[Abstract Title]. - Society for Neuroscience

Title: Contextual fear memory is impaired by administration of l-kynurenine prior to training
Authors: *A. M. LANDERS 1 , A. C. CHESS 2 , D. J. BUCCI 1 ;
1 Psychological & Brain Sci., Dartmouth Col., Hanover, NH; 2 Psychology, Univ. of Vermont,
Burlington, VT
Abstract: Kynurenic acid (KYNA) is synthesized and released exclusively by astrocytes and
acts as an antagonist at α7-nicotinic acetylcholine receptors and at higher non-physiological
concentrations, also antagonizes the glycine site of the NMDA receptor. KYNA is increased in
the brain tissue and cerebral spinal fluid of individuals with schizophrenia or Alzheimer‟s
disease. Both of these disorders are characterized by acetylcholine-mediated cognitive
impairments, suggesting the possibility that increases in cerebral KYNA may be associated with
specific cognitive dysfunction. Contextual learning, for example, has been shown to be
compromised in individuals with schizophrenia. Recent evidence indicates that nicotine
administration in rats enhances contextual conditioning but does not affect conditioning to a
discrete cue. In this study, we tested the hypothesis that elevations in KYNA concentration in
rats would selectively disrupt contextual conditioning while leaving conditioning to a discrete
conditioned stimulus (CS) unaffected. Endogenous KYNA concentration was increased by
administering l-kynurenine (LKYN), the precursor of KYNA. Previous studies have shown that a
100 mg/kg dose of LKYN is sufficient to produce a 4 fold increase in KYNA concentration. Rats
received i.p. injections of a vehicle solution or 100 mg/kg LKYN 2hr prior to training, which
consisted of 2 presentations of a 10-sec auditory CS (a 1500 Hz, 86 dB tone) paired with a
0.75mA, 500msec footshock. Twenty-four hours later, rats were returned to the training context
and were tested for freezing to the context. Twenty-four hours after the context test, rats were
placed in a novel context and were tested for freezing to the tone. Consistent with our hypothesis,
injections of LKYN did not affect acquisition of the conditioned freezing response during
training or the expression of conditioned freezing to the tone during the tone test session.
However, freezing during the context test session was significantly reduced in L-KYN-treated
rats. These data suggest that elevated levels of KYNA may contribute to contextual memory
deficits associated with certain forms of psychopathology.
Disclosures: A.M. Landers , None; A.C. Chess, None; D.J. Bucci, None.
Poster
291. Animal Cognition and Behavior: Learning and Memory: Pharmacology II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 291.20/SS3
Topic: F.02.j. Learning and memory: Pharmacology