline-2,3-dione
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2-Amino-5-phosphonovalerate
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8-Hydroxy-2-(di-n-propylamino)tetralin
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5-carboxamidotryptamine
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Lidocaine
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Propranolol
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biocytin
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Lysine
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Potassium