Chronic studies were initiated in rats to determine the effects of high- and low-dose tranylcypromine (TCP) on 3Htryptamine (3H-T) binding sites. Male Sprague-Dawley rats were administered TCP (0.5 or 2.5 mg/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 point3H-T binding. Hippocampal3H-T binding was reduced after 10 and 28 days with the low dose and after 4, 10 and 28 days with the high dose. Striatal3H-T binding was reduced by both doses at all time intervals. The high dose resulted in a significantly greater reduction in striatal3H-T binding than did the low-dose after 4, 10, and 28 days. These results suggest that a more rapid reduction of3H-T binding in the hippocampus and/or a greater reduction of3H-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.
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