Clinical and experimental studies on fluoxetine: effects on serotonin uptake.
A decreased rate of uptake of serotonin (5HT) into platelets is recognized as a possible marker of the depressed state, being normalized only by effective antidepressant treatment. Fluoxetine is a novel antidepressant, with 5HT uptake inhibitory properties. In this study, treatment of depressed patients with fluoxetine for up to 6 months did not normalize the decreased platelet 5HT uptake rates associated with depression, although the patients showed a clinical recovery. The olfactory bulbectomized (OB) rat shows a characteristic hyperactivity in a stressful environment, which can be reversed only by chronic treatment with most antidepressants. OB rats have been found to exhibit a decreased rate of platelet 5HT uptake, similar to depressed patients, which is normalized by chronic antidepressant treatment. However, 3 weeks treatment with fluoxetine failed to reverse the hyperactivity of the OB rat and the decreased rates of uptake of 5HT. We also examined the rate of uptake of serotonin into the synaptosomes of the OB rats, in order to elucidate whether platelet 5HT uptake reflected central activity. Chronic fluoxetine treatment failed to normalize high affinity synaptosomal 5HT uptake in the OB rat. Fluoxetine, therefore, unlike most other antidepressants, does not normalize the decreased rates of platelet 5HT uptake in depressed patients on clinical recovery. OB rats also showed a deficit in their platelet and synaptosomal 5HT uptake rates, following 3 weeks treatment with fluoxetine.
Butler
J
J
Department of Pharmacology, University College, Galway, Ireland.
Leonard
B E
BE
D000328:Adult; D000368:Aged; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism; D003866:Depressive Disorder / Q000097:blood*; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects
D005473:Fluoxetine; D012701:Serotonin