Sustained NMDA receptor hypofunction impairs brain-derived neurotropic factor signalling in the PFC,but not in the hippocampus,and disturbs PFC-dependent cognition in mice
Restricted accessResearch articleFirst published online June, 2021
Sustained NMDA receptor hypofunction impairs brain-derived neurotropic factor signalling in the PFC,but not in the hippocampus,and disturbs PFC-dependent cognition in mice
Cognitive deficits profoundly impact on the quality of life of patients with schizophrenia. Alterations in brain derived neurotrophic factor (BDNF) signalling, which regulates synaptic function through the activation of full-length tropomyosin-related kinase B receptors (TrkB-FL), are implicated in the aetiology of schizophrenia, as is N-methyl-D-aspartate receptor (NMDA-R) hypofunction. However, whether NMDA-R hypofunction contributes to the disrupted BDNF signalling seen in patients remains unknown.
Aims:
The purpose of this study was to characterise BDNF signalling and function in a preclinical rodent model relevant to schizophrenia induced by prolonged NMDA-R hypofunction.
Methods:
Using the subchronic phencyclidine (PCP) model, we performed electrophysiology approaches, molecular characterisation and behavioural analysis.
Results:
The data showed that prolonged NMDA-R antagonism, induced by subchronic PCP treatment, impairs long-term potentiation (LTP) and the facilitatory effect of BDNF upon LTP in the medial prefrontal cortex (PFC) of adult mice. Additionally, TrkB-FL receptor expression is decreased in the PFC of these animals. By contrast, these changes were not present in the hippocampus of PCP-treated mice. Moreover, BDNF levels were not altered in the hippocampus or PFC of PCP-treated mice. Interestingly, these observations are paralleled by impaired performance in PFC-dependent cognitive tests in mice treated with PCP.
Conclusions:
Overall, these data suggest that NMDA-R hypofunction induces dysfunctional BDNF signalling in the PFC, but not in the hippocampus, which may contribute to the PFC-dependent cognitive deficits seen in the subchronic PCP model. Additionally, these data suggest that targeting BDNF signalling may be a mechanism to improve PFC-dependent cognitive dysfunction in schizophrenia.
AhmedAOMantiniAMFridbergDJ, et al. (2015) Brain-derived neurotrophic factor (BDNF) and neurocognitive deficits in people with schizophrenia: A meta-analysis. Psychiatry Res226: 1–13. DOI: 10.1016/j.psychres.2014.12.069.
2.
AlbensiBCOliverDRToupinJ, et al. (2007) Electrical stimulation protocols for hippocampal synaptic plasticity and neuronal hyper-excitability: Are they effective or relevant?Exp Neurol204: 1–13. DOI: 10.1016/j.expneurol.2006.12.009.
3.
AmaniMSamadiHDoostiM-H, et al. (2013) Neonatal NMDA receptor blockade alters anxiety- and depression-related behaviors in a sex-dependent manner in mice. Neuropharmacology73: 87–97. DOI: 10.1016/j.neuropharm.2013.04.056.
4.
AmitaiNKuczenskiRBehrensMM, et al. (2012) Repeated phencyclidine administration alters glutamate release and decreases GABA markers in the prefrontal cortex of rats. Neuropharmacology62: 1422–1431. DOI: 10.1016/j.neuropharm.2011.01.008.
5.
AnastasioNCJohnsonKM (2008) Differential regulation of the NMDA receptor by acute and sub-chronic phencyclidine administration in the developing rat. J Neurochem104: 1210–1218. DOI: 10.1111/j.1471-4159.2007.05047.x.
6.
AndersonWWCollingridgeGL (2007) Capabilities of the WinLTP data acquisition program extending beyond basic LTP experimental functions. J Neurosci Methods162: 346–356. DOI: 10.1016/j.jneumeth.2006.12.018.
7.
