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Prenatal kynurenine exposure in rats: age-dependent changes in NMDA receptor expression and conditioned fear responding

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Abstract

Rationale

Levels of kynurenic acid (KYNA), an endogenous negative modulator of alpha 7 nicotinic acetylcholine receptors (α7nAChRs) and antagonist at glutamatergic N-methyl-d-aspartate receptors (NMDARs), are elevated in the brain of patients with schizophrenia (SZ). In rats, dietary exposure to KYNA’s immediate precursor kynurenine during the last week of gestation produces neurochemical and cognitive deficits in adulthood that resemble those seen in patients with SZ.

Objectives

The present experiments examined whether prenatal kynurenine exposure results in age-dependent changes in the kynurenine pathway (KP), expression of selected receptors, and cognitive function.

Methods

Pregnant dams were fed unadulterated mash (progeny = ECON) or mash containing kynurenine (100 mg/day; progeny = EKYN) from embryonic day (ED) 15 to 22. Male offspring were assessed as juveniles, i.e., prior to puberty (postnatal day [PD] 32), or as adults (PD70) for brain KYNA levels, α7nAChR and NMDAR gene expression, and performance on a trace fear conditioning (TFC) task.

Results

KYNA levels were comparable between juvenile ECON and EKYN rats, whereas EKYN adults exhibited a ~3-fold increase in brain KYNA relative to ECONs. NR2A expression was persistently reduced (30–40 %) in EKYN rats at both ages. Compared to ECON adults, there was a 50 % reduction in NR1, and a trend toward decreased α7nAChR expression, in adult EKYN rats. Surprisingly, juvenile EKYN rats performed significantly better in the TFC paradigm than controls, whereas adult EKYN animals showed the predicted deficits.

Conclusions

Collectively, our results provide evidence that KP changes in the fetal brain alter neuronal development and cause age-dependent effects on neurochemistry and cognitive performance.

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Abbreviations

α7nACh:

alpha7 nicotinic acetylcholine

CS:

Conditioned stimulus

CSF:

Cerebrospinal fluid

ECON:

Embryonic control treatment

ED:

Embryonic day

EKYN:

Embryonic kynurenine treatment

KP:

Kynurenine pathway

KYNA:

Kynurenic acid

NMDA:

N-Methyl-d-aspartate

PD:

Postnatal day

PFC:

Prefrontal cortex

SZ:

Schizophrenia

TFC:

Trace fear conditioning

UCS:

Unconditioned stimulus

References

  • Abdel-Tawab GA, El-Zoghby SM, Saad AA (1975) Relationship between pyridoxal phosphate and some synthetic oestrogens, gonadotropin and thyroxine in their effects on kynurenine hydrolase and kynurenine aminotransferase enzymes of normal mouse liver. Acta Vitaminol Enzymol 29:326–331

    CAS  PubMed  Google Scholar 

  • Akagbosu CO, Evans GC, Gulick D, Suckow RF, Bucci DJ (2012) Exposure to kynurenic acid during adolescence produces memory deficits in adulthood. Schizophr Bull 38:769–778

    Article  PubMed  Google Scholar 

  • Akbarian S, Bunney WE Jr, Potkin SG, Wigal SB, Hagman JO, Sandman CA, Jones EG (1993) Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbances of cortical development. Arch Gen Psychiat 50:169–177

    Article  CAS  PubMed  Google Scholar 

  • Albuquerque EX, Schwarcz R (2013) Kynurenic acid as an antagonist of alpha7 nicotinic acetylcholine receptors in the brain: facts and challenges. Biochem Pharmacol 85:1027–1032

    Article  CAS  PubMed  Google Scholar 

  • Aoyama N, Takahashi N, Saito S, Maeno N, Ishihara R, Ji X, Miura H, Ikeda M, Suzuki T, Kitajima T, et al. (2006) Association study between kynurenine 3-monooxygenase gene and schizophrenia in the Japanese population. Genes Brain Behav 5:364–368

