PLATELET H-3 PAROXETINE BINDING TO THE SEROTONIN TRANSPORTER IS INSENSITIVE TO CHANGES IN CENTRAL SEROTONERGIC INNERVATION IN THE RAT

The serotonin transporter labeled in platelets by H-3-imipramine or H-3-paroxetine binding has been suggested to be a peripheral marker for changes in serotonin uptake in the brain that may be related to depression. The present study was designed to determine whether major changes in central serotonergic innervation modify the platelet serotonin transporter as labeled by H-3-paroxetine binding. Fifteen days after the intracerebroventricular administration of 5,7-dihydroxytryptamine (250-mu-g/animal) to rats to lesion central serotonergic neurons, serotonergic innervation was reduced by 82% in the cortex and 98% in the hippocampus as determined by endogenous serotonin levels. The maximum binding of H-3-paroxetine was reduced by 55% in the cortex and was undetectable in the hippocampus. Serotonin levels and H-3-paroxetine binding in platelets were not, however, significantly modified in the same animals. Thus, following a major serotonergic lesion in the brain, changes in the platelet serotonin transporter do not parallel serotonergic changes in the brain. The hypothesis that binding to the platelet serotonin transporter is a state-dependent marker of brain serotonergic activity therefore appears to be unlikely.