AndrewsJLNewellKAMatosinN, et al. (2018) Perinatal administration of phencyclidine alters expression of Lingo-1 signaling pathway proteins in the prefrontal cortex of juvenile and adult rats. Neuronal Signal2: NS20180059. DOI: 10.1042/NS20180059.
8.
AntunesMBialaG (2012) The novel object recognition memory: Neurobiology, test procedure, and its modifications. Cogn Process13: 93–110. DOI: 10.1007/s10339-011-0430-z.
9.
Asif-MalikADautanDYoungAMJ, et al. (2017) Altered cortico-striatal crosstalk underlies object recognition memory deficits in the sub-chronic phencyclidine model of schizophrenia. Brain Struct Funct222: 3179–3190. DOI: 10.1007/s00429-017-1393-3.
10.
AudetM-CGouletSDoréFY (2009) Impaired social motivation and increased aggression in rats subchronically exposed to phencyclidine. Physiol Behav96: 394–398. DOI: 10.1016/j.physbeh.2008.11.002.
BarkerGRIBirdFAlexanderV, et al. (2007) Recognition memory for objects, place, and temporal order: A disconnection analysis of the role of the medial prefrontal cortex and perirhinal cortex. J Neurosci27: 2948–2957. DOI: 10.1523/JNEUROSCI.5289-06.2007.
13.
BarkerGRIWarburtonEC (2011) When is the hippocampus involved in recognition memory?J Neurosci31: 10721–10731. DOI: 10.1523/JNEUROSCI.6413-10.2011.
BlissTVCollingridgeGL (1993) A synaptic model of memory: Long-term potentiation in the hippocampus. Nature361: 31–39. DOI: 10.1038/361031a0.
16.
Bruins SlotLAKlevenMSNewman-TancrediA (2005) Effects of novel antipsychotics with mixed D2 antagonist/5-HT1A agonist properties on PCP-induced social interaction deficits in the rat. Neuropharmacology49: 996–1006. DOI: 10.1016/j.neuropharm.2005.05.013.
17.
ByeCMMcDonaldRJ (2019) A specific role of hippocampal NMDA receptors and arc protein in rapid encoding of novel environmental representations and a more general long-term consolidation function. Front Behav Neurosci13: 8. DOI: 10.3389/fnbeh.2019.00008.
18.
CengotitabengoaMMAlberichSParelladaM, et al. (2019) Evolution of BDNF full-length/truncated receptor ratio and cognitive/general functioning after a first episode of psychosis. Neuropsychiatry9. DOI: 10.4172/Neuropsychiatry.1000561.
19.
ChaoMV (2003) Neurotrophins and their receptors: A convergence point for many signalling pathways. Nat Rev Neurosci4: 299–309. DOI: 10.1038/nrn1078.
20.
ClarkeJRRossatoJIMonteiroS, et al. (2008) Posttraining activation of CB1 cannabinoid receptors in the CA1 region of the dorsal hippocampus impairs object recognition long-term memory. Neurobiol Learn Mem90: 374–381. DOI: 10.1016/j.nlm.2008.04.009.
21.
CochranSMKennedyMMcKercharCE, et al. (2003) Induction of metabolic hypofunction and neurochemical deficits after chronic intermittent exposure to phencyclidine: Differential modulation by antipsychotic drugs. Neuropsychopharmacology28: 265–275. DOI: 10.1038/sj.npp.1300031.
22.
CohenSJStackmanRWJr (2015) Assessing rodent hippocampal involvement in the novel object recognition task. A review. Behav Brain Res285: 105–117. DOI: 10.1016/j.bbr.2014.08.002.
23.
DauvermannMRLeeGDawsonN (2017) Glutamatergic regulation of cognition and functional brain connectivity: Insights from pharmacological, genetic and translational schizophrenia research. Br J Pharmacol174: 3136–3160. DOI: 10.1111/bph.13919.
24.
DawsonNThompsonRJMcVieA, et al. (2012) Modafinil reverses phencyclidine-induced deficits in cognitive flexibility, cerebral metabolism, and functional brain connectivity. Schizophr Bull38: 457–474. DOI: 10.1093/schbul/sbq090.