    Article  CAS  PubMed  Google Scholar 

  • Barnet RC, Hunt PS (2005) Trace and long-delay fear conditioning in the developing rat. Learn and Behav 33:437–443

    Article  Google Scholar 

  • Beggiato S, Tanganelli S, Fuxe K, Antonelli T, Schwarcz R, Ferraro L (2014) Endogenous kynurenic acid regulates extracellular GABA levels in the rat prefrontal cortex. Neuropharmacology 82:11–18

    Article  CAS  PubMed  Google Scholar 

  • Benes FM, Vincent SL, Todtenkopf M (2001) The density of pyramidal and nonpyramidal neurons in anterior cingulate cortex of schizophrenic and bipolar subjects. Biol Psychiat 50:395–406

    Article  CAS  PubMed  Google Scholar 

  • Brebion G, David AS, Jones HM, Ohlsen R, Pilowsky LS (2007) Temporal context discrimination in patients with schizophrenia: associations with auditory hallucinations and negative symptoms. Neuropsychologia 45:817–823

    Article  PubMed  Google Scholar 

  • Chess AC, Landers AM, Bucci DJ (2009) L-kynurenine treatment alters contextual fear conditioning and context discrimination but not cue-specific fear conditioning. Behav Brain Res 201:325–331

    Article  CAS  PubMed  Google Scholar 

  • Cui, Y., Jin, J., Zhang, X., Xu, H., Yang, L., Du, D., Zeng, Q., Tsien, J.Z., Yu, H., and Cao, X. (2011). Forebrain NR2B overexpression facilitating the prefrontal cortex long-term potentiation and enhancing working memory function in mice. PLoS One e20312

  • Danesch U, Gloss B, Schmid W, Schutz G, Schule R, Renkawitz R (1987) Glucocorticoid induction of the rat tryptophan oxygenase gene is mediated by two widely separated glucocorticoid-responsive elements. EMBO J 6:625–630

    CAS  PubMed  PubMed Central  Google Scholar 

  • Danesch U, Hashimoto S, Renkawitz R, Schutz G (1983) Transcriptional regulation of the tryptophan oxygenase gene in rat liver by glucocorticoids. J Biol Chem 258:4750–4753

    CAS  PubMed  Google Scholar 

  • Davis J, Eyre H, Jacka FN, Dodd S, Dean O, McEwen S, Debnath M, McGrath J, Maes M, Amminger P, et al. (2016) A review of vulnerability and risks for schizophrenia: beyond the two hit hypothesis. Neurosci Biobehav Rev 65:185–194

    Article  PubMed  PubMed Central  Google Scholar 

  • DeAngeli NE, Todd TP, Chang SE, Yeh HH, Yeh PW, Bucci DJ (2014) Exposure to kynurenic acid during adolescence increases sign-tracking and impairs long-term potentiation in adulthood. Front Behav Neurosci 8:451

    PubMed  Google Scholar 

  • Erhardt S, Blennow K, Nordin C, Skogh E, Lindstrom LH, Engberg G (2001) Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia. Neurosci Lett 313:96–98

    Article  CAS  PubMed  Google Scholar 

  • Erhardt S, Olsson SK, Engberg G (2009) Pharmacological manipulation of kynurenic acid: potential in the treatment of psychiatric disorders. CNS Drugs 23:91–101

    Article  CAS  PubMed  Google Scholar 

  • Erreger K, Dravid SM, Banke TG, Wyllie DJ, Traynelis SF (2005) Subunit-specific gating controls rat NR1/NR2A and NR1/NR2B NMDA channel kinetics and synaptic signalling profiles. J Phys 563:345–358

    CAS  Google Scholar 

  • Fanselow MS (1980) Conditional and unconditional components of post-shock freezing. Pavlovian J Biol Sci:177–182

  • Feinberg I (1982) Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? J Psychiat Res 17:319–334

    Article  PubMed  Google Scholar 

  • Flores-Barrera E, Thomases DR, Heng LJ, Cass DK, Caballero A, Tseng KY (2014) Late adolescent expression of GluN2B transmission in the prefrontal cortex is input-specific and requires postsynaptic protein kinase A and D1 dopamine receptor signaling. Biol Psychiat 75:508–516

