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

Abstract
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.
AuthorsA Horita, M A Carino, J Zabawska, H Lai
JournalPeptides (Peptides) 1989 Jan-Feb Vol. 10 Issue 1 Pg. 121-4 ISSN: 0196-9781 [Print] United States
PMID2501767 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antidepressive Agents
  • Thiazolidines
  • Ibotenic Acid
  • Thyrotropin-Releasing Hormone
  • pyro(l-alpha-aminoadipyl)-L-histidyl-L-thiazolidine-4-carboxamide
  • Choline O-Acetyltransferase
Topics
  • Animals
  • Antidepressive Agents (pharmacology)
  • Choline O-Acetyltransferase (metabolism)
  • Hippocampus (drug effects, enzymology, physiology)
  • Ibotenic Acid (pharmacology)
  • Learning (drug effects)
  • Male
  • Rats
  • Rats, Inbred Strains
  • Reference Values
  • Thiazolidines
  • Thyrotropin-Releasing Hormone (analogs & derivatives, pharmacology)

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