title: Fluoxetine treatment induces EAAT2 expression in rat brain.
abstract: Synaptic pathology and disturbed glutamatergic neurotransmission contribute to the neurobiology of depression. Reduced expression of glutamate transporters, most importantly excitatory amino acid transporter (EAAT2), was reported in human studies and animal models. We therefore assessed the effects of antidepressant treatment upon EAAT2 expression. Male Sprague-Dawley rats received daily intraperitoneal injections of the antidepressants desipramine (DES, N = 7), fluoxetine (FLU, N = 7), tranylcypromine (TRAN, N = 5) or a saline control (CON, N = 5) for a period of 14 days. The expression of the major glial glutamate transporter EAAT2 was evaluated by semi-quantitative in situ hybridizations using a (35)S-labeled cRNA probe. Treatment with FLU significantly induced EAAT2 expression in hippocampal and cortical regions in comparison with saline injections, while DES and TRAN-applications did not exert significant effects. It can be postulated that increased expression of EAAT2 may counterbalance the tonus of glutamatergic neurotransmission. Our findings are in concert with human post-mortem findings, valid animal models of depression, antidepressive effects of NMDA-antagonists, and the glutamatergic theory of depression. Further studies should examine the effects of antidepressant treatments upon EAAT2 expression in rodent models of depression to further elucidate the underlying molecular mechanisms.
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, P.O. Box 122120, 68072 Mannheim, Germany. mathias.zink@zi-mannheim.de
authors.forename: M
authors.initials: M
authors.lastname: Zink
authors.forename: S
authors.initials: S
authors.lastname: Rapp
authors.forename: R
authors.initials: R
authors.lastname: Donev
authors.forename: P J
authors.initials: PJ
authors.lastname: Gebicke-Haerter
authors.forename: J
authors.initials: J
authors.lastname: Thome
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis* / Q000235:genetics; D005473:Fluoxetine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D005473:Fluoxetine; D018698:Glutamic Acid