PLATELET 5-HYDROXYTRYPTAMINE (5-HT) TRANSPORTER AND 5-HT2A RECEPTOR-BINDING AFTER CHRONIC HYPERCORTICOSTERONEMIA, (+ -)-1-(2,5-DIMETHOXY-4-IODOPHENYL)-2-AMINOPROPANE ADMINISTRATION OR NEUROTOXIN-INDUCED DEPLETION OF CENTRAL-NERVOUS-SYSTEM 5-HT IN THE RAT/

There is considerable evidence that the number of platelet 5-hydroxytr yptamine (5-HT) transporter binding sites, as measured by [H-3]imipram ine binding, are significantly decreased, and platelet 5-HT2 receptor density is increased, in drug-free patients with major depression. To investigate whether these changes in the platelet 5-HT transporter or 5-HT2 receptor sites resulted from known or hypothesized biochemical c hanges observed in major depression, we examined, in the rat, whether a chronic hyperglucocorticoid state, or decreases or increases in cent ral nervous system 5-HT neurotransmission, altered binding of the sele ctive ligands [H-3]citalopram and [I-125](+/-)-1- (2,5-dimethoxy-4-iod opheny1)-2-aminoprapane to platelet and brain 5-HT transporters and 5- HT2 receptors, respectively. Chronic (6 weeks) hypercorlicosteronemia did not alter either brain or platelet 5-HT transporter or 5-HT2A rece ptor binding. Similarly, 8-week administration of the 5-HT2A/5-HT2C ag onist +/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane at a dose; wh ich down-regulates brain 5-HT2A/2C receptors, did not alter brain or p latelet 5-HT transporters or platelet 5-HT2A receptors. Additionally, para-chloroamphetamine- (11 weeks) or fenfluramine-induced chronic (1. 5-10 weeks) depletion of central newous system 5-HT did not alter plat elet 5-HT transporter or 5-HT2A receptor binding. Finally, there was n o correlation between the number of 5-HT transporters in brain and pla telets in any of the control or treatment groups. These findings sugge st that the observed changes in platelet 5-HT transporter and 5-HT2A r eceptor binding in depressed patients are more apt to be of genetic or igin (i.e., trait-dependent) rather than an epiphenomenon of hypercort isolemia or altered central nervous system 5-HT status.