Combined treatment with MAO-A inhibitor and MAO-B inhibitor increases extracellular noradrenaline levels more than MAO-A inhibitor alone through increases in β-phenylethylamine

Monoamine oxidase inhibitors (MAO inhibitors) have been widely used as antidepressants. However, it remains unclear whether a difference exists between non-selective MAO inhibitors and selective MAO-A inhibitors in terms of their antidepressant effects. Using in vivo microdialysis methods, we measured extracellular noradrenaline and serotonin levels following administration of Ro 41-1049, a reversible MAO-A inhibitor and/or lazabemide, a reversible MAO-B inhibitor in the medial prefrontal cortex (mPFC) of rats. We examined the effect of local infusion of β-phenylethylamine to the mPFC of rats on extracellular noradrenaline and serotonin levels. Furthermore, the concentrations of β-phenylethylamine in the tissue of the mPFC after combined treatment with Ro 41-1049 and lazabemide were measured. The Ro 41-1049 alone and the combined treatment significantly increased extracellular noradrenaline levels compared with vehicle and lazabemide alone. Furthermore, the combined treatment increased noradrenaline levels significantly more than Ro 41-1049 alone did. The Ro 41-1049 alone and the combined treatment significantly increased extracellular serotonin levels compared with vehicle and lazabemide alone, but no difference in serotonin levels was found between the combined treatment group and the Ro 41-1049 group. Local infusion of low-dose β-phenylethylamine increased extracellular noradrenaline levels, but not that of serotonin. Only the combined treatment significantly increased β-phenylethylamine levels in tissues of the mPFC. Our results suggest that the combined treatment with a MAO-A inhibitor and a MAO-B inhibitor strengthens antidepressant effects because the combined treatment increases extracellular noradrenaline levels more than a MAO-A inhibitor alone through increases in β-phenylethylamine.