25.
DawsonNXiaoXMcDonaldM, et al. (2014) Sustained NMDA receptor hypofunction induces compromised neural systems integration and schizophrenia-like alterations in functional brain networks. Cereb Cortex24: 452–464. DOI: 10.1093/cercor/bhs322.
26.
de BartolomeisABuonaguroEFLatteG, et al. (2017) Immediate-early genes modulation by antipsychotics: Translational implications for a putative gateway to drug-induced long-term brain changes. Front Behav Neurosci11: 240. DOI: 10.3389/fnbeh.2017.00240.
27.
de BruinJPCSa`nchez-SantedFHeinsbroekRPW, et al. (1994) A behavioural analysis of rats with damage to the medial prefrontal cortex using the morris water maze: Evidence for behavioural flexibility, but not for impaired spatial navigation. Brain Res652: 323–333. DOI: 10.1016/0006-8993(94)90243-7.
28.
DeVitoLMEichenbaumH (2010) Distinct contributions of the hippocampus and medial prefrontal cortex to the ‘what-where-when’ components of episodic-like memory in mice. Behav Brain Res215: 318–325. DOI: 10.1016/j.bbr.2009.09.014.
29.
DiógenesMJCostenlaARLopesLV, et al. (2011) Enhancement of LTP in aged rats is dependent on endogenous BDNF. Neuropsychopharmacology36: 1823–1836. DOI: 10.1038/npp.2011.64.
30.
DoostdarNKimEGraysonB, et al. (2019) Global brain volume reductions in a sub-chronic phencyclidine animal model for schizophrenia and their relationship to recognition memory. J Psychopharmacol33: 1274–1287. DOI: 10.1177/0269881119844196.
31.
DorseySGRennCLCarim-ToddL, et al. (2006) In vivo restoration of physiological levels of truncated TrkB.T1 receptor rescues neuronal cell death in a trisomic mouse model. Neuron51: 21–28. DOI: 10.1016/j.neuron.2006.06.009.
32.
DuranyNMichelTZöchlingR, et al. (2001) Brain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses. Schizophr Res52: 79–86. DOI: 10.1016/s0920-9964(00)00084-0.
33.
EganMFKojimaMCallicottJH, et al. (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell112: 257–269. DOI: 10.1016/s0092-8674(03)00035-7.
34.
EgertonAReidLMcGregorS, et al. (2008) Subchronic and chronic PCP treatment produces temporally distinct deficits in attentional set shifting and prepulse inhibition in rats. Psychopharmacology198: 37–49. DOI: 10.1007/s00213-008-1071-5.
35.
EideFFViningEREideBL, et al. (1996) Naturally occurring truncated trkB receptors have dominant inhibitory effects on brain-derived neurotrophic factor signaling. J Neurosci16: 3123–3129.
36.
FaatehiMBasiriMNezhadiA, et al. (2019) Early enriched environment prevents cognitive impairment in an animal model of schizophrenia induced by MK-801: Role of hippocampal BDNF. Brain Res1711: 115–119. DOI: 10.1016/j.brainres.2019.01.023.
37.
FénelonKMukaiJXuB, et al. (2011) Deficiency of Dgcr8, a gene disrupted by the 22q11.2 microdeletion, results in altered short-term plasticity in the prefrontal cortex. Proc Natl Acad Sci U S A108: 4447–4452. DOI: 10.1073/pnas.1101219108.
38.
FigurovAPozzo-MillerLDOlafssonP, et al. (1996) Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus. Nature381: 706–709. DOI: 10.1038/381706a0.
39.
FioreMGraceAAKorfJ, et al. (2004) Impaired brain development in the rat following prenatal exposure to methylazoxymethanol acetate at gestational day 17 and neurotrophin distribution. Neuroreport15: 1791–1795. DOI: 10.1097/01.wnr.0000135934.03635.6a.
40.
