Abstract
Animal models of impaired sensorimotor gating, as assessed by prepulse inhibition (PPI) of startle, have demonstrated clear validity at face, predictive, and construct levels for schizophrenia therapeutics, neurophysiological endophenotypes, and potential causative insults for this group of disorders. However, with the growing recognition of the heterogeneity of the schizophrenias, and the less sanguine view of the clinical value of antipsychotic (AP) medications, our field must look beyond “validity,” to assess the actual utility of these models. At a substantial cost in terms of research support and intellectual capital, what has come from these models, that we can say has actually helped schizophrenia patients? Such introspection is timely, as we are reassessing not only our view of the genetic and pathophysiological diversity of these disorders, but also the predominant strategies for SZ therapeutics; indeed, our field is gaining awareness that we must move away from a “find what’s broke and fix it” approach, toward identifying spared neural and cognitive function in SZ patients, and matching these residual neural assets with learning-based therapies. Perhaps, construct-valid models that identify evidence of “spared function” in neural substrates might reveal opportunities for future therapeutics and allow us to study these substrates at a mechanistic level to maximize opportunities for neuroplasticity. Such an effort will require a retooling of our models, and more importantly, a re-evaluation of their utility. For animal models to remain relevant in the search for schizophrenia therapeutics, they will need to focus less on what is valid and focus more on what is useful.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abel KM, Allin MP, Hemsley DR, Geyer MA (2003) Low doses of ketamine increases prepulse inhibition in healthy men. Neuropharmacology 44:729–737
Acheson DT, Stein MB, Paulus MP, Geyer MA, Risbrough VB (2012) The effect of pregabalin on sensorimotor gating in ‘low’ gating humans and mice. Neuropharmacology 63:480–485
Ahmari SE, Risbrough VB, Geyer MA, Simpson HB (2012) Impaired sensorimotor gating in unmedicated adults with obsessive-compulsive disorder. Neuropsychopharmacology 37:1216–1223
Angelov SD, Dietrich C, Krauss JK, Schwabe K (2014) Effect of deep brain stimulation in rats selectively bred for reduced prepulse inhibition. Brain Stimul 7(4):595–602
Angst MJ, Macedo CE, Guiberteau T, Sandner G (2007) Alteration of conditioned emotional response and conditioned taste aversion after neonatal ventral hippocampus lesions in rats. Brain Res 1143:183–192
Anticevic A, Brumbaugh MS, Winkler AM, Lombardo LE, Barrett J, Corlett PR, Kober H, Gruber J, Repovs G, Cole MW, Krystal JH, Pearlson GD, Glahn DC (2013) Global prefrontal and fronto-amygdala dysconnectivity in bipolar I disorder with psychosis history. Biol Psychiatry 73:565–573
Bakshi VP, Swerdlow NR, Geyer MA (1994) Clozapine antagonizes phencyclidine-induced deficits in sensorimotor gating of the startle response. J Pharmacol Exp Ther 271:787–794
Bhakta SG, Talledo JA, Lamb SN, Balvaneda B, Chou HH, Rana B, Young J, Light G, Swerdlow NR (2014) Effects of Tolcapone on neurocognitive and neurophysiological measures in healthy adults. Neuropsychopharmacology 39:S514
Braff D, Stone C, Callaway E, Geyer M, Glick I, Bali L (1978) Prestimulus effects on human startle reflex in normals and schizophrenics. Psychophysiology 15:339–343
