Abstract
Rational
Prepulse inhibition (PPI) is suppression of the startle reflex by a weaker sensory stimulus (prepulse) preceding the startling stimulus. In people with schizophrenia, impairment of attentional modulation of PPI, but not impairment of baseline PPI, is correlated with symptom severity. In rats, both fear conditioning of prepulse and perceptually spatial separation between the conditioned prepulse and a noise masker enhance PPI (the paradigms of attentional modulation of PPI).
Objectives
As a neurodevelopmental model of schizophrenia, isolation rearing impairs both baseline PPI and attentional modulations of PPI in rats. This study examined in Sprague-Dawley male rats whether neonatally blocking N-methyl-d-aspartate (NMDA) receptors specifically affects attentional modulations of PPI during adulthood.
Results
Both socially reared rats with neonatal exposure to the NMDA receptor antagonist MK-801 and isolation-reared rats exhibited augmented startle responses, but only isolation rearing impaired baseline PPI. Fear conditioning of the prepulse enhanced PPI in socially reared rats, but MK-801-treated rats lost the prepulse feature specificity. Perceptually spatial separation between the conditioned prepulse and a noise masker further enhanced PPI only in normally reared rats. Clozapine administration during adulthood generally weakened startle, enhanced baseline PPI in neonatally interrupted rats, and restored the fear conditioning-induced PPI enhancement in isolation-reared rats with a loss of the prepulse feature specificity. Clozapine administration also abolished both the perceptual separation-induced PPI enhancement in normally reared rats and the fear conditioning-induced PPI enhancement in MK-801-treated rats.
Conclusions
Isolation rearing impairs both baseline PPI and attentional modulations of PPI, but neonatally disrupting NMDA receptor-mediated transmissions specifically impair attentional modulations of PPI. Clozapine has limited alleviating effects.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abekawa T, Ito K, Nakagawa S, Koyama T (2007) Prenatal exposure to an NMDA receptor antagonist, MK-801 reduces density of parvalbumin-immunoreactive GABAergic neurons in the medial prefrontal cortex and enhances phencyclidine-induced hyperlocomotion but not behavioral sensitization to methamphetamine in postpubertal rats. Psychopathology 192:303–316. doi:10.1007/s00213-007-0729-8
Amitai N, Semenova S, Markou A (2007) Cognitive-disruptive effects of the psychotomimetic phencyclidine and attenuation by atypical antipsychotic medications in rats. Psychopathology 193:521–537. doi:10.1007/s00213-007-0808-x
Andersen RA, Cui H (2009) Intention, action planning, and decision making in parietal-frontal circuits. Neuron 63:568–583. doi:10.1016/j.neuron.2009.08.028
Arndt DL, Johns KC, Dietz ZK, Cain ME (2015) Environmental condition alters amphetamine self-administration: role of the mGluR5 receptor and schedule of reinforcement. Psychopathology 232:3741–3752. doi:10.1007/s00213-015-4031-x
Auclair AL, Besnard J, Newman-Tancredi A, Depoortère R (2009) The five choice serial reaction time task: comparison between Sprague–Dawley and Long-Evans rats on acquisition of task, and sensitivity to phencyclidine. Pharmacol Biochem Behav 92:363–369. doi:10.1016/j.pbb.2009.01.005
Ayala JE, Chen Y, Banko JL, Sheffler DJ, Williams R, Telk AN et al (2009) mGluR5 positive allosteric modulators facilitate both hippocampal LTP and LTD and enhance spatial learning. Neuropsychopharmacology 34:2057–2071. doi:10.1038/npp.2009.30
Bergado-Acosta JR, Sangha S, Narayanan RT, Obata K, Pape HC, Stork O (2008) Critical role of the 65-kDa isoform of glutamic acid decarboxylase in consolidation and generalization of Pavlovian fear memory. Learn Mem 15:163–171. doi:10.1101/lm.705408
