Effects of single and chronic treatment with tranylcypromine on extracellular serotonin in rat brain.
We have examined the effects of tranylcypromine, a monoamine oxidase inhibitor used as antidepressant, on the tissue and extracellular concentration of serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in frontal cortex and dorsal raphe nucleus using microdialysis in conscious rats. Single treatment with tranylcypromine sulphate (0.5, 3 and 15 mg/kg, i.p.) dose dependently elevated dialysate 5-HT in both areas but more markedly in the DRN. Extracellular and tissue 5-HT concentrations were affected by the drug in a different manner. The former increased sharply when tissue 5-HT reached a plateau. This may have reflected saturation of intracellular stores and overflow of the amine. In contrast, tissue and extracellular 5-HIAA concentrations--that indicate metabolic effects of tranylcypromine--were affected similarly. A 2-week treatment with 0.5 mg/kg.day of tranylcypromine sulphate increased basal extracellular 5-HT in frontal cortex and dorsal raphe nucleus (ca. 220%) whereas a further injection of 0.5 mg/kg was without effect in both areas. Thus, chronic, but not acute, treatment with low doses of tranylcypromine increases extracellular 5-HT concentration, suggesting that clinical effects of this monoamine oxidase inhibitor are related to its capacity to enhance serotonergic transmission.
Ferrer
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Department of Neurochemistry, CID, Consejo Superior de Investigaciones Científicas, Barcelona, Spain.
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D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D015918:Infusion Pumps, Implantable; D007274:Injections, Intraperitoneal; D008297:Male; D017551:Microdialysis; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D014018:Tissue Distribution; D014191:Tranylcypromine / Q000008:administration & dosage / Q000494:pharmacology*
D012701:Serotonin; D014191:Tranylcypromine; D006897:Hydroxyindoleacetic Acid