[3H]paroxetine binding in rat frontal cortex strongly correlates with [3H]5-HT uptake: effect of administration of various antidepressant treatments

Neuropharmacology. 1993 Aug;32(8):737-43. doi: 10.1016/0028-3908(93)90181-2.


Paroxetine is a selective and potent inhibitor of 5-hydroxytryptamine (5-HT) uptake into serotonergic neurones. [3H]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. [3H]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 [3H]paroxetine binding to rat frontal cortical membranes and [3H]5-HT uptake into rat frontal cortical synaptosomes. These data support the view that [3H]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. [3H]Paroxetine binding parameters (Kd and Bmax) were unaltered by all treatments. It would, therefore, appear that antidepressant therapy does not produce adaptive changes in 5-HT uptake sites.

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Binding, Competitive / drug effects
  • Electroshock
  • In Vitro Techniques
  • Kinetics
  • Male
  • Membranes / drug effects
  • Membranes / metabolism
  • Paroxetine / metabolism*
  • Prefrontal Cortex / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism*
  • Serotonin Uptake Inhibitors / pharmacology*
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism


  • Antidepressive Agents
  • Serotonin Uptake Inhibitors
  • Serotonin
  • Paroxetine