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Animal Models for Schizophrenia Research
Printable versionPrintable version Unless otherwise specified, organism is mouse.
Name DA-related behavior Gating Cognitive behavior Social behavior Molecular and/or Morphological Signature Response to APD
Monkey Fetal Irradiation     Impaired working memory   Mid-gestational irradiation decreases both gray and white matter in frontal cortex.  
Mouse Prenatal Immune Challenge: Human Influenza Virus Decreased open field exploration Impaired PPI   Impaired social interaction Reduced reelin expression in cortex layer 1; increased pyramidal cell density; cortical and callosal atrophy; reduced 5-HT levels in cerebellum atrophy; altered expression of myelination genes in the cerebellum; reduced 5-HT levels in cerebellum; increased 5-HT2A receptor expression in frontal cortex Clozapine and chlorpromazine increase PPI – hyper-reversal of PPI deficit
Mouse Prenatal Immune Challenge: PolyI:C (Delivery Timing Varies) No change in total distance traveled in open field but reduced center exploration; increased response to amphetamine and MK-801 (emerges after puberty; not rescued by cross-fostering) Disrupted PPI (post-puberty; deficits not rescued by cross-fostering) Reduced escape latency in Morris water maze; impairment in novel object recognition memory; deficits in latent inhibition (post-puberty; deficits not rescued by cross-fostering); electrophysiology: reduced theta oscillation generated in the CA1 area of the hippocampus Reduced social interaction Increased DA turnover and reduced binding to D2 receptors in striatum; reduced reelin- and parvalbumin- expressing neurons in PFC; reduced DA levels and D1 receptors in PFC; increased TH expression in striatum; reduced density of cerebellar Purkinje cells; delayed myelination of hippocampus; reduced parvalbumin-expressing neurons in the hippocampus; enlargement of lateral ventricles; impaired synaptic development of upper-layer neurons Disrupted PPI was improved by clozapine and chlorpromazine; deficits in latent inhibition and novel object recognition memory were improved by clozapine but not haloperidol; deficits in Morris water maze were improve by clozapine
Mouse Prenatal Restraint Stress Increased novelty induced locomotor activity; enhanced MK-801induced locomotion Impaired PPI Deficits in object recognition memory and contextual fear conditioning Reduced social interaction Abnormal Purkinje cell growth and dendritic atrophy; glial deficits in the hippocampus (female specific); over-expression of DNMTs mRNA in the frontal cortex; decreased GAD67, reelin, and mGlu2 and mGlu3 receptor protein levels in the frontal cortex; altered neuronal migration Clozapine reversed deficits in PPI and social interaction; increased locomotive response to MK-801 was attenuated by clozapine; phenotypic rescue with mGluR2/3 agonist or valproic acid
Mouse Prenatal Variable Stress (GD1-7)     Altered learning and memory during a modified Barnes maze task (sex specific; timing specific)   Increased plasma glucocorticoid levels following stress; altered expression of glucocorticoid receptor expression in the hippocampus; dysmasculinization of offspring and second generation offspring (paternal stress lineage) via epigenetic programming  
Rat 24 hour Maternal Deprivation on Post-natal Day 9   Disrupted PPI, Effect develops after puberty.     Males only: neuronal degeneration and increased GFAP+ cells in cerebellum; neuronal degeneration and increased astrocytes in hippocampus Both sexes: altered cannabinoid receptor expression in hippocampus; increased plasma glucocorticoid levels; increased levels of 5- HT in the prefrontal cortex, hippocampus, and striatum (some changes sex dependent); increased levels of DA in the prefrontal cortex and striatum Haloperidol reverses PPI deficit.
