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Effects of elevated endogenous kynurenic acid on spatial working memory, contextual conditioning, and conditional learning.

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Call No.	Ph.D. 2006
Author	Chess, Amy C.
Title	Effects of elevated endogenous kynurenic acid on spatial working memory, contextual conditioning, and conditional learning.
Date	2006
Abstract	Kynurenic acid (KYNA) is produced and released by astrocytes, and acts as an α7-nicotinic acetylcholine receptor antagonist (at lower, physiological concentrations) and an antagonist of the glycine site of the NMDA receptor (at higher, nonphysiological concentrations). KYNA has recently been observed in elevated concentrations in schizophrenia and Alzheimer's Disease, and has been suggested to be associated with cognitive impairments in those disorders. The current studies tested the hypothesis that elevated endogenous KYNA disrupts cognitive abilities that depend on the formation of configural representations. Rats were given i.p. injections of L-kynurenine (L-KYN), the precursor of KYNA synthesis, two hours prior to training. Elevated KYNA disrupted spatial working memory in the radial arm maze, especially with increasing temporal delays. KYNA did not affect acquisition or expression of conditioned fear to the context or an explicit CS (tone), although KYNA facilitated extinction of the freezing response to the tone. Elevated KYNA retarded discrimination between two contexts differentiated by multiple contextual cues, an effect that was not likely due to enhanced acquisition of individual elements within each context. KYNA did not appear to affect acquisition of serial feature-negative discrimination in contrast, KYNA affected expression of this discrimination by decreasing responding on both Reinforced and Nonreinforced trials, but not affecting the basic ability to discriminate. These results suggest that elevated KYNA disrupted the formation of configural representations, but only when those representations involved spatial or contextual information. Implications for pathological states involving alterations of the kynurenine pathway, astrocyte contributions to synaptic plasticity, and nicotinic receptor mechanisms and behavior are discussed.
Description	ix, 137 leaves : ill. 28 cm.
Format	application/pdf
Advisor	David J. Bucci.
Subject	Kynurenine -- Derivatives. Cognition. Memory. Brain chemistry. Brain -- Pathophysiology -- Animal models.
College	Dartmouth College -- Department of Psychological and Brain Sciences.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.137

Title	Page 1
Format	application/pdf
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Full Text	EFFECTS OF ELEVATED ENDOGENOUS KYNURENIC ACID ON SPATIAL WORKING MEMORY, CONTEXTUAL CONDITIONING, & CONDITIONAL LEARNING A Thesis Submitted to the Faculty in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Psychological & Brain Sciences by Amy C. Chess DARTMOUTH COLLEGE Hanover, New Hampshire November 3, 2006 Examining Committee: ________________________ (chair) David J. Bucci, Ph.D. ________________________ Catherine P. Cramer, Ph.D. ________________________ James J. Hudziak, M.D. ________________________ Jeffrey S. Taube, Ph.D. _____________________ Charles K. Barlowe, Ph.D. Dean of Graduate Studies

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