title: P-chlorophenylalanine increases glutamate receptor 1 transcription in rat amygdala.
abstract: The amygdala is a key limbic structure strongly implicated in both epilepsy and anxiety disorders. Epilepsy-like mechanisms involve an increased glutamatergic activity, whereas disturbances in serotonin [5-hydroxytryptamine (5-HT)] systems are associated with anxiety-like behavior. Previous studies suggest that low 5-HT increases amygdala excitability, but the molecular mechanisms are not well characterized. Herein we explore the ability of low serotonin to increase glutamate receptor transcription. Using quantitative reverse transcriptase-polymerase chain reaction, we found that rats treated with P-chlorophenylalanine, an inhibitor of tyrosine-5-hydroxylase, resulted in a 21-fold increase in glutamate receptor 1 (GluR1) mRNA expression in the amygdala. These results suggest that low 5-HT induces hyperexcitability of amygdala neurons by increasing GluR1 transcription, and the upregulation of amygdala GluR1 may be important in the pathophysiology of anxiety disorders.
authors.affiliation: Institute for Biomedical Studies, Baylor University, Waco, Texas, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Tran
authors.forename: N Bradley
authors.initials: NB
authors.lastname: Keele
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000378:metabolism; D010134:Fenclonine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D010134:Fenclonine; D012333:RNA, Messenger; D018091:Receptors, AMPA; D012702:Serotonin Antagonists