TRH analog MK-771 reverses neurochemical and learning deficits in medial septal-lesioned rats.

Article date: 1989/1/1

PubMed ID: 2501767

Journal name: Peptides (ISSN: 0196-9781)


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.

Author List: Horita A, Carino M A, Zabawska J, Lai H

Publication Types: Journal Article; Research Support, U.S. Gov't, P.H.S.

Substances mentioned in the article: Antidepressive Agents; Thiazolidines; Ibotenic Acid; Thyrotropin-Releasing Hormone; pyro(l-alpha-aminoadipyl)-L-histidyl-L-thiazolidine-4-carboxamide; Choline O-Acetyltransferase;

Mesh terms: Animals; Antidepressive Agents/pharmacology; Choline O-Acetyltransferase/metabolism; Hippocampus/drug effects; Ibotenic Acid/pharmacology; Learning/drug effects; Male; Rats; Rats, Inbred Strains; Reference Values; Thiazolidines; Thyrotropin-Releasing Hormone/analogs & derivatives;

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