    Article  CAS  PubMed  Google Scholar 

  • Forrest CM, Khalil OS, Pisar M, Darlington LG, Stone TW (2013) Prenatal inhibition of the tryptophan-kynurenine pathway alters synaptic plasticity and protein expression in the rat hippocampus. Brain Res 1504:1–15

    Article  CAS  PubMed  Google Scholar 

  • Forrest CM, McNair K, Pisar M, Khalil OS, Darlington LG, Stone TW (2015) Altered hippocampal plasticity by prenatal kynurenine administration, kynurenine-3-monoxygenase (KMO) deletion or galantamine. Neuroscience 310:91–105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gal EM, Sherman AD (1978) Synthesis and metabolism of L-kynurenine in rat brain. J Neurochem 30:607–613

    Article  CAS  PubMed  Google Scholar 

  • Gibney SM, Fagan EM, Waldron AM, O’Byrne J, Connor TJ, Harkin A (2014) Inhibition of stress-induced hepatic tryptophan 2,3-dioxygenase exhibits antidepressant activity in an animal model of depressive behaviour. Int J Neuropsychopharmacol 17:917–928

    Article  CAS  PubMed  Google Scholar 

  • Gilmartin MR, Balderston NL, Helmstetter FJ (2014) Prefrontal cortical regulation of fear learning. Trends Neurosci 37:455–464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gilmartin MR, Kwapis JL, Helmstetter FJ (2013) NR2A- and NR2B-containing NMDA receptors in the prelimbic medial prefrontal cortex differentially mediate trace, delay, and contextual fear conditioning. Learn Memory 20:290–294

    Article  CAS  Google Scholar 

  • Gilmartin MR, McEchron MD (2005) Single neurons in the medial prefrontal cortex of the rat exhibit tonic and phasic coding during trace fear conditioning. Behav Neurosci 119:1496–1510

    Article  PubMed  Google Scholar 

  • Giza CC, Maria NS, Hovda DA (2006) N-Methyl-D-aspartate receptor subunit changes after traumatic injury to the developing brain. J Neurotraum 23:950–961

    Article  Google Scholar 

  • Glausier JR, Lewis DA (2013) Dendritic spine pathology in schizophrenia. Neuroscience 251:90–107

    Article  CAS  PubMed  Google Scholar 

  • Goodfellow MJ, Abdulla KA, Lindquist DH (2016) Neonatal ethanol exposure impairs trace fear conditioning and alters NMDA receptor subunit expression in adult male and female rats. Alcohol Clin Exp Res 40:309–318

    Article  CAS  PubMed  Google Scholar 

  • Gramsbergen JB, Hodgkins PS, Rassoulpour A, Turski WA, Guidetti P, Schwarcz R (1997) Brain-specific modulation of kynurenic acid synthesis in the rat. J Neurochem 69:290–298

    Article  CAS  PubMed  Google Scholar 

  • Green MF (1996) What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiat 153:321–330

    Article  CAS  PubMed  Google Scholar 

  • Green MF, Kern RS, Heaton RK (2004) Longitudinal studies of cognition and functional outcome in schizophrenia: implications for MATRICS. Schizophr Res 72:41–51

    Article  PubMed  Google Scholar 

  • Hashimoto K (2014) Targeting of NMDA receptors in new treatments for schizophrenia. Expert Opin Ther Targets 18:1049–1063

    Article  CAS  PubMed  Google Scholar 

  • Hemsley DR (2005) The schizophrenic experience: taken out of context? Schizophr Bull 31:43–53

    Article  PubMed  Google Scholar 

  • Jansson LC, Akerman KE (2014) The role of glutamate and its receptors in the proliferation, migration, differentiation and survival of neural progenitor cells. J Neural Transm 121:819–836

    Article  CAS  PubMed  Google Scholar 

  • Kegel ME, Bhat M, Skogh E, Samuelsson M, Lundberg K, Dahl ML, Sellgren C, Schwieler L, Engberg G, Schuppe-Koistinen I, et al. (2014) Imbalanced kynurenine pathway in schizophrenia. Int J Tryptophan Res 7:15–22