FontinhaBMDiógenesMJRibeiroJA, et al. (2008) Enhancement of long-term potentiation by brain-derived neurotrophic factor requires adenosine A2A receptor activation by endogenous adenosine. Neuropharmacology54: 924–933. DOI: 10.1016/j.neuropharm.2008.01.011.
41.
FujitaYIshimaTKunitachiS, et al. (2008) Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of the antibiotic drug minocycline. Prog Neuropsychopharmacol Biol Psychiatry32: 336–339. DOI: 10.1016/j.pnpbp.2007.08.031.
42.
FumagalliFRacagniGRivaMA (2006) Shedding light into the role of BDNF in the pharmacotherapy of Parkinson’s disease. Pharmacogenomics J6: 95–104. DOI: 10.1038/sj.tpj.6500360.
43.
Fusar-PoliPPapanastasiouEStahlD, et al. (2015) Treatments of negative symptoms in schizophrenia: Meta-analysis of 168 randomized placebo-controlled trials. Schizophr Bull41: 892–899. DOI: 10.1093/schbul/sbu170.
44.
GaskinPLAlexanderSPFoneKC (2014) Neonatal phencyclidine administration and post-weaning social isolation as a dual-hit model of ‘schizophrenia-like’ behaviour in the rat. Psychopharmacology231: 2533–2545. DOI: 10.1007/s00213-013-3424-y.
45.
GemperleAYEnzAPozzaMF, et al. (2003) Effects of clozapine, haloperidol and iloperidone on neurotransmission and synaptic plasticity in prefrontal cortex and their accumulation in brain tissue: An in vitro study. Neuroscience117: 681–695. DOI: 10.1016/s0306-4522(02)00769-8.
GraysonBIdrisNNeillJ (2007) Atypical antipsychotics attenuate a sub-chronic PCP-induced cognitive deficit in the novel object recognition task in the rat. Behav Brain Res184: 31–38. DOI: 10.1016/j.bbr.2007.06.012.
48.
HarteMKCahirMReynoldsGP, et al. (2007) Sub-chronic phencyclidine administration increases brain-derived neurotrophic factor in the RAT hippocampus. Schizophr Res94: 371–372. DOI: 10.1016/j.schres.2007.04.032.
49.
HashimotoKFujitaYIyoM (2007) Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of fluvoxamine: Role of sigma-1 receptors. Neuropsychopharmacology32: 514–521. DOI: 10.1038/sj.npp.1301047.
50.
HashimotoKFujitaYShimizuE, et al. (2005) Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of clozapine, but not haloperidol. Eur J Pharmacol519: 114–117. DOI: 10.1016/j.ejphar.2005.07.002.
51.
HashimotoKIshimaTFujitaY, et al. (2008) Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of the novel selective α7 nicotinic receptor agonist SSR180711. Biol Psychiatry63: 92–97. DOI: 10.1016/j.biopsych.2007.04.034.
52.
HempelCMHartmanKHWangXJ, et al. (2000) Multiple forms of short-term plasticity at excitatory synapses in rat medial prefrontal cortex. J Neurophysiol83: 3031–3041. DOI: 10.1152/jn.2000.83.5.3031.
53.
HoriTAbeSBabaA, et al. (2000) Effects of repeated phencyclidine treatment on serotonin transporter in rat brain. Neurosci Lett280: 53–56. DOI: 10.1016/s0304-3940(99)00991-x.
54.
HoriguchiMMeltzerHY (2013) Blonanserin reverses the phencyclidine (PCP)-induced impairment in novel object recognition (NOR) in rats: Role of indirect 5-HT(1A) partial agonism. Behav Brain Res247: 158–164. DOI: 10.1016/j.bbr.2013.03.027.
55.
HughesRN (2004) The value of spontaneous alternation behavior (SAB) as a test of retention in pharmacological investigations of memory. Neurosci Biobehav Rev28: 497–505. DOI: 10.1016/j.neubiorev.2004.06.006.
56.
