TRH analog MK-771 reverses neurochemical and learning deficits in medial septal-lesioned rats.
Microinjection of ibotenic acid into medial septum of rats decreased choline acetyltransferase (CAT) and high-affinity choline uptake (HACU) activities in hippocampus and retarded the learning of a spatial memory task in the radial-arm maze. Administration of MK-771, a stable TRH analog, to such animals restored HACU activity in hippocampus to normal levels. Daily treatment of rats with MK-771 prior to maze running also restored the animals' learning ability. MK-771 did not enhance hippocampal HACU activity or maze performance in sham-lesioned rats. These results suggest that MK-771 reversed the ibotenic acid-induced memory deficit by restoring septohippocampal cholinergic function. MK-771 and other TRH analogs may represent novel agents for improving memory deficits produced by cholinergic insufficiency in Alzheimer's disease.
Horita
A
A
Department of Pharmacology, School of Medicine, University of Washington, Seattle 98195.
Carino
M A
MA
Zabawska
J
J
Lai
H
H
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D007051:Ibotenic Acid / Q000494:pharmacology; D007858:Learning / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D053778:Thiazolidines; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology
D000928:Antidepressive Agents; D053778:Thiazolidines; D007051:Ibotenic Acid; D013973:Thyrotropin-Releasing Hormone; C021597:pyro(l-alpha-aminoadipyl)-L-histidyl-L-thiazolidine-4-carboxamide; D002795:Choline O-Acetyltransferase