Serotonin depletion produces long lasting increase in striatal glutamatergic transmission

The ability of serotonin (5-HT) to influence striatal glutamatergic transmi ssion was examined by determining changes over time in glutamate extracellu lar levels, transporter expression and synaptosomal uptake in rats with les ion of serotonergic neurones. By 8 days after intraraphe injections of 5,7- dihydroxytryptamine, producing 80% decreases in striatal tissue 5-HT levels , no changes were observed in the glutamatergic transmission. When 5-HT dep letion was almost complete (21 days post-lesion), high affinity glutamate u ptake in striatal synaptosomal preparations was significantly increased (15 6% of control), although no changes in striatal GLT1, GLAST and EAAC1 mRNAs , and GLT1 protein were detected by in situ hybridization and immunohistoch emistry. Meanwhile, the serotonin lesion produced large increases in basal extracellular levels of glutamate and glutamine (364% and 259%, respectivel y) determined in awake rats by in vivo microdialysis, whereas no change was observed in dopamine levels as compared with control rats. High potassium depolarization as well as L-trans-pyrrolidine-2,4-dicarboxylate, also induc ed larger increases in extracellular levels of glutamate in lesioned rats t han in controls. Finally, similar changes in glutamate transmission were ob served by 3 months post-lesion. These results suggest that 5-HT has a long lasting and tonic inhibitory influence on the striatal glutamatergic input, without affecting the basal dopaminergic transmission.