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kessler M, Terramani T, Lynch G, Baudry M (1989) A glycine site associated with N-methyl-D-aspartic acid receptors: characterization and identification of a new class of antagonists. J Neurochem 52:1319–1328

    Article  CAS  PubMed  Google Scholar 

  • King EC, Pattwell SS, Glatt CE, Lee FS (2014) Sensitive periods in fear learning and memory. Stress 17:13–21

    Article  CAS  PubMed  Google Scholar 

  • Konradsson-Geuken A, Gash CR, Alexander K, Pomerleau F, Huettl P, Gerhardt GA, Bruno JP (2009) Second-by-second analysis of alpha 7 nicotine receptor regulation of glutamate release in the prefrontal cortex of awake rats. Synapse 63:1069–1082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Konradsson-Geuken A, Wu HQ, Gash CR, Alexander KS, Campbell A, Sozeri Y, Pellicciari R, Schwarcz R, Bruno JP (2010) Cortical kynurenic acid bi-directionally modulates prefrontal glutamate levels as assessed by microdialysis and rapid electrochemistry. Neuroscience 169:1848–1859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lewis DA (1997) Development of the prefrontal cortex during adolescence: insights into vulnerable neural circuits in schizophrenia. Neuropsychopharmacol 16:385–398

    Article  CAS  Google Scholar 

  • Lin H, Hsu FC, Baumann BH, Coulter DA, Anderson SA, Lynch DR (2014a) Cortical parvalbumin GABAergic deficits with alpha7 nicotinic acetylcholine receptor deletion: implications for schizophrenia. Mol Cell Neurosci 61:163–175

    Article  CAS  PubMed  Google Scholar 

  • Lin H, Hsu FC, Baumann BH, Coulter DA, Lynch DR (2014b) Cortical synaptic NMDA receptor deficits in alpha7 nicotinic acetylcholine receptor gene deletion models: implications for neuropsychiatric diseases. Neurobiol Dis 63:129–140

    Article  CAS  PubMed  Google Scholar 

  • Linderholm KR, Skogh E, Olsson SK, Dahl ML, Holtze M, Engberg G, Samuelsson M, Erhardt S (2012) Increased levels of kynurenine and kynurenic acid in the CSF of patients with schizophrenia. Schizophr Bull 38:426–432

    Article  PubMed  Google Scholar 

  • McGinty F, Rose DP (1969) Influence of androgens upon tryptophan metabolism in man. Life Sci 8:1193–1199

    Article  CAS  PubMed  Google Scholar 

  • Millan MJ, Agid Y, Brune M, Bullmore ET, Carter CS, Clayton NS, Connor R, Davis S, Deakin B, DeRubeis RJ, et al. (2012) Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat Rev Drug Discov 11:141–168

    Article  CAS  PubMed  Google Scholar 

  • Miller CL, Llenos IC, Dulay JR, Barillo MM, Yolken RH, Weis S (2004) Expression of the kynurenine pathway enzyme tryptophan 2,3-dioxygenase is increased in the frontal cortex of individuals with schizophrenia. Neurobiol Dis 15:618–629

    Article  CAS  PubMed  Google Scholar 

  • Nielsen DM, Crnic LS (2002) Automated analysis of foot-shock sensitivity and concurrent freezing behavior in mice. J Neurosci Meth 115:199–209

    Article  Google Scholar 

  • Notarangelo FM, Pocivavsek A (2016) Elevated kynurenine pathway metabolism during neurodevelopment: implications for brain and behavior. Neuropharmacology doi 10:1016

    Google Scholar 

  • O’Donnell P (2011) Adolescent onset of cortical disinhibition in schizophrenia: insights from animal models. Schizophr Bull 37:484–492

    Article  PubMed  PubMed Central  Google Scholar 

  • Ohgi Y, Futamura T, Hashimoto K (2015) Glutamate signaling in synaptogenesis and NMDA receptors as potential therapeutic targets for psychiatric disorders. Curr Mol Med 15:206–221

