Kynurenic acid protects against the neurochemical and behavioral effects of unilateral quinolinic acid injections into the nucleus basalis of rats.
It has recently been demonstrated that kynurenic acid (KYN), an endogenous tryptophan metabolite, provides almost complete protection against the neurotoxic and mnemonic effects of another tryptophan metabolite quinolinic acid (QUIN) on the cell bodies of the nucleus basalis magnocellularis (nbm). The present study further investigated whether unilateral coinjections of KYN and QUIN into the rat nbm antagonized the effects of QUIN alone. Food-deprived rats were pretrained on an eight-arm radial maze, with four arms baited, until choice accuracy stabilized to greater than or equal to 87% correct. Postoperatively, rats were tested on the radial maze for 32 consecutive days. Feeding behavior and locomotor activity were also measured to determine if nonassociative factors accounted for any observed behavioral deficits. QUIN lesions resulted in significantly more working and reference memory errors compared with sham-operated and coinjected animals, which did not differ significantly from each other. There were no reliable group differences in amount of food eaten or locomotor activity. The QUIN group had a reliable decrease in cortical choline acetyltransferase, with no significant changes for the sham and coinjected groups. Results confirm that KYN antagonizes the neurotoxic and mnemonic effects of QUIN alone and suggest that the memory deficits induced by nbm lesions cannot be solely attributed to changes in feeding or locomotor activity.
Wirsching
B A
BA
Department of Psychology, Queen's University, Kingston, Ontario, Canada.
Beninger
R J
RJ
Jhamandas
K
K
Boegman
R J
RJ
Bialik
M
M
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000502:physiology*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D007736:Kynurenic Acid / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011725:Pyridines; D011805:Quinolinic Acids; D017378:Quinolinic Acid; D007736:Kynurenic Acid