Carter RJ, Lione LA, Humby T, Mangiarini L, Mahal A, Bates GP, Dunnett SB, Morton AJ (1999) Characterization of progressive motor deficits in mice transgenic for the human Huntington’s disease mutation. J Neurosci 19:3248–3257
Castellan Baldan L, Williams KA, Gallezot JD, Pogorelov V, Rapanelli M, Crowley M, Anderson GM, Loring E, Gorczyca R, Billingslea E, Wasylink S, Panza KE, Ercan-Sencicek AG, Krusong K, Leventhal BL, Ohtsu H, Bloch MH, Hughes ZA, Krystal JH, Mayes L, de Araujo I, Ding YS, State MW, Pittenger C (2014) Histidine decarboxylase deficiency causes tourette syndrome: parallel findings in humans and mice. Neuron 81:77–90
Castellanos FX, Fine EJ, Kaysen DL, Marsh WL, Rapoport JL, Hallett M (1996) Sensorimotor gating in boys with Tourette’s Syndrome and ADHD: preliminary results. Biol Psychiatry 39:33–41
Chambers RA, Sentir AM, Conroy SK, Truitt WA, Shekhar A (2010) Cortical-striatal integration of cocaine history and prefrontal dysfunction in animal modeling of dual diagnosis. Biol Psychiatry 67:788–792
Charles R, Sakurai T, Takahashi N, Elder GA, Gama Sosa MA, Young LJ, Buxbaum JD (2014) Introduction of the human AVPR1A gene substantially alters brain receptor expression patterns and enhances aspects of social behavior in transgenic mice. Dis Model Mech 7:1013–1022
Chou HH, Bhakta SG, Talledo JA, Lamb SN, Balvaneda B, Light GA, Twamley EW, Swerdlow NR (2013a) Memantine effects on MATRICS consensus cognitive performance battery in healthy adults and schizophrenia patients. Biol Psychiatry 73:273S
Chou HH, Talledo J, Lamb S, Thompson WK, Swerdlow NR (2013b) Amphetamine effects on MATRICS consensus cognitive battery performance in healthy adults. Psychopharmacology 227:165–176
Daenen EW, Wolterink G, Van Der Heyden JA, Kruse CG, Van Ree JM (2003) Neonatal lesions in the amygdala or ventral hippocampus disrupt prepulse inhibition of the acoustic startle response; implications for an animal model of neurodevelopmental disorders like schizophrenia. Eur Neuropsychopharmacol 13:187–197
Darbra S, Modol L, Llido A, Casas C, Vallee M, Pallares M (2014) Neonatal allopregnanolone levels alteration: effects on behavior and role of the hippocampus. Prog Neurobiol 113:95–105
Davis M (1984) The mammalian startle response. In Eaton RC (ed) Neural mechanisms of startle behavior. Springer Science, New York, pp 287–351
Dietz DM, Kennedy PJ, Sun H, Maze I, Gancarz AM, Vialou V, Koo JW, Mouzon E, Ghose S, Tamminga CA, Nestler EJ (2014) ΔFosB induction in prefrontal cortex by antipsychotic drugs is associated with negative behavioral outcomes. Neuropsychopharmacology 39:538–544
Driesen NR, McCarthy G, Bhagwagar Z, Bloch M, Calhoun V, D’Souza DC, Gueorguieva R, He G, Ramachandran R, Suckow RF, Anticevic A, Morgan PT, Krystal JH (2013) Relationship of resting brain hyperconnectivity and schizophrenia-like symptoms produced by the NMDA receptor antagonist ketamine in humans. Mol Psychiatry 18:1199–1204
Duncan EJ, Madonick SH, Parwani A, Angrist B, Rajan R, Chakravorty S et al (2001) Clinical and sensorimotor gating effects of ketamine in normals. Neuropsychopharmacology 25:72–83
Francis DD, Szegda K, Campbell G, Martin WD, Insel TR (2003) Epigenetic sources of behavioral differences in mice. Nat Neurosci 6:445–446
