Serotonin depletion produces long lasting increase in striatal glutamatergic transmission.
The ability of serotonin (5-HT) to influence striatal glutamatergic transmission was examined by determining changes over time in glutamate extracellular levels, transporter expression and synaptosomal uptake in rats with lesion 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 depletion was almost complete (21 days post-lesion), high affinity glutamate uptake in striatal synaptosomal preparations was significantly increased (156% of control), although no changes in striatal GLT1, GLAST and EAAC1 mRNAs, and GLT1 protein were detected by in situ hybridization and immunohistochemistry. Meanwhile, the serotonin lesion produced large increases in basal extracellular levels of glutamate and glutamine (364% and 259%, respectively) 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 induced larger increases in extracellular levels of glutamate in lesioned rats than in controls. Finally, similar changes in glutamate transmission were observed 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.
Di Cara
B
B
Laboratoire de Neurobiologie Cellulaire et Fonctionnelle, CNRS, Marseille, France.
Dusticier
N
N
Forni
C
C
Lievens
J C
JC
Daszuta
A
A
D015116:5,7-Dihydroxytryptamine / Q000008:administration & dosage / Q000494:pharmacology*; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism; D018846:Excitatory Amino Acids / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D017403:In Situ Hybridization; D017551:Microdialysis; D008845:Microinjections; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology*; D014158:Transcription, Genetic
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D018846:Excitatory Amino Acids; D018490:Serotonin Agents; D005973:Glutamine; D001224:Aspartic Acid; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D018698:Glutamic Acid; D006897:Hydroxyindoleacetic Acid; D004298:Dopamine