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.