Chronic MAO A and MAO B inhibition decreases the 5-HT1A receptor-mediated inhibition of forskolin-stimulated adenylate cyclase

The effect of chronic administration of various monoamine oxidase (MAO) inhibitors on the ability of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) to inhibit forskolin-stimulated adenylate cyclase activity was studied. Groups of 12 rats were given either saline, (E)-beta-fluoromethylene-m-tyrosine (MDL 72394 0.25 mg/kg p.o.), clorgyline (1 mg/kg p.o.), selegiline (1 mg/kg p.o.) or tranylcypromine (5 mg/kg p.o.) once a day for 21 days. Biochemical determinations were made 72 h after the final dose. MDL 72394 and tranylcypromine produced a nonselective inhibition of MAO but clorgyline and selegiline selectively inhibited MAO A and MAO B respectively. All treatments that inhibited MAO A also increased tissue levels of 5-HT. Chronic treatment with MDL 72394, clorgyline or tranylcypromine reduced the ability of 8-OH-DPAT to inhibit forskolin-stimulated adenylate cyclase activity. These data suggest that chronic nonselective and chronic MAO A inhibition causes a down-regulation of the 5-HT1A-mediated inhibition of forskolin-stimulated adenylate cyclase activity.