Frankland PW, Wang Y, Rosner B, Shimizu T, Balleine BW, Dykens EM, Ornitz EM, Silva AJ (2004) Sensorimotor gating abnormalities in young males with fragile X syndrome and Fmr1-knockout mice. Mol Psychiatry 9:417–425
Geyer MA, Krebs-Thomson K, Braff DL, Swerdlow NR (1991) Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology 156:117–154
Gomez-Wong E, Marti MJ, Tolosa E, Valls-Solé J (1998) Sensory modulation of the blink reflex in patients with blepharospasm. Arch Neurol 55:1233–1237
Graham F (1975) The more or less startling effects of weak prestimuli. Psychophysiology 12:238–248
Greenwood TA, Braff DL, Light GA, Cadenhead KS, Calkins ME, Dobie DJ, Freedman R, Green MF, Gur RE, Gur RC, Mintz J, Nuechterlein KH, Olincy A, Radant AD, Seidman LJ, Siever LJ, Silverman JM, Stone WS, Swerdlow NR, Tsuang DW, Tsuang MT, Turetsky BI, Schork NJ (2007) The consortium on the genetics of schizophrenia (COGS): initial heritability analyses of endophenotypic measures for schizophrenia. Arch Gen Psychiatry 64:1242–1250
Hanlon FM, Houck JM, Klimaj SD, Caprihan A, Mayer AR, Weisend MP, Bustillo JR, Hamilton DA, Tesche CD (2012) Frontotemporal anatomical connectivity and working-relational memory performance predict everyday functioning in schizophrenia. Psychophysiology 49:1340–1352
Haut KM, Lim KO, MacDonald A (2010) Prefrontal cortical changes following cognitive training in patients with chronic schizophrenia: effects of practice, generalization and specificity. Neuropsychopharmacology 35:1850–1859
Hines RM, Hines DJ, Houston CM, Mukherjee J, Haydon PG, Tretter V, Smart TG, Moss SJ (2013) Disrupting the clustering of GABAA receptor α2 subunits in the frontal cortex leads to reduced γ-power and cognitive deficits. Proc Natl Acad Sci USA 110(41):16628–16633
Hoenig K, Hochrein A, Quednow BB, Maier W, Wagner M (2005) Impaired prepulse inhibition of acoustic startle in obsessive-compulsive disorder. Biol Psychiatry 57:1153–1158
Janssen PAJ, Niemegeers CJE (1959) Chemistry and pharmacology of compounds related to 4-(4-hydroxy-Cphenyl-piperidino)-butyrophenone. Part II. Inhibition of apomorphine vomiting in dogs. Arzneimittel-Forsch 9:765–767
Johansson C, Jackson DM, Svensson L (1994) The atypical antipsychotic, remoxipride, blocks phencyclidine-induced disruption of prepulse inhibition in the rat. Psychopharmacology 116:437–442
Karten HJ (1991) Homology and evolutionary origins of the ‘Neocortex’. Brain Behav Evolution 38:264–272
Kodsi MH, Swerdlow NR (1994) Quinolinic acid lesions of the ventral striatum reduce sensorimotor gating of acoustic startle in rats. Brain Res 643:59–65
Kumari V, Gray JA, Geyer MA, Soni W, Mitterschiffthaler MT, Vythelingum GN, Simmons A, Williams SC, Sharma T (2003) Neural correlates of tactile prepulse inhibition: a functional MRI study in normal and schizophrenic subjects. Psychiatry Res 122(2):99–113
Kumari V, Peters ER, Fannon D, Antonova E, Premkumar P, Anilkumar AP, Williams SC, Kuipers E (2009) Dorsolateral prefrontal cortex activity predicts responsiveness to cognitive-behavioral therapy in schizophrenia. Biol Psychiatry 66:594–602
Kumari V, Premkumar P, Fannon D, Aasen I, Raghuvanshi S, Anilkumar AP, Antonova E, Peters ER, Kuipers E (2012) Sensorimotor gating and clinical outcome following cognitive behaviour therapy for psychosis. Schizophr Res 134:232–238
Labbate GP, da Silva AV, Barbosa-Silva RC (2014) Effect of severe neonatal seizures on prepulse inhibition and hippocampal volume of rats tested in early adulthood. Neurosci Lett 568:62–66