Rat Antimitotic Agent – MAM or AraC Enhanced response to amphetamine and MK-801 (post-puberty) Disrupted PPI (post-puberty) Learning deficits in Morris water maze, object recognition, and attentional set-shifting; no change in 5-choice serial reaction time task Decreased social interaction (deficit present prior to puberty) Reduced hippocampal volume; alterations of NMDAR protein levels and function in the hippocampus; increased neuron density in prefrontal cortex; enhanced NAc DA release to amphetamine; increased firing of dopaminergic neurons; enlarged lateral and third ventricles Increased response to MK-801 was attenuated by risperidone, haloperidol, and clozapine
Rat Isolation Rearing Enhanced amphetamine-induced locomotion and DA release (strain-dependent) Disrupted PPI (strain-dependent) Performance on Morris water maze and T-maze appears normal Impaired novel object recognition, attentional set-shifting, and performance on Morris water maze Increased social interaction and aggression (males); impaired social recognition Reduced PFC volume (neuron # unchanged) and GAT-1 expression; altered accumbal protein expression (some correlated with PPI deficits); reduced accumbal dendritic length and spine density; altered NMDA receptor mRNA and protein expression in the hippocampus and prefrontal cortex; enhanced amplitudes of hippocampal voltage-dependent transient outward K+ currents Raclopride reversed PPI deficit
Rat Maternal Malnutrition Enhanced amphetamine- but not MK-801-induced locomotion and apomorphine-induced stereotopy; (females only with post-pubertal onset) Disrupted PPI (females only with post-pubertal onset)     Increases in NMDA receptor binding (sex- and region-specific); increased DA receptor binding and decreased DA transporter binding in striatum (females only)  
Rat Neonatal Immune Challenge: Borna Disease Virus Enhanced novelty induced locomotor activity in Fisher rats; enhanced amphetamine-induced locomotion Disrupted PPI in Fisher rats Reduced social interaction   Impairs BDNF synaptogenesis; prefrontal cortex thinning; loss of cerebellar Purkinje neurons; increased norepinephrine and 5-HT levels in cortex and cerebellum (post-pubertal)  
Rat Placental Insufficiency/Birth Insults Enhanced amphetamine-induced locomotion and accumbal dopamine release Disrupted PPI (post-pubertal onset) Performance on Morris water maze and T-maze appears normal   Reduced DA release in PFC, increased DAT in NAc (basal), decreased DA receptor expression; reduced dentate granule cells; region- and age-specific alterations in dendritic spine development; altered expression of presynaptic genes; decreased caudate-putamen volume PPI deficits reversed by clozapine
Rat Prenatal Immune Challenge: LPS Increased amphetamine-induced locomotion Enhanced acoustic startle; disrupted PPI (worse in males) Impaired object recognition (post-puberty) Reduced social interaction, possibly due to increased anxiety Reduced dendritic complexity in PFC and hippocampus; increased accumbal DA and striatal DOPAC; elevated serum and fetal brain cytokine levels; altered frontal synaptophysin expression; reduced parvalbumin-expressing neurons in the hippocampus; down regulated expression of several genes involved in neurogenesis and neuronal migration; (direction of some changes are age-dependent) PPI deficit and elevated serum cytokines both reversed by haloperidol
Rat Prenatal Immune Challenge: PolyI:C (Delivery Timing Varies) Increased response to amphetamine (emerges after puberty); in moms that lost or gained little weight offspring showed attenuated hyperactivity in response to MK-801 Disrupted PPI (possibly sex dependent) Disrupted latent inhibition (post-puberty); impaired novel object recognition; classical fear conditioning, active avoidance, water maze and discrimination learning appear normal   Amphetamine-induced DA release increased; increased hippocampal pyknotic cells Deficit in latent inhibition was improved by clozapine and haloperidol; altered response to amphetamine was attenuated by adolescent treatment with fluoxetine and aripiprazole
Rat Prenatal Restraint Stress Increased novelty induced locomotor activity No disruption in PPI Memory deficits during Y maze and radial arm maze; no apparent deficits in latent inhibition, may or may not show spatial memory defict in water maze task   Increased expression of D2-like and NMDA receptors in the frontal cortex and hippocampus; prolonged corticosterone stress response and decreased expression of central corticosteroid receptors (sensitive to cross-fostering); increased basal dopamine and decreased noradrenaline output in the nucleus accumbens; decreased basal noradrenaline output in the prefrontal cortex; apical dendritic atrophy and altered spine density in the hippocampus; decrease neurogenesis in hippocampus Maternal fluoxetine treatment improves hippocampal neurogenesis and reverses anxiety behaviors in stressed offspring