Beninger RJ, Jhamandas A, Aujla H, Xue I, Dagnone RV, Boegman RJ et al (2002) Neonatal exposure to the glutamate receptor antagonist MK-801: effects on locomotor activity and pre-pulse inhibition before and after sexual maturity in rats. Neurotox Res 4:477–488. doi:10.1080/10298420290031414
Bordi F, LeDoux J (1992) Sensory tuning beyond the sensory system: an initial analysis of auditory response properties of neurons in the lateral amygdaloid nucleus and overlying areas of the striatum. J Neurosci 12:2493–2503
Bourdelais AJ, Deutch AY (1994) The effects of haloperidol and clozapine on extracellular GABA levels in the prefrontal cortex of the rat: an in vivo microdialysis study. Cereb Cortex 4:69–77. doi:10.1093/cercor/4.1.69
Broberg BV, Dias R, Glenthøj BY, Olsen CK (2008) Evaluation of a neurodevelopmental model of schizophrenia-early postnatal PCP treatment in attentional set-shifting. Behav Brain Res 190:160–163. doi:10.1016/j.bbr.2008.02.020
Broberg BV, Glenthøj BY, Dias R, Larsen DB, Olsen CK (2009) Reversal of cognitive deficits by an ampakine (CX516) and sertindole in two animal models of schizophrenia-sub-chronic and early postnatal PCP treatment in attentional set-shifting. Psychopathology 206:631–640. doi:10.1007/s00213-009-1540-5
Buuse M, Garner B, Koch M (2003) Neurodevelopmental animal models of schizophrenia: effects on prepulse inhibition. Curr Mol Med 3:459–471. doi:10.2174/1566524033479627
Dalmaso M, Galfano G, Tarqui L, Forti B, Castelli L (2013) Is social attention impaired in schizophrenia? Gaze, but not pointing gestures, is associated with spatial attention deficits. Neuropsychology 27:608–613. doi:10.1037/a0033518
Du Y, Li J, Wu X, Li L (2009) Precedence-effect-induced enhancement of prepulse inhibition in socially reared but not isolation-reared rats. Cogn Affect Behav Neurosci 9:44–58. doi:10.3758/CABN.9.1.44
Du Y, Wu X, Li L (2010) Emotional learning enhances stimulus-specific top-down modulation of sensorimotor gating in socially reared rats but not isolation-reared rats. Behav Brain Res 206:192–201. doi:10.1016/j.bbr.2009.09.012
Du Y, Wu X, Li L (2011) Differentially organized top-down modulation of prepulse inhibition of startle. J Neurosci 31:13644–13653. doi:10.1523/JNEUROSCI.1292-11.2011
Du Y, Wang Q, Zhang Y, Wu XH, Li L (2012) Perceived target-masker separation unmasks responses of lateral amygdala to the emotionally conditioned target sounds in awake rats. Neuroscience 225:249–257. doi:10.1016/j.neuroscience.2012.08.022
Farnbach-Pralong D, Bradbury R, Copolov D, Dean B (1998) Clozapine and olanzapine treatment decreases rat cortical and limbic GABA(A) receptors. Eur J Pharmacol 349:7–8
Fendt M, Li L, Yeomans JS (2001) Brainstem circuits mediating prepulse inhibition of the startle reflex. Psychopathology 156:216–224. doi:10.1007/s002130100794
Fowler SW, Walker JM, Klakotskaia D, Will MJ, Serfozo P, Simonyi A et al (2013) Effects of a metabotropic glutamate receptor 5 positive allosteric modulator, CDPPB, on spatial learning task performance in rodents. Neurobiol Learn Mem 99:25–31. doi:10.1016/j.nlm.2012.10.010
Freyman RL, Helfer KS, McCall DD, Clifton RK (1999) The role of perceived spatial separation in the unmasking of speech. J Acoust Soc Am 106:3578–3588. doi:10.1121/1.428211
Frogley C, Taylor D, Dickens G, Picchioni M (2012) A systematic review of the evidence of clozapine’s anti-aggressive effects. Int J Neuropsychopharmacol 15:1351–1371. doi:10.1017/S146114571100201X
Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR (2001) Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopathology 156:117–154. doi:10.1007/s002130100811