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. Neuropsychopharm 27:1–11
Le Pen G, Kew J, Alberati D, Borroni E, Heitz MP, Moreau JL (2003) Prepulse inhibition deficits of the startle reflex in neonatal ventral hippocampal-lesioned rats: reversal by glycine and a glycine transporter inhibitor. Biol Psychiatry 54:1162–1170
Le Pen G, Gourevitch R, Hazane F, Hoareau C, Jay TM, Krebs MO (2006) Peri-pubertal maturation after developmental disturbance: a model for psychosis onset in the rat. Neuroscience 143:395–405
Levitt JJ, Bobrow L, Lucia D, Srinivasan P (2010) A selective review of volumetric and morphometric imaging in schizophrenia. In: Swerdlow NR (ed) Behavioral neurobiology of schizophrenia and its treatment. Current Topics in Behavioral Neuroscience, Springer, pp 243–282
Lewis DA, Levitt P (2002) Schizophrenia as a disorder of neurodevelopment. Annu Rev Neurosci 25:409–432
Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Keefe RS, Davis SM, Davis CE, Lebowitz BD, Severe J, Hsiao JK (2005) clinical antipsychotic trials of intervention effectiveness (CATIE) investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 353:1209–1223
Lind NM, Arnfred SM, Hemmingsen RP, Hansen AK (2004) Prepulse inhibition of the acoustic startle reflex in pigs and its disruption by d-amphetamine. Behav Brain Res 155:217–222
Linn GS, Negi SS, Gerum SV, Javitt DC (2003) Reversal of phencyclidine-induced prepulse inhibition deficits by clozapine in monkeys. Psychopharmacology 169:234–239
Lipska BK, Jaskiw GE, Weinberger DR (1993) Postpubertal emergence of hyperresponsiveness to stress and to amphetamine after neonatal excitotoxic hippocampal damage: a potential animal model of schizophrenia. Neuropsychopharm 9:67–75
Lipska BK, Swerdlow NR, Geyer MA, Jaskiw GE, Braff DL, Weinberger DR (1995) Neonatal excitotoxic hippocampal damage in rats causes post-pubertal changes in prepulse inhibition of startle and its disruption by apomorphine. Psychopharmacology 122:35–43
Ma J, Leung LS (2014) Deep brain stimulation of the medial septum or nucleus accumbens alleviates psychosis-relevant behavior in ketamine-treated rats. Behav Brain Res 266:174–182
MacLean PD (1954) The limbic system and its hippocampal formation; studies in animals and their possible application to man. J Neurosurg 11(1):29–44
Mansbach RS, Geyer MA, Braff DL (1988) Dopaminergic stimulation disrupts sensorimotor gating in the rat. Psychopharmacology 94:507–514
Marquis JP, Goulet S, Doré FY (2006) Neonatal lesions of the ventral hippocampus in rats lead to prefrontal cognitive deficits at two maturational stages. Neuroscience 140:759–767
McAlonan GM, Daly E, Kumari V, Critchley HD, van Amelsvoort T, Suckling J, Simmons A, Sigmundsson T, Greenwood K, Russell A, Schmitz N, Happe F, Murphy DG (2002) Brain anatomy and sensorimotor gating in Asperger’s syndrome. Brain 125:1594–1606
Meltzer HY, Alphs L, Green AI, Altamura AC, Anand R, Bertoldi A, Bourgeois M, Chouinard G, Islam MZ, Kane J, Krishnan R, Lindenmayer JP, Potkin S, International Suicide Prevention Trial Study Group (2003) Clozapine treatment for suicidality in schizophrenia: international suicide prevention trial (InterSePT). Arch Gen Psychiatry 60:82–91
Miller EJ, Saint Marie LR, Breier MR, Swerdlow NR (2010) Pathways from the ventral hippocampus and caudal amygdala to forebrain regions that regulate sensorimotor gating in the rat. Neuroscience 165(2):601–611
