Long term depletion of serotonin leads to selective changes in glutamate receptor subunits

• Published in: Neuroscience research Vol. 38; no. 4; pp. 365 - 371
• Main Authors: Shutoh, Fumihiro, Hamada, Shun, Shibata, Michiyo, Narita, Masaaki, Shiga, Takashi, Azmitia, Efrain C., Okado, Nobuo
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.12.2000
• Subjects: (S)-[3H]α-amino-3-hydroxy-5-methylisoxazol-4-propionic acid (AMPA); alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacology; Animals; Binding Sites - drug effects; Binding Sites - physiology; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Dizocilpine Maleate - pharmacology; Excitatory amino acid; Fenclonine - pharmacology; Glutamate receptor; Glutamic Acid - metabolism; Male; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Norepinephrine - metabolism; Plasticity; Radioligand Assay; Rats; Rats, Wistar; Receptors, AMPA - chemistry; Receptors, AMPA - drug effects; Receptors, AMPA - metabolism; Receptors, N-Methyl-D-Aspartate - chemistry; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, N-Methyl-D-Aspartate - metabolism; Serotonin - deficiency; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Time Factors; Tritium; (S)-[3H]α-amino-3-hydroxy-5-methylisoxazol-4-propionic acid (AMPA); Excitatory amino acid; Glutamate receptor; Plasticity
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/S0168-0102(00)00184-X

The present study was carried out to clarify possible modulation mechanism of serotonin (5-HT) on glutamatergic neurotransmission in the rat cerebral cortex. 5-HT was depleted by a 5-HT metabolite blocker (para-chlorophenylalanine; pCPA) for a week. Receptor binding experiments using (S)-[ 3H]α-amino-3-hydroxy-5-methylisoxazol-4-propionic acid (AMPA) showed a considerable increase in B max value of the membrane samples prepared from the cerebral cortex of rats compared with that of control animals received saline. In contrast, B max value of the [ 3H]MK-801 binding experiments for NMDA receptor was not changed by pCPA-treatment. Changes in the density of each AMPA receptor subtype were examined in the cerebral cortex by immunoblot analyses using antibodies against AMPA receptor subunits. The density of immunoreactive bands with receptor subtype specific antibodies against GluR2/3 and GluR2 receptors was increased, whereas that of GluR1 receptors was decreased. Considering GluR2 receptor subtype inhibits Ca 2+ influx into neurons, the present study suggests that 5-HT appears to modulate synaptic plasticity by regulating the density of each AMPA receptor subtype.