    Article  CAS  PubMed  Google Scholar 

  • Pattwell SS, Duhoux S, Hartley CA, Johnson DC, Jing D, Elliott MD, Ruberry EJ, Powers A, Mehta N, Yang RR, et al. (2012) Altered fear learning across development in both mouse and human. PNAS USA 109:16318–16323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perkins MN, Stone TW (1982) An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid. Brain Res 247:184–187

    Article  CAS  PubMed  Google Scholar 

  • Pershing ML, Bortz DM, Pocivavsek A, Fredericks PJ, Jorgensen CV, Vunck SA, Leuner B, Schwarcz R, Bruno JP (2015) Elevated levels of kynurenic acid during gestation produce neurochemical, morphological, and cognitive deficits in adulthood: implications for schizophrenia. Neuropharmacology 90:33–41

    Article  CAS  PubMed  Google Scholar 

  • Pocivavsek A, Notarangelo FM, Wu HQ, Bruno JP, Schwarcz R (2016) Astrocytes as pharmacological targets in the treatment of schizophrenia: focus on kynurenic acid. In: Pletnikov M, Waddington J (eds) Modeling the psychopathological dimensions of schizophrenia. Academic Press, New York, pp. 423–443

    Google Scholar 

  • Pocivavsek A, Thomas MA, Elmer GI, Bruno JP, Schwarcz R (2014) Continuous kynurenine administration during the prenatal period, but not during adolescence, causes learning and memory deficits in adult rats. Psychopharm 231:2799–2809

    Article  CAS  Google Scholar 

  • Rao PK, Kumar RM, Farkhondeh M, Baskerville S, Lodish HF (2006) Myogenic factors that regulate expression of muscle-specific microRNAs. PNAS USA 103:8721–8726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raybuck JD, Gould TJ (2010) The role of nicotinic acetylcholine receptors in the medial prefrontal cortex and hippocampus in trace fear conditioning. Neurobiol Learn Mem 94:353–363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rimol LM, Hartberg CB, Nesvag R, Fennema-Notestine C, Hagler DJ Jr, Pung CJ, Jennings RG, Haukvik UK, Lange E, Nakstad PH, et al. (2010) Cortical thickness and subcortical volumes in schizophrenia and bipolar disorder. Biol Psychiat 68:41–50

    Article  PubMed  Google Scholar 

  • Sathyasaikumar KV, Stachowski EK, Wonodi I, Roberts RC, Rassoulpour A, McMahon RP, Schwarcz R (2011) Impaired kynurenine pathway metabolism in the prefrontal cortex of individuals with schizophrenia. Schizophr Bull 37:1147–1156

    Article  PubMed  Google Scholar 

  • Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3:1101–1108

    Article  CAS  PubMed  Google Scholar 

  • Schwarcz R, Bruno JP, Muchowski PJ, Wu HQ (2012) Kynurenines in the mammalian brain: when physiology meets pathology. Nat Rev: Neurosci 13:465–477

    Article  CAS  Google Scholar 

  • Schwarcz R, Rassoulpour A, Wu HQ, Medoff D, Tamminga CA, Roberts RC (2001) Increased cortical kynurenate content in schizophrenia. Biol Psychiat 50:521–530

    Article  CAS  PubMed  Google Scholar 

  • Selemon LD, Zecevic N (2015) Schizophrenia: a tale of two critical periods for prefrontal cortical development. Transl Psychiatry 5:e623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shouval HZ, Bear MF, Cooper LN (2002) A unified model of NMDA receptor-dependent bidirectional synaptic plasticity. PNAS USA 99:10831–10836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stone TW, Darlington LG (2013) The kynurenine pathway as a therapeutic target in cognitive and neurodegenerative disorders. Brit J Pharmacol 169:1211–1227

    Article  CAS  Google Scholar 

  • Tang YP, Shimizu E, Dube GR, Rampon C, Kerchner GA, Zhuo M, Liu G, Tsien JZ (1999) Genetic enhancement of learning and memory in mice. Nature 401:63–69