Rat Prenatal Variable Stress Increased response to amphetamine and PCP with post-pubertal onset Disrupted PPI and N40 Impaired object and social recognition; deficits in Morris water maze; impaired cued and contextual fear conditioning; impairment in sustained attention and inhibitory response control Impaired social interaction present in adolescent and adult rats; reversal by oxytocin; no effect of cross-fostering NMDA, GABAergic and presynaptic protein dysregulation; reduced hippocampal neurogenesis and hippocampal volume; decreased BDNF protein expression in the hippocampus (strain dependent); altered pattern of apical dendritic maturation of pyramidal neurons (males only) Social interaction deficit not improved by haloperidol
Rat Prenatal Vitamin D Insufficiency Enhanced MK-801induced locomotion; enhanced amphetamine-induced locomotion (females only) No disruption in PPI   No deficit in social behavior Enlarged lateral ventricles; thinned cortex; altered brain expression of proteins involved in mitochondrial function, calcium homeostasis, and synaptic plasticity; decreased neurogenesis Haloperidol ameliorated effects on neurogenesis
Rodent Prenatal Immune Challenge: PolyI:C (delivery timing varies) No change in total distance traveled in open field but reduced center exploration; increased response to amphetamine and MK-801 (emerges after puberty)--not rescued by cross-fostering Disrupted PPI and changes in latent inhibition (post-puberty); PPI deficit not rescued by cross-fostering Reduced escape latency in Morris water maze; impairment n novel object recognition memory and latent inhibition (post-puberty); classical fear conditioning, active avoidance and discrimination learning appear normal Reduced social interaction Amphetamine-induced DA release increased; increased hippocampal pyknotic cells; increased DA turnover and reduced binding to D2 receptors in striatum; reduced reelin- and parvalbumin- expressing neurons in PFC; reduced D1 receptors in PFC; increased TH expression in striatum; reduced density of cerebellar Purkinje cells; delayed myelination of hippocampus Deficits in latent inhibition and novel object recognition memory are improved by clozapine but not haloperidol
Printable versionPrintable version Unless otherwise specified, organism is mouse.
Name DA-related behavior Gating Cognitive behavior Social behavior Molecular and/or Morphological Signature Response to APD
Basolateral Amygdala Picrotoxin Infusion-Rat           GABA antagonism in BLA decreases GAD67 in HPC, GABA antagonism in BLA increases HPC LTP
Ceftriaxone-Induced Glutamate Transporter Upregulation   Impairs PPI.        
CHX Induced Glutathione Depletion     Disrupted short-term spatial memory   Reduced striatal and cortex glutathione levels  
Disinhibition of Ventral Hippocampus Increased locomotor activity Disrupted PPI Disrupted fear conditioning   Increased accumbens and cortex dopamine Haloperidol and clozapine block hyperactivity but no effect on PPI deficit
Methamphetamine Treatment-Chronic   Disrupted PPI Impaired recognition memory   Increased TUNEL-positive cells in mPFC Memory impairment blocked by GABA(B) agonist, PPI disruption and TUNEL-positive cell counts blocked by olanzapine and risperidone
Neonatal EGF Treatment Increased locomotor activity Impaired PPI   Reduced social behavior Enhanced cAMP response to D2R activation Haloperidol reduced motoric activity, clozapine improved social deficit
NMDA Receptor Antagonist Rx (MK801, PCP, Ketamine)-Acute Increases locomotor activity and stereotopy, ataxia Disrupted PPI 1 day after PCP, and 15 minutes after PCP, but not 7 or 28 days later, abnormal latent inhibition Decreased working memory, disrupted fear conditioning, long-term spatial memory deficits, impaired passive-avoidance, recognition memory deficit Impaired social interaction Impaired LTP, decreased AMPA receptor density Enhanced locomotor responses blocked by APD, glycine transporter-1 inhibition rescues LTP, PPI disruption attenuated by admatine, glycine, D-serine, not D-cycloserine, fear conditioning disruption prevented by clozapine, but not haloperidol, LI abnormalities reversed by risperidone and M100907, passive avoidance impairment reversed by lurasidone, recognition memory deficit reversed by clozapine and D-serine, but not haloperidol
Printable versionPrintable version Unless otherwise specified, organism is mouse.