HuhnMNikolakopoulouASchneider-ThomaJ, et al. (2019) Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: A systematic review and network meta-analysis. Lancet394: 939–951. DOI: 10.1016/S0140-6736(19)31135-3.
57.
IritaniSNiizatoKNawaH, et al. (2003) Immunohistochemical study of brain-derived neurotrophic factor and its receptor, TrkB, in the hippocampal formation of schizophrenic brains. Prog Neuropsychopharmacol Biol Psychiatry27: 801–807. DOI: 10.1016/S0278-5846(03)00112-X.
58.
JentschJ (1997) Subchronic phencyclidine administration reduces mesoprefrontal dopamine utilization and impairs prefrontal cortical-dependent cognition in the rat. Neuropsychopharmacology17: 92–99. DOI: 10.1016/S0893-133X(97)00034-1.
KalinichevMRobbinsMJHartfieldEM, et al. (2008) Comparison between intraperitoneal and subcutaneous phencyclidine administration in Sprague-Dawley rats: A locomotor activity and gene induction study. Prog Neuropsychopharmacol Biol Psychiatry32: 414–422. DOI: 10.1016/j.pnpbp.2007.09.008.
61.
KapurSSeemanP (2002) NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D(2) and serotonin 5-HT(2)receptors-implications for models of schizophrenia. Mol Psychiatry7: 837–844. DOI: 10.1038/sj.mp.4001093.
62.
KerkhofsACanasPMTimmermanAJ, et al. (2018) Adenosine A2A receptors control glutamatergic synaptic plasticity in fast spiking interneurons of the prefrontal cortex. Front Pharmacol9: 133. DOI: 10.3389/fphar.2018.00133.
63.
KorteMCarrollPWolfE, et al. (1995) Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proc Natl Acad Sci U S A92: 8856–8860. DOI: 10.1073/pnas.92.19.8856.
64.
KraeuterA-KGuestPCSarnyaiZ (2019) The Y-Maze for Assessment of Spatial Working and Reference Memory in Mice. Methods Mol Biol1916: 105–111. DOI: 10.1007/978-1-4939-8994-2_10.
65.
KrauseMZhuYHuhnM, et al. (2018) Antipsychotic drugs for patients with schizophrenia and predominant or prominent negative symptoms: A systematic review and meta-analysis. Eur Arch Psychiatry Clin Neurosci268: 625–639. DOI: 10.1007/s00406-018-0869-3.
66.
LalondeR (2002) The neurobiological basis of spontaneous alternation. Neurosci Biobehav Rev26: 91–104. DOI: 10.1016/s0149-7634(01)00041-0.
67.
LeeFSKimAHKhursigaraG, et al. (2001) The uniqueness of being a neurotrophin receptor. Curr Opin Neurobiol11: 281–286. DOI: 10.1016/s0959-4388(00)00209-9.
68.
LeeGZhouY (2019) NMDAR Hypofunction Animal Models of Schizophrenia. Front Mol Neurosci12: 185. DOI: 10.3389/fnmol.2019.00185.
69.
LeePRBradyDLShapiroRA, et al. (2005) Social interaction deficits caused by chronic phencyclidine administration are reversed by oxytocin. Neuropsychopharmacology30. DOI: 10.1038/sj.npp.1300722.
70.
LegerMNeillJC (2016) A systematic review comparing sex differences in cognitive function in schizophrenia and in rodent models for schizophrenia, implications for improved therapeutic strategies. Neurosci Biobehav Rev68: 979–1000. DOI: 10.1016/j.neubiorev.2016.06.029.
71.
LeshTANiendamTAMinzenbergMJ, et al. (2011) Cognitive control deficits in schizophrenia: Mechanisms and meaning. Neuropsychopharmacology36: 316–338. DOI: 10.1038/npp.2010.156.
72.
LiRMaXWangG, et al. (2016) Why sex differences in schizophrenia?J Transl Neurosci1: 37–42.
73.
LiangKCHonWTyanYM, et al. (1994) Involvement of hippocampal NMDA and AMPA receptors in acquisition, formation and retrieval of spatial memory in the Morris water maze. Chinese J Physiol37: 201–212.