Murray RM, Jones P, O’Callaghan E (1991) Fetal brain development and later schizophrenia. Ciba Found Symp 156:155–163
Nguyen R, Morrissey MD, Mahadevan V, Cajanding JD, Woodin MA, Yeomans JS, Takehara-Nishiuchi K, Kim JC (2014) Parvalbumin and GAD65 interneuron inhibition in the ventral hippocampus induces distinct behavioral deficits relevant to schizophrenia. J Neurosci 34:14948–14960
O’Donnell P (2012) Cortical disinhibition in the neonatal ventral hippocampal lesion model of schizophrenia: New vistas on possible therapeutic approaches. Pharmacol Ther 133:19–25
Ornitz EM, Hanna GL, de Traversay J (1992) Prestimulation-induced startle modulation in attention deficit hyperactivity disorder and nocturnal enuresis. Psychophysiology 29:437–451
Palmer DD, Henter ID, Wyatt RJ (1999) Do antipsychotic medications decrease the risk of suicide in patients with schizophrenia? J Clin Psychiatry 60(Suppl 2):100–103
Perez VB, Swerdlow NR, Braff DL, Naatanen R, Light GA (2014) Using biomarkers to inform diagnosis, guide treatments and track response to interventions in psychotic illnesses. Biomark Med 8(1):9–14
Pinnock F, Bosch D, Brown T, Simons N, Yeomans JR, DeOliveira C, Schmid S (2015) Nicotine receptors mediating sensorimotor gating and its enhancement by systemic nicotine. Front Behav Neurosci 9:30. doi:10.3389/fnbeh.2015.00030
Posch DK, Schwabe K, Krauss JK, Lütjens G (2012) Deep brain stimulation of the entopeduncular nucleus in rats prevents apomorphine-induced deficient sensorimotor gating. Behav Brain Res 232:130–136
Powell SB, Swerdlow NR (2015) Social isolation rearing and sensorimotor gating in rat models of relevance to schizophrenia: what we know, and what we don’t. In: Pletnikov M, Waddington J (eds) Modeling psychopathological dimensions of schizophrenia. Handbooks of Behavioral Neuroscience, vol 23. Elsevier, Amsterdam (in press)
Renoux AJ, Sala-Hamrick KJ, Carducci NM, Frazer M, Halsey KE, Sutton MA, Dolan DF, Murphy GG, Todd PK (2014) Impaired sensorimotor gating in Fmr1 knock out and Fragile X premutation model mice. Behav Brain Res 267:42–45
Ressler KJ, Rothbaum BO, Tannenbaum L, Anderson P, Graap K, Zimand E, Hodges L, Davis M (2004) Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear. Arch Gen Psychiatry 61:1136–1144
Ribeiro BM, do Carmo MR, Freire RS, Rocha NF, Borella VC, de Menezes AT, Monte AS, Gomes PX, de Sousa FC, Vale ML, de Lucena DF, Gama CS, Macedo D (2013) Evidences for a progressive microglial activation and increase in iNOS expression in rats submitted to a neurodevelopmental model of schizophrenia: reversal by clozapine. Schizophr Res 151:12–19
Risbrough V, Ji B, Hauger R, Zhou X (2014) Generation and characterization of humanized mice carrying COMT158 Met/Val alleles. Neuropsychopharmacology 39:1823–1832
Rohleder C, Jung F, Mertgens H, Wiedermann D, Sué M, Neumaier B, Graf R, Leweke FM, Endepols H (2014) Neural correlates of sensorimotor gating: a metabolic positron emission tomography study in awake rats. Front Behav Neurosci 8:178
Roussos P, Giakoumaki SG, Rogdaki M, Pavlakis S, Frangou S, Bitsios P (2008) Prepulse inhibition of the startle reflex depends on the catechol O-methyltransferase Val158Met gene polymorphism. Psychol Med 38:1651–1658