    Article  CAS  PubMed  Google Scholar 

  • Thomsen MS, Mikkelsen JD (2012) The alpha7 nicotinic acetylcholine receptor complex: one, two or multiple drug targets? Curr Drug Targets 13:707–720

    Article  CAS  PubMed  Google Scholar 

  • Vasey MW, Thayer JF (1987) The continuing problem of false positives in repeated measures ANOVA in psychophysiology: a multivariate solution. Psychophysiology 24:479–486

    Article  CAS  PubMed  Google Scholar 

  • Wang H, Stradtman GG, Wang XJ, Gao WJ (2008) A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex. PNAS USA 105:16791–16796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang M, Yang Y, Wang CJ, Gamo NJ, Jin LE, Mazer JA, Morrison JH, Wang XJ, Arnsten AF (2013) NMDA receptors subserve persistent neuronal firing during working memory in dorsolateral prefrontal cortex. Neuron 77:736–749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Waters FA, Maybery MT, Badcock JC, Michie PT (2004) Context memory and binding in schizophrenia. Schizophr Res 68:119–125

    Article  PubMed  Google Scholar 

  • Wonodi I, Stine OC, Sathyasaikumar KV, Roberts RC, Mitchell BD, Hong LE, Kajii Y, Thaker GK, Schwarcz R (2011) Downregulated kynurenine 3-monooxygenase gene expression and enzyme activity in schizophrenia and genetic association with schizophrenia endophenotypes. Arch Gen Psychiat 68:665–674

    Article  CAS  PubMed  Google Scholar 

  • Wright IC, Rabe-Hesketh S, Woodruff PW, David AS, Murray RM, Bullmore ET (2000) Meta-analysis of regional brain volumes in schizophrenia. Am J Psychiat 157:16–25

    Article  CAS  PubMed  Google Scholar 

  • Wu HQ, Okuyama M, Kajii Y, Pocivavsek A, Bruno JP, Schwarcz R (2014) Targeting kynurenine aminotransferase II in psychiatric diseases: promising effects of an orally active enzyme inhibitor. Schizophr Bull 40(Suppl 2):S152–S158

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu HQ, Pereira EF, Bruno JP, Pellicciari R, Albuquerque EX, Schwarcz R (2010) The astrocyte-derived alpha7 nicotinic receptor antagonist kynurenic acid controls extracellular glutamate levels in the prefrontal cortex. J Mol Neurosci 40:204–210

    Article  CAS  PubMed  Google Scholar 

  • Xu Z, Chen RQ, Gu QH, Yan JZ, Wang SH, Liu SY, Lu W (2009) Metaplastic regulation of long-term potentiation/long-term depression threshold by activity dependent changes of NR2A/NR2B ratio. J Neurosci 29:10

    Google Scholar 

  • Yashiro K, Philpot B (2008) Regulation of NMDA receptor subunit expression and its implications for LTD, LTP, and metaplasticity. Neuropharmacology 55:14

    Article  Google Scholar 

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Acknowledgments

This study was supported by NIMH grants MH083729 (to JPB and RS) and P50103222 (to RS). AP is supported by NIH grant K12 HD43489-14.

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Authors and Affiliations

  1. Department of Psychology, The Ohio State University, Columbus, OH, USA

    Michelle L. Pershing, Derick H. Lindquist & John P. Bruno

  2. Department of Neuroscience, The Ohio State University, Columbus, OH, USA

    David Phenis, Derick H. Lindquist & John P. Bruno

  3. Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy

    Valentina Valentini

  4. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA

    Ana Pocivavsek & Robert Schwarcz

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  1. Michelle L. Pershing
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  2. David Phenis
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Correspondence to John P. Bruno.

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Pershing, M.L., Phenis, D., Valentini, V. et al. Prenatal kynurenine exposure in rats: age-dependent changes in NMDA receptor expression and conditioned fear responding. Psychopharmacology 233, 3725–3735 (2016). https://doi.org/10.1007/s00213-016-4404-9

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