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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: 5-Hydroxytryptophan, Animals, Antidepressive Agents, Cell Division, Desipramine, Dopamine Uptake Inhibitors, Fenclonine, Fluoxetine, Lymphocyte Activation, Lymphocytes, Male, Mitogens, Neurons, Piperazines, Rats, Rats, Sprague-Dawley, Serotonin, Serotonin Antagonists, Serotonin Uptake Inhibitors, Sertraline, p-Chloroamphetamine.
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Do specific serotonin reuptake inhibitor-induced decreases in lymphocyte activity require endogenous serotonin release? Context: We have previously reported that acute administration of the specific serotonin reuptake inhibitor (SSRI), fluoxetine, resulted in a decrease in mitogen-induced blood lymphocyte proliferation. The present studies further examine the specificity of this response to serotonin reuptake systems and the potential role of endogenous serotonin in mediating these effects. Male Sprague-Dawley rats were treated intraperitoneally with the SSRIs, fluoxetine (6-10 mg/kg) or sertraline (20 mg/kg), dopamine and norepinephrine reuptake inhibitors, GBR 12909 and desipramine, respectively (6 mg/kg) or the serotonin precursor, 5-hydoxytryptophan (5-HTP, 50 mg/kg) 2 h prior to sacrifice. The serotonin-depleting agents, p-chlorophenylalanine (PCPA, 2 x 200 mg/kg) or the serotonin-lesioning agent, p-chloroamphetamine (PCA, 2 x 10 mg/kg) were administered intraperitoneally 5-7 days prior to fluoxetine (10 mg/kg) administration. Unlike the SSRIs, which significantly suppressed lymphocyte proliferation responses, selective norepinephrine or dopamine reuptake inhibition had no effect on lymphocyte proliferation. Elevation of extracellular serotonin levels with the serotonin precursor, 5-HTP, resulted in a similar decrease in lymphocyte proliferation as that seen with SSRI administration. Conversely, decreases in endogenous serotonin following PCA or PCPA treatment prevented the fluoxetine-induced decreases in lymphocyte proliferation.
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These results suggest that decreases in mitogen-induced lymphocyte proliferation following acute fluoxetine administration were due to elevations in extracellular serotonin following reuptake inhibition. Final Decision: yes