Ryan RT, Bhardwaj SK, Tse YC, Srivastava LK, Wong TP (2013) Opposing alterations in excitation and inhibition of layer 5 medial prefrontal cortex pyramidal neurons following neonatal ventral hippocampal lesion. Cereb Cortex 23:1198–1227
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511:421–427
Schwartz JM (1997) Brain lock: free yourself from obsessive-compulsive behavior. Regan Books, New York, p 1997
Schwartz JM (1998) Neuroanatomical aspects of cognitive-behavioural therapy response in obsessive-compulsive disorder. An evolving perspective on brain and behaviour. Br J Psychiatry Suppl 35:38–44
Schwartz JM, Stoessel PW, Baxter LR Jr, Martin KM, Phelps ME (1996) Systematic changes in cerebral glucose metabolic rate after successful behavior modification treatment of obsessive-compulsive disorder. Arch Gen Psychiatry 53:109–113
Shilling PD, Saint Marie RL, Shoemaker JM, Swerdlow NR (2008) Strain differences in the gating-disruptive effects of apomorphine: relationship to gene expression in nucleus accumbens signaling pathways. Biol Psychiatry 63:748–758
Sobin C, Kiley-Brabeck K, Karayiorgou M (2005) Lower prepulse inhibition in children with the 22q11 deletion syndrome. Am J Psychiatry 162:1090–1099
Sorenson CA, Swerdlow NR (1982) The effect of tail pinch on the acoustic startle response in rats. Brain Res 247:105–113
Stefansson H, Meyer-Lindenberg A, Steinberg S, Magnusdottir B, Morgen K, Arnarsdottir S, Bjornsdottir G, Walters GB, Jonsdottir GA, Doyle OM, Tost H, Grimm O, Kristjansdottir S, Snorrason H, Davidsdottir SR, Gudmundsson LJ, Jonsson GF, Stefansdottir B, Helgadottir I, Haraldsson M, Jonsdottir B, Thygesen JH, Schwarz AJ, Didriksen M, Stensbøl TB, Brammer M, Kapur S, Halldorsson JG, Hreidarsson S, Saemundsen E, Sigurdsson E, Stefansson K (2014) CNVs conferring risk of autism or schizophrenia affect cognition in controls. Nature 505:361–366
Sun SX, Liu GG, Christensen DB, Fu AZ (2007) Review and analysis of hospitalization costs associated with antipsychotic nonadherence in the treatment of schizophrenia in the United States. Curr Med Res Opin 23:2305–2312
Swerdlow NR (2011a) Are we studying and treating schizophrenia correctly? Schizophr Res 130:1–10
Swerdlow NR (2011b) Beyond antipsychotics: Pharmacologically-augmented cognitive therapies (PACTs) for schizophrenia. Neuropsychopharmacology 37:310–311
Swerdlow NR, Geyer MA (1993) Clozapine and haloperidol in an animal model of sensorimotor gating deficits in schizophrenia. Pharmacol Biochem Behav 44:741–744
Swerdlow NR, Braff DL, Geyer MA, Koob GF (1986) Central dopamine hyperactivity in rats mimics abnormal acoustic startle response in schizophrenics. Biol Psychiatry 21:23–33
Swerdlow NR, Keith VA, Braff DL, Geyer MA (1991) Effects of spiperone, raclopride, SCH 23390 and clozapine on apomorphine inhibition of sensorimotor gating of the startle response in the rat. J Pharmacol Exp Ther 256:530–536
Swerdlow NR, Caine SB, Braff DL, Geyer MA (1992a) The neural substrates of sensorimotor gating of the startle reflex: a review of recent findings and their implications. J Psychopharmacol 6:176–190
Swerdlow NR, Caine SB, Geyer MA (1992b) Regionally selective effects of intracerebral dopamine infusion on sensorimotor gating of the startle reflex in rats. Psychopharmacology 108:189–195
Swerdlow NR, Benbow CH, Zisook S, Geyer MA, Braff DL (1993) A preliminary assessment of sensorimotor gating in patients with obsessive compulsive disorder. Biol Psychiatry 33:298–301
