Inhibition of both MAO-A and MAO-B required for the production of hypermotility in mice with the 5HT uptake inhibitors chlorimipramine and femoxetine.

Abstract Alone, the 5HT uptake inhibitors chlorimipramine (20 mg/kg s.c.) or femoxetine (20 mg/kg s.c.) had no effect on the motility of mice kept in a familiar cage. Similarly, pretreatment with clorgyline (a selective inhibitor of MAO-A), or l -deprenyl (a selective inhibitor of MAO-B) followed by administration of either of the 5HT pump blockers, had no effect on motility. However, pretreatment with a combination of clorgyline plus deprenyl, followed by either chlorimipramine or femoxetine, resulted in strong hypermotility. These results indicate that hypermotility seen after administration of a 5HT pump blocker to mice pretreated with a MAO inhibitor, depends on inhibition of both MAO-A and MAO-B, and is due to a high extraneuronal concentration of 5HT.