74.
LindahlJSKeiferJ (2004) Glutamate receptor subunits are altered in forebrain and cerebellum in rats chronically exposed to the NMDA receptor antagonist phencyclidine. Neuropsychopharmacology29: 2065–2073. DOI: 10.1038/sj.npp.1300485.
75.
McLeanSLHarteMKNeillJC, et al. (2017) Dopamine dysregulation in the prefrontal cortex relates to cognitive deficits in the sub-chronic PCP-model for schizophrenia: A preliminary investigation. J Psychopharmacology31: 660–666. DOI: 10.1177/0269881117704988.
76.
MarderSRCannonTD (2019) Schizophrenia. N Engl J Med381: 1753–1761. DOI: 10.1056/NEJMra1808803.
77.
MarquisJ-PAudetM-CDoréFY, et al. (2007) Delayed alternation performance following subchronic phencyclidine administration in rats depends on task parameters. Prog Neuropsychopharmacol Biol Psychiatry31: 1108–1112. DOI: 10.1016/j.pnpbp.2007.03.017.
78.
MartinezZAEllisonGDGeyerMA, et al. (1999) Effects of sustained phencyclidine exposure on sensorimotor gating of startle in rats. Neuropsychopharmacology21: 28–39. DOI: 10.1016/S0893-133X(98)00137-7.
79.
MeunierCNJChameauPFossierPM (2017) Modulation of synaptic plasticity in the cortex needs to understand all the players. Front Synaptic Neurosci9: 2. DOI: 10.3389/fnsyn.2017.00002.
80.
MinichielloLCalellaAMMedinaDL, et al. (2002) Mechanism of TrkB-mediated hippocampal long-term potentiation. Neuron36: 121–137. DOI: 10.1016/s0896-6273(02)00942-x.
81.
MitsadaliIGraysonBIdrisNF, et al. (2020) Aerobic exercise improves memory and prevents cognitive deficits of relevance to schizophrenia in an animal model. J Psychopharmacology34: 695–708. DOI: 10.1177/0269881120922963.
82.
MorrisRGMGarrudPRawlinsJNP, et al. (1982) Place navigation impaired in rats with hippocampal lesions. Nature297: 681–683. DOI: 10.1038/297681a0.
83.
MouriAKosekiTNarusawaS, et al. (2012) Mouse strain differences in phencyclidine-induced behavioural changes. Int J Neuropsychopharmacol15: 767–779. DOI: 10.1017/S146114571100085X.
84.
MouroFMRibeiroJASebastiãoAM, et al. (2018) Chronic, intermittent treatment with a cannabinoid receptor agonist impairs recognition memory and brain network functional connectivity. J Neurochem147: 71–83. DOI: 10.1111/jnc.14549.
85.
NabeshimaTFukayaHYamaguchiK, et al. (1987) Development of tolerance and supersensitivity to phencyclidine in rats after repeated administration of phencyclidine. Eur J Pharmacol135: 23–33. DOI: 10.1016/0014-2999(87)90753-9.
86.
Nakatani-PawlakAYamaguchiKTatsumiY, et al. (2009) Neonatal phencyclidine treatment in mice induces behavioral, histological and neurochemical abnormalities in adulthood. Biol Pharm Bull32: 1576–1583. DOI: 10.1248/bpb.32.1576.
87.
NeillJCGraysonBKissB, et al. (2016) Effects of cariprazine, a novel antipsychotic, on cognitive deficit and negative symptoms in a rodent model of schizophrenia symptomatology. Eur Neuropsychopharmacol26: 3–14. DOI: 10.1016/j.euroneuro.2015.11.016.
88.
NeillJCHarteMKHaddadPM, et al. (2014) Acute and chronic effects of NMDA receptor antagonists in rodents, relevance to negative symptoms of schizophrenia: A translational link to humans. Eur Neuropsychopharmacol24: 822–835. DOI: 10.1016/j.euroneuro.2013.09.011.