Gilland E, Bona E, Levene M, Hagberg H (1997) Magnesium and the N-methyl-D-aspartate receptor antagonist dizocilpine maleate neither increase glucose use nor induce a 72-kilodalton heat shock protein expression in the immature rat brain. Pediatr Res 42:472–477. doi:10.1203/00006450-199710000-00008
Hansen HH, Briem T, Dzietko M, Sifringer M, Voss A, Rzeski W et al (2004) Mechanisms leading to disseminated apoptosis following NMDA receptor blockade in the developing rat brain. Neurobiol Dis 16:440–453. doi:10.1016/j.nbd.2004.03.013
Hazlett EA, Romero MJ, Haznedar MM, New AS, Goldstein KE, Newmark RE et al (2007) Deficient attentional modulation of startle eyeblink is associated with symptom severity in the schizophrenia spectrum. Schizophr Res 93:288–295. doi:10.1016/j.schres.2007.03.012
Heidbreder CA, Foxton R, Cilia J, Hughes ZA, Shah AJ, Atkins A, Hunter JA et al (2001) Increased responsiveness of dopamine to atypical, but not typical antipsychotics in the medial prefrontal cortex of rats reared in isolation. Psychopathology 156:338–351. doi:10.1007/s002130100760
Houthoofd SA, Morrens M, Sabbe BG (2008) Cognitive and psychomotor effects of risperidone in schizophrenia and schizoaffective disorder. Clin Ther 30:1565–1589. doi:10.1016/j.clinthera.2008.09.014
Huang EJ, Reichardt LF (2003) Trk receptors: roles in neuronal signal transduction. Annu Rev Biochem 72:609–642
Huang J, Wu X, Yeomans J, Li L (2005) Opposite effects of tetanic stimulation of the auditory thalamus or auditory cortex on the acoustic startle reflex in awake rats. Eur J Neurosci 21:1943–1956. doi:10.1111/j.1460-9568.2005.04030.x
Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vöckler J, Dikranian K et al (1999) Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 283:70–74. doi:10.1126/science.283.5398.70
Ison JR, Hammond GR (1971) Modification of the startle reflex in rat by changes in the auditory and visual environments. J Comp Physiol Psychol 75:452. doi:10.1037/h0030934
Jantas D, Lason W (2009) Different mechanisms of NMDA-mediated protection against neuronal apoptosis: a stimuli-dependent effect. Neurochem Res 34:2040–2054. doi:10.1007/s11064-009-9991-y
Jia Z, Lu Y, Henderson J, Taverna F, Romano C, Abramow-Newerly W et al (1998) Selective abolition of the NMDA component of long-term potentiation in mice lacking mGluR5. Learn Mem 5:331–343. doi:10.1101/lm.5.4.331
Kang H, Schuman EM (1995) Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus. Science 267:1658–1662. doi:10.1126/science.7886457
Kanungo AK, Liadis N, Robertson J, Woo M, Henderson JT (2009) Excitatory tonus is required for the survival of granule cell precursors during postnatal development within the cerebellum. Neuroscience 158:1364–1377. doi:10.1016/j.neuroscience.2008.10.062
Kaplan DR, Miller FD (2000) Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol 10:381–391. doi:10.1016/S0959-4388(00)00092-1
Karkhanis AN, Alexander NJ, McCool BA, Weiner JL, Jones SR (2015) Chronic social isolation during adolescence augments catecholamine response to acute ethanol in the basolateral amygdala. Synapse 69:385–395. doi:10.1002/syn.21826
Kelly JB, Masterton B (1977) Auditory sensitivity of the albino rat. J Comp Physiol Psychol 91:930–936
Kelly JB, Sally SL (1988) Organization of auditory cortex in the albino rat: binaural response properties. J Neurophysiol 59:1756–1769
Koike H, Ibi D, Mizoguchi H, Nagai T, Nitta A, Takuma K et al (2009) Behavioral abnormality and pharmacologic response in social isolation-reared mice. Behav Brain Res 202:114–121. doi:10.1016/j.bbr.2009.03.028
Komuro H, Rakic P (1993) Modulation of neuronal migration by NMDA receptors. Science 260:95–97. doi:10.1126/science.8096653
