[H-3] PAROXETINE BINDING IN RAT FRONTAL-CORTEX STRONGLY CORRELATES WITH [H-3] 5-HT UPTAKE - EFFECT OF ADMINISTRATION OF VARIOUS ANTIDEPRESSANT TREATMENTS

Paroxetine is a selective and potent inhibitor of 5-hydroxytryptamine (5-HT) uptake into serotonergic neurones. [H-3]Paroxetine binding to rat frontal cortex was of high affinity with a high percentage of specific binding. The binding data of both competition and saturation studies fitted a single site binding model. [H-3]Paroxetine binding was potently inhibited by the selective 5-HT uptake inhibitors. In addition, a very good correlation was demonstrated between the ability of twenty-three compounds to inhibit [H-3]paroxetine binding to rat frontal cortical membranes and [H-3]5-HT uptake into rat frontal cortical synaptosomes. These data support the view that [H-3]paroxetine binds to a single site which corresponds to the 5-HT uptake site. Using this ligand, the effects of repeated administration of antidepressant drugs with a wide range of pharmacological actions and electroconvulsive shock on 5-HT reuptake sites were examined. [H-3]Paroxetine binding parameters (K(d) and B(max)) were unaltered by all treatments. It would, therefore, appear that antidepressant therapy does not produce adaptive changes in 5-HT uptake sites.