[H-3] PAROXETINE BINDING AND SEROTONIN CONTENT OF RAT-BRAIN - ABSENCEOF CHANGES FOLLOWING ANTIDEPRESSANT TREATMENTS

The high affinity binding of [H-3]paroxetine was measured in rat cereb ral cortex following chronic treatment (21 days) with imipramine (5 mg /kg), trimipramine (5 mg/kg) and fluoxetine (2 mg/kg),in adult (3-4 mo nths) or neonatal (7 days of age) rats. Tissue concentrations of serot onin and of its metabolite 5-hydroxyindole-3-acetic acid were also det ermined by high-performance liquid chromatography in cingulate cerebra l cortex, rostral neostriatum, hippocampus and midbrain raphe nucleus region. No differences were found in any of the parameters of [H-3]par oxetine binding after antidepressant administration, in either adult o r neonatal animals. In addition, endogenous serotonin and 5-hydroxyind ole-3-acetic acid levels were not different from control values in any of the regions examined. The present study shows that the serotonin u ptake recognition site is resilient to changes after chronic treatment with therapeutic doses of antidepressants, and emphasizes the potenti al usefulness of uptake site ligands as markers to quantify innervatio n densities within the brain.