LOWER H-3 PAROXETINE BINDING IN CEREBRAL-CORTEX OF SUICIDE VICTIMS ISPARTLY DUE TO FEWER HIGH-AFFINITY, NON-TRANSPORTER SITES

Suicide has been associated with decreased serotonin transmission. Mea surement of concentrations of serotonin, its precursors tryptophan (TR Y) and 5-hydroxytryptophan (5-HTP) and its metabolite 5-hydroxyindolea cetic acid (5-HIAA), have been used as indices of serotonin activity, and with serotonin transporter binding, are indices of the integrity o f serotonin nerve terminals. Most previous studies have not distinguis hed high affinity transporter binding from a very similar nontransport er binding site, where binding is not dependent on Na+ or Cl- and that does not have a known functional role. We therefore, assayed binding kinetics in prefrontal (PFC) and temporal cortex (TC) in matched pairs of suicide victims and controls using the selective ligand H-3-paroxe tine, and employing 1 mu M sertraline to define specific binding to th e transporter and 10 mu M sertraline which also displaces binding to t he high affinity, nontransporter site. In addition, we measured concen trations of TRY, 5-HTP, serotonin and 5-HIAA in the same brain areas. The total number of H-3-paroxetine transporter and nontransporter bind ing sites (B-max), was lower in the suicide group compared to controls in both Brodmann area 9 (prefrontal cortex; p = 0.02) and in Brodmann area 38 (temporal cortex, p = 0.01). In contrast, no differences were found in the number of high affinity transporter binding sites and co ncentrations of serotonin, 5-HIAA, 5-HTP or TRY (p > 0.05). We conclud e that the number of serotonin transporter sites is not altered in Bro dmann area 9 in suicide, and that fewer H-3-paroxetine and 3H-imiprami ne binding sites found in this region of cerebral cortex of suicides m ay be explained by a reduction in the nontransporter binding sites.