Le Pen G, Moreau JL (2002) Disruption of prepulse inhibition of startle reflex in a neurodevelopmental model of schizophrenia: reversal by clozapine, olanzapine and risperidone but not by haloperidol. Neuropsychopharmacology 27:1–11. doi:10.1016/S0893-133X(01)00383-9
Le Pen G, Grottick AJ, Higgins GA, Moreau JL (2003) Phencyclidine exacerbates attentional deficits in a neurodevelopmental rat model of schizophrenia. Neuropsychopharmacology 28:1799–1809. doi:10.1038/sj.npp.1300208
Lei M, Luo L, Qu T, Jia H, Li L (2014) Perceived location specificity in perceptual separation-induced but not fear conditioning-induced enhancement of prepulse inhibition in rats. Behav Brain Res 269:87–94. doi:10.1016/j.bbr.2014.04.030
Leng A, Feldon J, Ferger B (2004) Long-term social isolation and medial prefrontal cortex: dopaminergic and cholinergic neurotransmission. Pharmacol Biochem Behav 77:371–379. doi:10.1016/j.pbb.2003.11.011
Li JT, Zhao YY, Wang HL, Wang XD, Su YA, Si TM (2015) Long-term effects of neonatal exposure to MK-801 on recognition memory and excitatory-inhibitory balance in rat hippocampus. Neuroscience 308:134–143. doi:10.1016/j.neuroscience.2015.09.003
Li L, Frost BJ (2000) Azimuthal directional sensitivity of prepulse inhibition of the pinna startle reflex in decerebrate rats. Brain Res Bull 51:95–100. doi:10.1016/S0361-9230(99)00215-4
Li L, Shao J (1998) Restricted lesions to ventral prefrontal subareas block reversal learning but not visual discrimination learning in rats. Physiol Behav 65:371–379. doi:10.1016/S0031-9384(98)00216-9
Li L, Daneman M, Qi GQ, Schneider BA (2004) Does the information content of an irrelevant source differentially affect speech recognition in younger and older adults? J Exp Psychol Hum Percept Perform 30:1077–1091. doi:10.1037/0096-1523.30.6.1077
Li L, Qi JG, He Y, Alain C, Schneider BA (2005) Attribute capture in the precedence effect for long-duration noise sounds. Hear Res 202:235–247. doi:10.1016/j.heares.2004.10.007
Li L, Du Y, Li N, Wu X, Wu Y (2009) Top-down modulation of prepulse inhibition of the startle reflex in humans and rats. Neurosci Biobehav Rev 33:1157–1167. doi:10.1016/j.neubiorev.2009.02.001
Li N, Wu X, Li L (2007) Chronic administration of clozapine alleviates reversal-learning impairment in isolation-reared rats. Behav Pharmacol 18:135–145. doi:10.1097/FBP.0b013e3280d3ee83
Lim AL, Taylor DA, Malone DT (2012a) Consequences of early life MK-801 administration: long-term behavioural effects and relevance to schizophrenia research. Behav Brain Res 227:276–286. doi:10.1016/j.bbr.2011.10.052
Lim AL, Taylor DA, Malone DT (2012b) A two-hit model: behavioural investigation of the effect of combined neonatal MK-801 administration and isolation rearing in the rat. J Psychopharmacol 26:1252–1264. doi:10.1177/0269881111430751
Litovsky RY, Colburn HS, Yost WA, Guzman SJ (1999) The precedence effect. J Acoust Soc Am 106:1633–1654. doi:10.1121/1.427914
Liu H, Ren Z, Zhong J, Cai H, Chen X, Li J (2014) Haloperidol and clozapine reverse MK-801-induced deficits in hypoactivity, but not the impairment of spatial memory in Sprague–Dawley rats. Int J Pharmacol 10:120–128. doi:10.3923/ijp.2014.120.128
Luz M, Mohr E, Fibiger HC (2016) GDNF-induced cerebellar toxicity: a brief review. Neurotoxicology 52:46–56. doi:10.1016/j.neuro.2015.10.011
Manning SM, Boll G, Fitzgerald E, Selip DB, Volpe JJ, Jensen FE (2011) The clinically available NMDA receptor antagonist, memantine, exhibits relative safety in the developing rat brain. Int J Dev Neurosci 29:767–773. doi:10.1016/j.ijdevneu.2011.05.005
McLean SL, Grayson B, Harris M, Protheroe C, Woolley ML, Neill JC (2010) Isolation rearing impairs novel object recognition and attentional set shifting performance in female rats. J Psychopharmacol 24:57–63. doi:10.1177/0269881108093842