Swerdlow NR, Braff DL, Taaid N, Geyer MA (1994a) Assessing the validity of an animal model of deficient sensorimotor gating in schizophrenic patients. Arch Gen Psychiatry 51:139–154
Swerdlow NR, Zisook D, Taaid N (1994b) Seroquel (ICI 204, 636) restores prepulse inhibition of acoustic startle in apomorphine-treated rats: similarities to clozapine. Psychopharmacology 114:675–678
Swerdlow NR, Paulsen J, Braff DL, Butters N, Geyer MA, Swenson MR (1995) Impaired prepulse inhibition of acoustic and tactile startle response in patients with Huntington’s disease. J Neurol Neurosurg Psychiatry 58:192–200
Swerdlow NR, Bakshi V, Waikar M, Taaid N, Geyer MA (1998) Seroquel, clozapine and chlorpromazine restore sensorimotor gating in ketamine-treated rats. Psychopharmacology 140:75–80
Swerdlow NR, Geyer MA, Braff DL (2001a) Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges. Psychopharmacology 156:194–215
Swerdlow NR, Karban B, Ploum Y, Sharp R, Geyer MA, Eastvold A (2001b) Tactile prepuff inhibition of startle in children with Tourette’s syndrome: in search of an “fMRI-friendly” startle paradigm. Biol Psychiatry 50:578–585
Swerdlow NR, Stephany N, Shoemaker JM, Ross L, Wasserman LC, Talledo J, Auerbach PP (2002) Effects of amantadine and bromocriptine on startle and sensorimotor gating: parametric studies and cross-species comparisons. Psychopharmacology 164:82–92
Swerdlow NR, Shoemaker JM, Platten A, Pitcher L, Goins J, Auerbach PP (2004) Heritable differences in the dopaminergic regulation of sensorimotor gating. I. Apomorphine effects on startle gating in albino and hooded outbred rat strains and their F1 and N2 progeny. Psychopharmacology 174:441–451
Swerdlow NR, Talledo J, Sutherland AN, Nagy D, Shoemaker JM (2006) Antipsychotic effects on prepulse inhibition in normal ‘low gating’ humans and rats. Neuropsychopharmacology 31:2011–2021
Swerdlow NR, Weber M, Qu Y, Light GA, Braff DL (2008) Realistic expectations of prepulse inhibition in translational models for schizophrenia research. Psychopharmacology 199:331–388
Swerdlow NR, van Bergeijk DP, Bergsma F, Weber E, Talledo J (2009) The effects of memantine on prepulse inhibition. Neuropsychopharmacology 34:1854–1864
Swerdlow NR, Light GA, Breier MR, Shoemaker JM, Saint Marie RL, Neary AC, Geyer MA, Stevens KE, Powell SB (2012a) Sensory and sensorimotor gating deficits after neonatal ventral hippocampal lesions in rats. Dev Neurosci 34:240–249
Swerdlow NR, Shilling PD, Breier M, Trim RS, Light GA, Marie RS (2012b) Fronto-temporal-mesolimbic gene expression and heritable differences in amphetamine-disrupted sensorimotor gating in rats. Psychopharmacology 224:349–362
Swerdlow NR, Bhakta SG, Talledo JA et al (2013a) Sensorimotor gating predicts sensitivity to pro-attentional effects of amphetamine in healthy adults. Society for Neuroscience, San Diego, 9–13 Nov 2013
Swerdlow NR, Powell SB, Breier MR, Hines SR, Light GA (2013b) Coupling of gene expression in medial prefrontal cortex and nucleus accumbens after neonatal ventral hippocampal lesions accompanies deficits in sensorimotor gating and auditory processing in rats. Neuropharmacology 75:38–46
Swerdlow NR, Light GA, Sprock J, Calkins ME, Green MF, Greenwood TA, Gur RE, Gur RC, Lazzeroni LC, Nuechterlein KH, Radant AD, Ray A, Seidman LJ, Siever LJ, Silverman JM, Stone WS, Sugar CA, Tsuang DW, Tsuang MT, Turetsky BI, Braff DL (2014) Deficient prepulse inhibition in schizophrenia detected by the multi-site COGS. Schizophr Res 152:503–512
