Monoamine oxidase inhibitors increase preferentially extracellular 5-hydroxytryptamine in the midbrain raphe nuclei. A brain microdialysis study in the awake rat.

We have examined the local and systemic effects of clorgyline, tranylcypromine and deprenyl on extracellular serotonin (5-HT) and 5-hydroxyindoleacetic acid in the raphe nuclei and in frontal cortex of awake, freely-moving rats using microdialysis. When administered through the dialysis probe, monoamine oxidase (monoamine: oxygen oxidoreductase (deaminating), E.C. 1.4.3.4., MAO) inhibitors increased 5-HT output in a dose-dependent manner in both brain areas. The effects were more pronounced in the raphe nuclei for the three MAO inhibitors at all doses assayed. When the monoamine oxidase inhibitors were given i.p., dialysate 5-HT increased dramatically, after tranylcypromine (15 mg/kg), in raphe nuclei and frontal cortex (area under the curve (AUC) to 4 h post-treatment: 63-fold and 11-fold, respectively) whereas the effects of clorgyline (10 mg/kg) were much less pronounced (+47% increase in the AUC for raphe nuclei, P < 0.09; +18% increase in the AUC for frontal cortex, n.s.). Deprenyl (2.5 mg/kg, i.p.) induced a moderate (+22%) increase of dialysate 5-HT from the raphe nuclei but did not cause a change in dialysate 5-HT from the frontal cortex (+4%). However, clorgyline, or deprenyl, dramatically increased dialysate 5-HT in animals which had been pre-treated with the above dose of deprenyl, or clorgyline, respectively, showing that the blockade of both forms of MAO results in much larger increases of extracellular 5-HT than does the blockade of either form alone.(ABSTRACT TRUNCATED AT 250 WORDS)