89.
NicollRAMalenkaRC (1999) Expression mechanisms underlying NMDA receptor-dependent long-term potentiation. Ann N Y Acad Sci868: 515–525. DOI: 10.1111/j.1749-6632.1999.tb11320.x.
90.
NietoRKukuljanMSilvaH (2013) BDNF and schizophrenia: From neurodevelopment to neuronal plasticity, learning, and memory. Front Psychiatry4: 45. DOI: 10.3389/fpsyt.2013.00045.
91.
NomuraTOyamadaYFernandesHB, et al. (2016) Subchronic phencyclidine treatment in adult mice increases GABAergic transmission and LTP threshold in the hippocampus. Neuropharmacology100: 90–97. DOI: 10.1016/j.neuropharm.2015.04.012.
92.
PalominoAVallejo-IllarramendiAGonzález-PintoA, et al. (2006) Decreased levels of plasma BDNF in first-episode schizophrenia and bipolar disorder patients. Schizophr Res86: 321–322. DOI: 10.1016/j.schres.2006.05.028.
93.
ParkSWPhuongVTLeeCH, et al. (2011) Effects of antipsychotic drugs on BDNF, GSK-3β, and β-catenin expression in rats subjected to immobilization stress. Neurosci Res71: 335–340. DOI: 10.1016/j.neures.2011.08.010.
94.
PengSLiWLvL, et al. (2018) BDNF as a biomarker in diagnosis and evaluation of treatment for schizophrenia and depression. Discov Med26: 127–136.
95.
PillaiAMahadikSP (2008) Increased truncated TrkB receptor expression and decreased BDNF/TrkB signaling in the frontal cortex of reeler mouse model of schizophrenia. Schizophr Res100: 325–333. DOI: 10.1016/j.schres.2007.11.030.
96.
PorcherCMedinaIGaiarsaJ-L (2018) Mechanism of BDNF modulation in GABAergic synaptic transmission in healthy and disease brains. Front Cell Neurosci12: 273. DOI: 10.3389/fncel.2018.00273.
97.
PrattJWinchesterCDawsonN, et al. (2012) Advancing schizophrenia drug discovery: Optimizing rodent models to bridge the translational gap. Nat Rev Drug Discov11: 560–579. DOI: 10.1038/nrd3649.
98.
RedrobeJPBullSPlathN (2010) Translational aspects of the novel object recognition task in rats abstinent following sub-chronic treatment with phencyclidine (PCP): Effects of modafinil and relevance to cognitive deficits in schizophrenia. Front Psychiatry1: 146. DOI: 10.3389/fpsyt.2010.00146.
99.
SantiniMARatnerCAznarS, et al. (2013) Enhanced prefrontal serotonin 2A receptor signaling in the subchronic phencyclidine mouse model of schizophrenia. J Neurosci Res91: 634–641. DOI: 10.1002/jnr.23198.
100.
SeemanPKoFTallericoT (2005) Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics. Mol Psychiatry10: 877–883. DOI: 10.1038/sj.mp.4001682.
101.
SembaJWakutaMSuharaT (2006) Different effects of chronic phencyclidine on brain-derived neurotrophic factor in neonatal and adult rat brains. Addict Biol11: 126–130. DOI: 10.1111/j.1369-1600.2006.00023.x.
102.
ShanLLiuTZhangZ, et al. (2018) Schizophrenia-like olfactory dysfunction induced by acute and postnatal phencyclidine exposure in rats. Schizophr Res199: 274–280. DOI: 10.1016/j.schres.2018.02.045.
103.
SigurdssonTDuvarciS (2015) Hippocampal-prefrontal interactions in cognition, behavior and psychiatric disease. Front Syst Neurosci9: 190. DOI: 10.3389/fnsys.2015.00190.
104.
