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Reinstatement of episodic-like memory in rats by neurokinin-1 receptor antagonism.

Abstract
We previously showed that a systemic administration of the selective non-peptide neurokinin-1-receptor (NK-1-R) antagonist SR140333 increases hippocampal acetylcholine levels and facilitates long term memory. In the present study, we investigated whether systemic SR140333 has beneficial effects on episodic-like memory for unique experiences. Rats received either no injection, a vehicle injection or SR140333 at doses of 1, 3 and 9 mg/kg (i.p.) prior to the acquisition of an object memory for what, where and when. In line with previous results, untreated rats showed episodic-like memory, while vehicle-injected rats were impaired. A low dose of 1mg/kg SR140333 reinstated episodic-like memory. This result might be related to the effects of SR140333 on hippocampal cholinergic transmission and/or on the stress-response elicited by the injection procedure. Higher doses of SR140333 (3 and 9 mg/kg) induced psychomotor effects, including stereotypic behaviors and arched posture. Since NK-1-R antagonists have anxiolytic and promestic properties and induce hippocampal acetylcholine release at lower doses, they might be effective in the alleviation of the cognitive deficits and increased anxiety seen in early stages of Alzheimer's disease.
AuthorsEmriye Kart-Teke, Ekrem Dere, Marcus L Brandão, Joseph P Huston, Maria A De Souza Silva
JournalNeurobiology of learning and memory (Neurobiol Learn Mem) Vol. 87 Issue 3 Pg. 324-31 (Mar 2007) ISSN: 1074-7427 [Print] United States
PMID17079168 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Neurokinin-1 Receptor Antagonists
  • Piperidines
  • Quinuclidines
  • Receptors, Neurokinin-1
  • SR 140333
Topics
  • Alzheimer Disease (drug therapy, psychology)
  • Animals
  • Discrimination Learning (drug effects, physiology)
  • Dose-Response Relationship, Drug
  • Exploratory Behavior (drug effects, physiology)
  • Male
  • Memory (drug effects, physiology)
  • Motor Activity (drug effects, physiology)
  • Neurokinin-1 Receptor Antagonists
  • Piperidines (pharmacology)
  • Psychomotor Performance (drug effects, physiology)
  • Quinuclidines (pharmacology)
  • Rats
  • Rats, Wistar
  • Receptors, Neurokinin-1 (physiology)
  • Statistics, Nonparametric

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