Long term depletion of serotonin leads to selective changes in glutamate receptor subunits.
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)-[(3)H]alpha-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 [(3)H]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.
Shutoh
F
F
Neurobiology Laboratory, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Hamada
S
S
Shibata
M
M
Narita
M
M
Shiga
T
T
Azmitia
E C
EC
Okado
N
N
D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D010134:Fenclonine / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000172:deficiency*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D012701:Serotonin; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D010134:Fenclonine; D009638:Norepinephrine