Early developmental elevations of brain kynurenic acid impair cognitive flexibility in adults: Reversal with galantamine

• Published in: Neuroscience Vol. 238; pp. 19 - 28
• Main Authors: Alexander, K.S, Pocivavsek, A, Wu, H.-Q, Pershing, M.L, Schwarcz, R, Bruno, J.P
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 15.05.2013
• Subjects: Animals; Attention - drug effects; Attention - physiology; Brain - drug effects; Brain - metabolism; Brain - physiopathology; Cognition - drug effects; Female; Galantamine - pharmacology; glutamate; Glutamic Acid - metabolism; Kynurenic Acid - metabolism; kynurenine; Kynurenine - pharmacology; Male; Neurology; Nootropic Agents - pharmacology; prefrontal cortex; Pregnancy; Prenatal Exposure Delayed Effects - metabolism; Rats; Rats, Wistar; schizophrenia; Set (Psychology); set-shifting; α7 nicotinic receptors; devKYN; KYNA; REV; compound discrimination; ACh; gestational day; prefrontal cortex; Schizophrenia; kynurenine; N-methyl- d-aspartic acid; PFC; OFC; SD; simple discrimination; analysis of variance; ANOVA; NMDA; orbitofrontal cortex; postnatal day; ID; extra-dimensional shift; GD; glutamate; ED; CD; SZ; developmental control treatment; devCTL; set-shifting; α7 nicotinic receptors; reversal; α7nAChR; GAL; PD; galantamine treatment; developmental kynurenine treatment; NMDAR; acetylcholine; intra-dimensional shift; NMDA receptor; kynurenic acid; α7 nicotinic acetylcholine receptor; schizophrenia
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2013.01.063

Highlights ► A novel neurodevelopmental animal model of schizophrenia is presented. ► Developmental kynurenine treatment results in elevated KYNA levels into adulthood. ► Adults with elevated KYNA levels during development exhibit deficits in cognitive flexibility. ► These cognitive deficits are ameliorated by acute treatment with galantamine.