Variations in [ 3H]imipramine and 5-HT 2A but not [ 3H]paroxetine binding sites in suicide brains

Abstract

Both the [ 3H]imipramine and [ 3H]paroxetine binding sites and the 5-HT 2A receptor were simultaneously determined in frontal cortex, cingulate cortex, hippocampus and amygdala from 17 control subjects and 17 depressed suicide victims. A significant decrease in the maximum binding ( B max) of [ 3H]imipramine was observed in the hippocampus of suicide victims as compared to control subjects (160±25 vs. 328±52 fmol/mg protein; P=0.007) without changes in the apparent affinity constant ( K d). Furthermore, a significant decrease in the number of 5-HT 2A binding sites, together with a significantly lower K d, was also observed in the hippocampus of suicides as compared to control subjects (129±18 vs. 225±32 fmol/mg protein; P=0.02 and 0.91±0.07 vs. 1.38±0.08 nM, respectively; P=0.006). [ 3H]Paroxetine binding did not display modifications between the two groups in either B max or K d from any of the brain regions studied. When all four brain regions were taken together, a down-regulation was noted between presynaptic [ 3H]imipramine binding and the postsynaptic 5-HT 2A receptor ( r=−0.40; P=0.0013) in the control group. This correlation did not appear in the suicide group. No correlation was observed between [ 3H]paroxetine binding and the 5-HT 2A receptor in either control subjects or suicides. Taken together, these results suggest that the 5-HT uptake site measured with [ 3H]imipramine and the 5-HT 2A receptors are reliable markers of serotonergic dysfunction.