title: Evaluation of 5-HT2A and mGlu2/3 receptors in postmortem prefrontal cortex of subjects with major depressive disorder: effect of antidepressant treatment.
abstract: Several studies have demonstrated alterations in serotonin 5-HT2A (5-HT2AR) and glutamate metabotropic mGlu2 (mGlu2R) receptors in depression, but never in the same sample population. Recently it has been shown that both receptors form a functional receptor heterocomplex that is altered in schizophrenia. The present study evaluates the gene expression and protein density of 5-HT2AR and mGlu2/3R in the postmortem prefrontal cortex of subjects with major depressive disorder (n = 14) compared with control subjects (n = 14) in a paired design. No significant differences between subjects with depression and controls in the relative mRNA levels of the genes HTR2A, GRM2 and GRM3 were observed. The 5-HT2AR density evaluated by [(3)H]ketanserin binding was significantly lower in antidepressant-treated subjects (Bmax = 313 ± 17 fmol/mg protein; p < 0.05) compared to controls (Bmax = 360 ± 12 fmol/mg protein) but not in antidepressant-free subjects (Bmax = 394 ± 16 fmol/mg protein; p > 0.05). In rats, chronic treatment with citalopram (10 mg/kg/day) and mirtazapine (5 mg/kg/day) decreased mRNA expression and 5-HT2AR density whereas reboxetine (20 mg/kg/day) modified only mRNA expression. The mGlu2/3R density evaluated by [(3)H]LY341495 binding was not significantly different between depression and control subjects. The present results demonstrate no changes in expression and density of both 5-HT2AR and mGlu2/3R in the postmortem prefrontal cortex of subjects with major depressive disorder under basal conditions. However, antidepressant treatment induces a decrease in 5-HT2AR density. This finding suggests that 5-HT2AR down-regulation may be a mechanism for antidepressant effect.
authors.affiliation: Department of Pharmacology, University of the Basque Country UPV/EHU, and Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Muguruza
authors.affiliation: Department of Pharmacology, University of the Basque Country UPV/EHU, and Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Miranda-Azpiazu
authors.affiliation: Department of Pharmacology, University of the Basque Country UPV/EHU, and Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Díez-Alarcia
authors.affiliation: Section of Forensic Pathology, Basque Institute of Legal Medicine, Bilbao, Spain.
authors.forename: Benito
authors.initials: B
authors.lastname: Morentin
authors.affiliation: Departments of Psychiatry, Neurology, and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: González-Maeso
authors.affiliation: Department of Pharmacology, University of the Basque Country UPV/EHU, and Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain; Biocruces Health Research Institute, Bizkaia, Spain. Electronic address: lf.callado@ehu.es.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Callado
authors.affiliation: Department of Pharmacology, University of the Basque Country UPV/EHU, and Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain; Biocruces Health Research Institute, Bizkaia, Spain.
authors.forename: J Javier
authors.initials: JJ
authors.lastname: Meana
mesh_terms: D000596:Amino Acids; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015283:Citalopram / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007650:Ketanserin; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D009025:Morpholines / Q000627:therapeutic use; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011869:Radioligand Assay; D017207:Rats, Sprague-Dawley; D000077593:Reboxetine; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D014316:Tritium; D014966:Xanthenes
chemical_list: D000596:Amino Acids; D000928:Antidepressive Agents; C114624:LY 341495; D009025:Morpholines; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D015283:Citalopram; D014316:Tritium; D008803:Mianserin; D000077593:Reboxetine; D007650:Ketanserin; D000078785:Mirtazapine
keywords: 5-HT(2A) receptors; Antidepressants; Depression; Human brain; mGlu(2/3) receptors