EFFECTS OF LOW-DOSE AND HIGH-DOSE TRANYLCYPROMINE ON [H-3] TRYPTAMINEBINDING-SITES IN THE RAT HIPPOCAMPUS AND STRIATUM

Chronic studies were initiated in rats to determine the effects of hig h- and low-dose tranylcypromine (TCP) on [H-3]tryptamine (H-3-T) bindi ng sites. Male Sprague-Dawley rats were administered TCP (0.5 or 2.5 m g/kg/day) or vehicle (distilled water) for 4, 10 or 28 days via Alzet minipumps. After decapitation, the hippocampus and striatum were used to prepare membrane fragments for single point H-3-T binding. Hippocam pal H-3-T binding was reduced after 10 and 28 days with the low dose a nd after 4, 10 and 28 days with the high dose. Striatal H-3-T binding was reduced by both doses at all time intervals. The high dose resulte d in a significantly greater reduction in striatal H-3-T binding than did the low-dose after 4, 10, and 28 days. These results suggest that a more rapid reduction of H-3-T binding in the hippocampus and/or a gr eater reduction of H-3-T binding in the striatum by high-dose TCP than by low-dose TCP may be contributing factors in the reported efficacy of the former in refractory depression.