Effects of low- and high-dose tranylcypromine on [3H]tryptamine binding sites in the rat hippocampus and striatum.
Chronic studies were initiated in rats to determine the effects of high- and low-dose tranylcypromine (TCP) on [3H]tryptamine (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 point 3H-T binding. Hippocampal 3H-T binding was reduced after 10 and 28 days with the low dose and after 4, 10 and 28 days with the high dose. Striatal 3H-T binding was reduced by both doses at all time intervals. The high dose resulted in a significantly greater reduction in striatal 3H-T binding than did the low-dose after 4, 10, and 28 days. These results suggest that a more rapid reduction of 3H-T binding in the hippocampus and/or a greater reduction of 3H-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.
Goodnough
D B
DB
Department of Psychiatry, University of Alberta, Edmonton, Canada.
Baker
G B
GB
Mousseau
D D
DD
Greenshaw
A J
AJ
Dewhurst
W G
WG
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002408:Catheters, Indwelling; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D013997:Time Factors; D014191:Tranylcypromine / Q000008:administration & dosage / Q000494:pharmacology*; D014316:Tritium; D014363:Tryptamines / Q000378:metabolism*
D007527:Isoenzymes; D011985:Receptors, Serotonin; D014363:Tryptamines; D014316:Tritium; D014191:Tranylcypromine; C030820:tryptamine; D008995:Monoamine Oxidase