Altered 5-HT2A binding sites and second messenger inositol trisphosphate (IP3) levels in hippocampus but not in frontal cortex from depressed suicide victims

The binding parameters of 5-HT2A and levels of its second messenger, 1,4,5-trisphosphate (IP3), were simultaneously studied in frontal cortex and hippocampus from the brains of 18 control subjects and 18 depressed suicide victims. All suicides met DSM-III-R criteria for depressive symptoms, suffered a violent death and had not taken any antidepressant drugs for at least 6 months prior to death. A significant decrease in the number of 5-HT2A binding sites (154 +/- 22 vs. 254 +/- 36 fmol/mg), together with a significantly lower apparent affinity constant (1.02 +/- 0.08 vs. 1.36 +/- 0.09 nM), was detected in hippocampus but not in frontal cortex from the depressed suicides compared to the control subjects. Furthermore, IP3 concentrations were significantly increased in hippocampus (3.2 +/- 0.3 vs. 2.1 +/- 0.3 pmol/g) but not in frontal cortex (1.3 +/- 0.3 vs. 2.7 +/- 0.5 pmol/g) from the suicide victims. The reported results may indicate a significant hypersensitivity of the 5-HT2A postsynaptic receptor located in the hippocampus from depressed suicide victims, giving rise to an enhancement of its intracellular signaling system with higher IP3 production. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.