Antidepressive and antihypertensive effects of MAO-A inhibition: role of N-acetylserotonin. A review

Abstract

Acute administration of irreversible and reversible selective MAO-A inhibitors and high doses (or chronic administration of low doses) of relatively selective MAO-B inhibitors (but not of highly selective MAO-B inhibitors) suppressed MAO-A activity and stimulated N-acetylation of pineal serotonin into N-acetylserotonin, the immediate precursor of melatonin. Consequent increase of melatonin occurs only in > 21-days-old rats. The effect is strain (spontaneously hypertensive rats > Fisher344N > Wistar Kyoto > Sprague-Dawley) and gender (male > female) dependent. N-acetylserotonin increase after clorgyline was weaker in the light-primed aged (or young animals with lesioned suprachiasmatic nuclei) than in young intact or sham-operated rats. N-acetylserotonin increase after MAO-A inhibitors might mediate their antidepressive (N-acetylserotonin and melatonin exerted antidepressant-like activity in the mouse tail-suspension and frog tests) and antihypertensive effects (N-acetylserotonin, but not melatonin, decreased blood pressure in spontaneously hypertensive rats).