Evaluation of 5-HT2A and mGlu2/3 receptors in postmortem prefrontal cortex of subjects with major depressive disorder: Effect of antidepressant treatment

• Published in: Neuropharmacology 2014-11, Vol.86, p.311-318
• Main Authors: Muguruza, Carolina, Miranda-Azpiazu, Patricia, Díez-Alarcia, Rebeca, Morentin, Benito, González-Maeso, Javier, Callado, Luis F., Meana, J. Javier
• Format: Article
• Language: English
• Subjects: 5-HT2A receptors; Amino Acids; Animals; Antidepressants; Antidepressive Agents - therapeutic use; Citalopram - therapeutic use; Depression; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - metabolism; Down-Regulation; Female; Human brain; Humans; Ketanserin; Male; mGlu2/3 receptors; Mianserin - analogs & derivatives; Mianserin - therapeutic use; Middle Aged; Mirtazapine; Morpholines - therapeutic use; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Radioligand Assay; Rats, Sprague-Dawley; Reboxetine; Receptor, Serotonin, 5-HT2A - metabolism; Receptors, Metabotropic Glutamate - metabolism; RNA, Messenger - metabolism; Tritium; Xanthenes
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2014.08.009

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 [3H]ketanserin binding was significantly lower in antidepressant-treated subjects (Bmax = 313 ± 17 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 [3H]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. •5-HT2AR density was lower in patients with depression under antidepressant treatment.•5-HT2AR down-regulation may be a mechanism for antidepressant effect.•mGlu2/3R expression and density are not altered in subjects with depression.