SnigdhaSHoriguchiMHuangM, et al. (2010) Attenuation of phencyclidine-induced object recognition deficits by the combination of atypical antipsychotic drugs and pimavanserin (ACP 103), a 5-hydroxytryptamine(2A) receptor inverse agonist. J Pharmacol Exp Ther332: 622–631. DOI: 10.1124/jpet.109.156349.
105.
SnigdhaSNeillJC (2008) Efficacy of antipsychotics to reverse phencyclidine-induced social interaction deficits in female rats–a preliminary investigation. Behav Brain Res187: 489–494. DOI: 10.1016/j.bbr.2007.10.012.
106.
SnigdhaSNeillJCMcLeanSL, et al. (2011) Phencyclidine (PCP)-induced disruption in cognitive performance is gender-specific and associated with a reduction in brain-derived neurotrophic factor (BDNF) in specific regions of the female rat brain. J Mol Neurosci43: 337–345. DOI: 10.1007/s12031-010-9447-5.
107.
SutcliffeJSMarshallKMNeillJC (2007) Influence of gender on working and spatial memory in the novel object recognition task in the rat. Behav Brain Res177: 117–125. DOI: 10.1016/j.bbr.2006.10.029.
108.
TakahashiMShirakawaOToyookaK, et al. (2000) Abnormal expression of brain-derived neurotrophic factor and its receptor in the corticolimbic system of schizophrenic patients. Mol Psychiatry5: 293–300. DOI: 10.1038/sj.mp.4000718.
109.
TanibuchiYFujitaYKohnoM, et al. (2009) Effects of quetiapine on phencyclidine-induced cognitive deficits in mice: A possible role of α1-adrenoceptors. Eur Neuropsychopharmacol19: 861–867. DOI: 10.1016/j.euroneuro.2009.07.005.
110.
TanqueiroSRRamalhoRMRodriguesTM, et al. (2018) Inhibition of NMDA receptors prevents the loss of BDNF function induced by amyloid β. Front Pharmacol9: 237. DOI: 10.3389/fphar.2018.00237.
111.
Thompson RayM (2011) Decreased BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders. J Psychiatry Neurosci36: 195–203. DOI: 10.1503/jpn.100048.
112.
VickeryRMMorrisSHBindmanLJ (1997) Metabotropic Glutamate Receptors Are Involved in Long-Term Potentiation in Isolated Slices of Rat Medial Frontal Cortex. J Neurophysiol78: 3039–3046. DOI: 10.1152/jn.1997.78.6.3039.
113.
WeickertCSLigonsDLRomanczykT, et al. (2005) Reductions in neurotrophin receptor mRNAs in the prefrontal cortex of patients with schizophrenia. Mol Psychiatry10: 637–650. DOI: 10.1038/sj.mp.4001678.
114.
WongJRothmondDAWebsterMJ, et al. (2013) Increases in Two Truncated TrkB Isoforms in the Prefrontal Cortex of People With Schizophrenia. Schizophr Bull39: 130–140. DOI: 10.1093/schbul/sbr070.
115.
YamazakiMYamamotoNYarimizuJ, et al. (2018) Functional mechanism of ASP5736, a selective serotonin 5-HT5A receptor antagonist with potential utility for the treatment of cognitive dysfunction in schizophrenia. Eur Neuropsychopharmacol28: 620–629. DOI: 10.1016/j.euroneuro.2018.03.003.
116.
YuWZhuMFangH, et al. (2019) Risperidone Reverses the Downregulation of BDNF in Hippocampal Neurons and MK801-Induced Cognitive Impairment in Rats. Front Behav Neurosci13: 163. DOI: 10.3389/fnbeh.2019.00163.
117.
ZainMARouhollahiEPandyV, et al. (2018) Phencyclidine dose optimisation for induction of spatial learning and memory deficits related to schizophrenia in C57BL/6 mice. Exp Anim67: 421–429. DOI: 10.1538/expanim.18-0006.
118.
ZhaoM-GToyodaHLeeY-S, et al. (2005) Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory. Neuron47: 859–872. DOI: 10.1016/j.neuron.2005.08.014.
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