Pharmacological effects of serotonin reuptake inhibitors.

The effects of a series of tricyclic and non-tricyclic antidepressants on the transport of [3H]-serotonin into synaptosomal fractions from rat brain in vitro and in vivo are summarized. Differences in potency in vitro and in vivo would appear to be due partly to the presence of active metabolites, formed in vivo, that show different selectivities for the serotonin transport site. Evidence suggests that the initial reduction in serotonin turnover after acute administration of serotonin reuptake inhibitors is followed by a return to control values after the drug has been administered for at least 2 weeks. These changes in amine turnover are associated with normalization of both the serotonergic and beta-adrenergic receptor systems. Evidence suggests that changes in neurotransmitter receptor numbers and function of blood cells (platelets and lymphocytes) in depressed patients are possible state markers of the illness and that antidepressant efficacy may not be directly associated with specificity of amine reuptake inhibition. Studies also show that the bilaterally bulbectomized rat exhibits deficits in platelet and synaptosomal serotonin transport that resemble those shown in depressed patients. This animal model of depression may be useful not only for detecting putative antidepressants but also for studying the mode of action of such drugs during chronic administration.