EFFECTS OF COADMINISTRATION OF A MONOAMINE-OXIDASE INHIBITOR AND A 5-HT1A RECEPTOR ANTAGONIST ON 5-HYDROXYTRYPTAMINE CELL FIRING AND RELEASE

We report the effects of the monoamine oxidase inhibitor, tranylcyprom ine, combined with the 5-HT1A receptor antagonist, methoxyphenyl)-1-pi perazinyl]ethyl]-N-(2-pyridinyl cyclohexanecarboxamide (WAY 100635), o n both 5-hydroxytryptamine (5-HT) cell firing and cortical extracellul ar 5-HT in the rat. Tranylcypromine inhibited 5-HT cell firing in the dorsal raphe nucleus dose-dependently (ED(50) 5 mg/kg i.v.). In microd ialysis experiments, tranylcypromine (5 mg/kg i.v.) increased extracel lular 5-HT in the frontal cortex. WAY 100635 (0.1 mg/kg i.v.) both rev ersed the inhibition of 5-HT cell firing and facilitated the increase in extracellular 5-HT. In conclusion, WAY 100635 enhances the effect o f tranylcypromine on presynaptic 5-HT function. These data are relevan t to clinical evidence that co-therapy with a 5-HT1A receptor antagoni st improves the antidepressant efficacy of a monoamine oxidase inhibit or.