Variations in [3H]imipramine and 5-HT2A but not [3H]paroxetine binding sites in suicide brains.
Both the [3H]imipramine and [3H]paroxetine binding sites and the 5-HT2A 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 (Bmax) 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 (Kd). Furthermore, a significant decrease in the number of 5-HT2A binding sites, together with a significantly lower Kd, 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 Bmax or Kd 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-HT2A 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-HT2A 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-HT2A receptors are reliable markers of serotonergic dysfunction.
Rosel
P
P
Department of Clinical Chemistry, Hospital Princeps D'Espanya, Barcelona, Spain.
Arranz
B
B
Vallejo
J
J
Oros
M
M
Crespo
J M
JM
Menchon
J M
JM
Navarro
M A
MA
D000328:Adult; D000368:Aged; D000679:Amygdala / Q000737:chemistry; D000929:Antidepressive Agents, Tricyclic / Q000378:metabolism*; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000032:analysis*; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry; D006179:Gyrus Cinguli / Q000737:chemistry; D006624:Hippocampus / Q000737:chemistry; D006801:Humans; D007099:Imipramine / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000378:metabolism*; D011955:Receptors, Drug / Q000032:analysis*; D011985:Receptors, Serotonin / Q000032:analysis; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism*; D013405:Suicide
D000929:Antidepressive Agents, Tricyclic; D002352:Carrier Proteins; D007099:Imipramine; D017374:Paroxetine; D011955:Receptors, Drug; D011985:Receptors, Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C027775:imipramine receptor; C092604:paroxetine receptor