p-Chlorophenylalanine (PCPA) Increases GluR1 Transcription in Rat Amygdala

The amygdala is a key limbic structure strongly implicated in both epilepsy and anxiety disorders. Epilepsy-like mechanisms involve increased glutamatergic activity, whereas disturbances in serotonin (5-HT) systems are associated with anxiety-like behavior. Previous studies suggest low 5-HT increases amygdala excitability, but the molecular mechanisms are not well-characterized. Here we explore the ability of low serotonin to increase glutamate receptor transcription. Using quantitative RT-PCR, 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 LA neurons by increasing GluR1 transcription, and the upregulation of amygdala GluR1 may be important in the pathophysiology of anxiety disorders.