Melendez RI, Gregory ML, Bardo MT, Kalivas PW (2004) Impoverished rearing environment alters metabotropic glutamate receptor expression and function in the prefrontal cortex. Neuropsychopharmacology 29:1980–1987. doi:10.1038/sj.npp.1300507
Meltzer HY, McGurk SR (1999) The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophr Bull 25:233–256. doi:10.1093/oxfordjournals.schbul.a033376
Möller M, Du Preez JL, Emsley R, Harvey BH (2011) Isolation rearing-induced deficits in sensorimotor gating and social interaction in rats are related to cortico-striatal oxidative stress, and reversed by sub-chronic clozapine administration. Eur Neuropsychopharmacol 21:471–483. doi:10.1016/j.euroneuro.2010.09.006
Möller M, Du Preez JL, Viljoen FP, Berk M, Emsley R, Harvey BH (2013) Social isolation rearing induces mitochondrial, immunological, neurochemical and behavioural deficits in rats, and is reversed by clozapine or N-acetyl cysteine. Brain Behav Immun 30:156–167. doi:10.1016/j.bbi.2012.12.011
Nozari M, Shabani M, Farhangi AM, Mazhari S, Atapour N (2015) Sex-specific restoration of MK-801-induced sensorimotor gating deficit by environmental enrichment. Neuroscience 299:28–34. doi:10.1016/j.neuroscience.2015.04.050
O’Connor WT, O’Shea SD (2015) Clozapine and GABA transmission in schizophrenia disease models: establishing principles to guide treatments. Pharmacol Ther 150:47–80. doi:10.1016/j.pharmthera.2015.01.005
Okada R, Matsumoto K, Tsushima R, Fujiwara H, Tsuneyama K (2014) Social isolation stress-induced fear memory deficit is mediated by down-regulated neuro-signaling system and Egr-1 expression in the brain. Neurochem Res 39:875–882. doi:10.1007/s11064-014-1283-5
Otoya RE, Seltzer AM, Donoso AO (1997) Acute and long-lasting effects of neonatal hypoxia on (+)-3-[125I]MK-801 binding to NMDA brain receptors. Exp Neurol 148:92–99. doi:10.1006/exnr.1997.6612
Palmer MJ, Irving AJ, Seabrook GR, Jane DE, Collingridge GL (1997) The group I mGlu receptor agonist DHPG induces a novel form of LTD in the CA1 region of the hippocampus. Neuropharmacology 36:1517–1532. doi:10.1016/S0028-3908(97)00181-0
Piantadosi PT, Floresco SB (2014) Prefrontal cortical GABA transmission modulates discrimination and latent inhibition of conditioned fear: relevance for schizophrenia. Neuropsychopharmacology 39:2473–2484. doi:10.1038/npp.2014.929
Reep RL, Chandler HC, King V, Corwin JV (1994) Rat posterior parietal cortex: topography of corticocortical and thalamic connections. Exp Brain Res 100:67–84. doi:10.1007/BF00227280
Romanski LM, LeDoux JE (1993) Information cascade from primary auditory-cortex to the amygdala-corticocortical and corticoamygdaloid projections of temporal cortex in the rat. Cereb Cortex 3:515–532. doi:10.1093/cercor/3.6.515
Sebban C, Tesolin-Decros B, Ciprian-Ollivier J, Perret L, Spedding M (2002) Effects of phencyclidine (PCP) and MK 801 on the EEGq in the prefrontal cortex of conscious rats; antagonism by clozapine, and antagonists of AMPA-, α1- and 5-HT2A-receptors. Br J Pharmacol 135:65–78. doi:10.1038/sj.bjp.0704451
Semenova S, Markou A (2007) The effects of the mGluR5 antagonist MPEP and the mGluR2/3 antagonist LY341495 on rats’ performance in the 5-choice serial reaction time task. Neuropharmacology 52: 863-872. doi:10.1016/j.neuropharm.2006.10.003
Spagna A, Dong Y, Mackie MA, Li M, Harvey PD, Tian Y (2015) Clozapine improves the orienting of attention in schizophrenia. Schizophr Res 168:285–291. doi:10.1016/j.schres.2015.08.009
Strauss GP, Llerena K, Gold JM (2011) Attentional disengagement from emotional stimuli in schizophrenia. Schizophr Res 131:219–223. doi:10.1016/j.schres.2011.06.001
Swart M, Liemburg EJ, Kortekaas R, Wiersma D, Bruggeman R, Aleman A (2013) Normal brain activation in schizophrenia patients during associative emotional learning. Psychiatry Res Neuroimaging 214:269–276. doi:10.1016/j.pscychresns.2013.08.008