Swerdlow NR, Bhakta S, Chou HH, Talledo JA, Balvaneda B, Light GA (2015) Memantine effects on sensorimotor gating and mismatch negativity in patients with chronic psychosis. Neuropsychopharmacology (in press). doi:10.1038/npp.2015.162)
Taub E, Uswatte G, Elbert T (2002) New treatments in neurorehabilitation founded on basic research. Nat Rev Neurosci 3:228–236
Uehara T, Sumiyoshi T, Seo T, Matsuoka T, Itoh H, Suzuki M, Kurachi M (2010) Neonatal exposure to MK-801, an N-methyl-D-aspartate receptor antagonist, enhances methamphetamine-induced locomotion and disrupts sensorimotor gating in pre- and postpubertal rats. Brain Res 1352:223–230
Vaillancourt C, Boksa P (2000) Birth insult alters dopamine-mediated behavior in a precocial species, the guinea pig. Implications for schizophrenia. Neuropsychopharmacology 23:654–666
Valls-Sole J, Munoz JE, Valldeoriola F (2004) Abnormalities of prepulse inhibition do not depend on blink reflex excitability: a study in Parkinson’s disease and Huntington’s disease. Clin Neurophysiol 115:1527–1536
van Rijn S, Swaab H, Magnée M, van Engeland H, Kemner C (2011) Psychophysiological markers of vulnerability to psychopathology in men with an extra X chromosome (XXY). PLoS ONE 6:e20292
Vazquez-Roque RA, Solis O, Camacho-Abrego I, Rodriguez-Moreno A, Cruz Fde L, Zamudio S, Flores G (2012) Dendritic morphology of neurons in prefrontal cortex and ventral hippocampus of rats with neonatal amygdala lesion. Synapse 66:73–382
Vollenweider FX, Barro M, Csomor PA, Feldon J (2006) Clozapine enhances prepulse inhibition in healthy humans with low but not with high prepulse inhibition levels. Biol Psychiatry 60:597–603
Weinberger DR (1987) Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 44:660–669
Zhu F, Zhang L, Ding YQ, Zhao J, Zheng Y (2014a) Neonatal intrahippocampal injection of lipopolysaccharide induces deficits in social behavior and prepulse inhibition and microglial activation in rats: Implication for a new schizophrenia animal model. Brain Behav Immun 38:166–174
Zhu F, Zheng Y, Ding YQ, Li Y, Zhang X, Wu R, Guo X, Zhao J (2014b) Minocycline and risperidone prevent microglia activation and rescue behavioral deficits inducted by neonatal intrahippocampal injection of lipopolysaccharide in rats. PLoS ONE 9:393966
Acknowledgements
NRS is supported by NIMH awards MH59803, MH93453, MH42228, and MH094320. GL is supported by MH42228, MH065571, MH094151, MH093453, MH094320, UL1TR000100, MH081944, NARSAD, the Veterans Medical Research Foundation, and the VISN-22 Mental Illness, Research, Education, and Clinical Center. GL has served as a consultant for Astellas Inc, Forum, and Neuroverse for work unrelated to this chapter. The authors have no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Swerdlow, N.R., Light, G.A. (2015). Animal Models of Deficient Sensorimotor Gating in Schizophrenia: Are They Still Relevant?. In: Robbins, T.W., Sahakian, B.J. (eds) Translational Neuropsychopharmacology. Current Topics in Behavioral Neurosciences, vol 28. Springer, Cham. https://doi.org/10.1007/7854_2015_5012
Download citation
DOI: https://doi.org/10.1007/7854_2015_5012
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-33911-5
Online ISBN: 978-3-319-33913-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)