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 [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.