Taylor SF, Demeter E, Phan KL, Tso IF, Welsh RC (2014) Abnormal GABAergic function and negative affect in schizophrenia. Neuropsychopharmacology 39:1000–1008. doi:10.1038/npp.2013.300
Terry AV, Schade R, Callahan PM, Chapman JM, Bartlett MG (2011) Chronic treatment with nicotine metabolite, cotinine, improves sustained attention and recognition memory in rats and attenuates glutamate (NMDA) antagonist-related impairments. Biochem Pharmacol 82:1041–1042. doi:10.1016/j.bcp.2011.07.048
Tso IF, Fang Y, Phan KL, Welsh RC, Taylor SF (2015) Abnormal GABAergic function and face processing in schizophrenia: a pharmacologic-fMRI study. Schizophr Res 168:338–344. doi:10.1016/j.schres.2015.08.022
Uehara T, Sumiyoshi T, Seo T, Itoh H, Matsuoka T, Suzuki M et al (2009) Long-term effects of neonatal MK-801 treatment on prepulse inhibition in young adult rats. Psychopathology 206:623–630. doi:10.1007/s00213-009-1527-2
Uehara T, Sumiyoshi T, Seo T, Matsuoka T, Itoh H, Suzuki M et al (2010) Neonatal exposure to MK-801, an N-methyl-D-aspartate receptor antagonist, enhances methamphetamine-induced locomotion and disrupts sensorimotor gating in pre- and post-pubertal rats. Brain Res 1352:223–230. doi:10.1016/j.brainres.2010.07.013
Uehara T, Sumiyoshi T, Hattori H, Itoh H, Matsuoka T, Iwakami N et al (2012) T-817MA, a novel neurotrophic agent, ameliorates loss of GABAergic parvalbumin-positive neurons and sensorimotor gating deficits in rats transiently exposed to MK-801 in the neonatal period. J Psychiatr Res 46:622–629. doi:10.1016/j.jpsychires.2012.01.022
Uehara T, Sumiyoshi T, Rujescu D, Genius J, Matsuoka T, Takasaki I et al (2014) Neonatal exposure to MK-801 reduces mRNA expression of mGlu3 receptors in the medial prefrontal cortex of adolescent rats. Synapse 68:202–208. doi:10.1002/syn.21734
Usiello A, Sargolini F, Roullet P, Ammassari-Teule M, Passino E, Oliverio A et al (1998) N-Methyl-D-aspartate receptors in the nucleus accumbens are involved in detection of spatial novelty in mice. Psychopathology 137:175–183. doi:10.12007/s002130050607
Weiss IC, Di IL, Feldon J, Domeney AM (2000) Strain differences in the isolation-induced effects on prepulse inhibition of the acoustic startle response and on locomotor activity. Behav Neurosci 114:364. doi:10.1037//0735.7044.114.2.364
Wilson MA, Kinsman SL, Johnston MV (1998) Expression of NMDA receptor subunit mRNA after MK-801 treatment in neonatal rats. Dev Brain Res 109:211–220. doi:10.1016/S0165-3806(98)00084-4
Zheng Y, Wu C, Li J, Wu H, She S, Liu S et al (2015) Brain substrates of perceived spatial separation between speech sources under simulated reverberant listening conditions in schizophrenia. Psychol Med 46:477–491. doi:10.1017/S0033291715001828
Zou D, Huang J, Wu X, Li L (2007) Metabotropic glutamate subtype 5 receptors modulate fear-conditioning induced enhancement of prepulse inhibition in rats. Neuropharmacology 52:476–486. doi:10.1016/j.neuropharm.2006.08.016
Acknowledgments
This study was supported by the National Clinical Key Construction Project in Chinese Medicine (2100299), the Clinical Characteristics Program of Beijing Municipal Science and Technology Commission (Z151100004015061), the National Natural Science Foundation of China (31470987), and the “985” Project of Peking University.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Wu, ZM., Ding, Y., Jia, HX. et al. Different effects of isolation-rearing and neonatal MK-801 treatment on attentional modulations of prepulse inhibition of startle in rats. Psychopharmacology 233, 3089–3102 (2016). https://doi.org/10.1007/s00213-016-4351-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-016-4351-5