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

2000; Elsevier BV; Volume: 99; Issue: 3 Linguagem: Inglês

10.1016/s0925-4927(00)00076-7

1872-7506

Pilar Rosel, Belén Arranz, Luis San, Julio Vallejo, José Manuel Crespo, Mikel Urretavizcaya, Miguel Navarro,

Ion channel regulation and function

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.