Name DA-related behavior Gating Cognitive behavior Social behavior Molecular and/or Morphological Signature Response to APD
Adenosine Kinase Transgenic Mice Reduced locomotor response to amphetamine; enhanced locomotor response to MK-801   Learning deficits in Morris water maze and Pavlovian conditioning   Overexpression of adenosine kinase; reduced levels of adenosine in brain  
AKT1 KO Mice Normal activity in open field No baseline PPI in males, baseline PPI deficit in females (Chen; Emamian did not find PPI deficit in either sex at baseline); PPI deficit caused by amphetamine No impairment in spatial learning     Antipsychotics did not normalize PPI in females, but GSK inhibitors did
Alpha-CaMKII KO, Heterozygous Increased locomotor.   Deficits in working memory. Increased aggressive behavior. Impaired neuronal development in the dentate gyrus.  
AMPA GluR4 KO mice Normal activity in open field; increased sensitivity to MK-801 Reduced startle response; PPI deficits Impaired spatial learning, but enhanced performance in reversal learning Increased social interaction with familiar cagemate    
AMPAR GluR1 Subunit KO Hyperactive, no effect of MK-801 on locomotor behavior PPI deficit Disrupted spatial working memory Disorganized social behaviors Slowed extracellular DA clearance in striatum Anxiety prone; Hyperactivity reversed by haloperidol
Aph1B/C KO Enhanced hyperactivity in response to amphetamine PPI deficits, hypersensitive to MK-801 (increased PPI deficits) Impaired working memory on Morris water maze   Enhanced DA turnover in ventral striatum; gamma-secretase dependent cleavage of Nrg1 is impaired Haloperidol and clozapine reverse PPI deficits
Apomorphine Susceptible Rat Enhanced locomotor response to novel open field Disrupted PPI and diminished latent inhibition; Visual and acoustic PPI deficits; Sprague-Dawley rats more sensitive t     Preferential mobilization of NMDAR NR1 subunits in D1R containing neurons of the nucleus accumbens  
BACE1 KO Increased novelty-induced hyperactivity; hypersensitivity to locomotor effects of MK-801 PPI deficits Working memory deficits; impaired in inhibitory avoidance task Alterations in social recognition Impaired processing of NRG1; decreased spine density and mature spines in CA1 Clozapine attenuates novelty-induced hyperactivity and normalizes PPI deficits
Beta-arrestin 2 KO Decreased locomotor response to amphetamine       Normal DARRPP-32 phosphorylation after amphetamine  
Brattleboro (vasopressin-deficient) rats Hyperactive in novel setting Increased acoustic startle and decreased PPI   Impaired social discrimination Point mutation in gene for vasopressin; decreased dopamine concentration in frontal cortex PPI deficit reversed by acute clozapine and risperidone; chronic but not acute haloperidol reverses deficit
Calcineurin Agamma KO Enhanced response to amphetamine Disrupted PPI and latent inhibition Disrupted PPI and latent inhibition Impaired social interaction Inducible KO  
Cannabinoid Receptor 1 (CB1) KO Decreased PCP-induced locomotion     No effect on social interaction    
Cannabinoid receptor 2 KO Hypoactive in open field; enhanced hyperactivity in response to cocaine PPI deficit Impaired memory consolidation     PPI deficit improved by risperidone
Catecholamine O-methyl transferase (COMT) KO No potentiation of amphetamine-induced locomotion   Impaired recognition memory in heterozygous only No deficit in sociability or social novelty in KO or hets Increased DOPAC, D1 and D2 unchanged Increased anxiety and aggression
Chakragati Mouse (ckr) Circling, hyperactive PPI and latent inhibition deficits   Reduced social interactions Enlarged ventricles  
Chromosome 22 Deletion   Disrupted PPI Impaired cognitive function      
Chromosome 22q11.2 Deletion Model-Df(16)A Mice Hyperactive in novel environment PPI deficit Impaired fear conditioning; spatial learning deficit   Reduced dendritic spines in HPC; reduced hippocampal-prefrontal synchrony  
Chromosome 22q11.2 Deletion Model-Lgde1 Mice Normal activity in open field PPI deficit Normal fear conditioning   Disrupted cortical neurogenesis and interneuron migration  
Chromosome 22q11.2 deletion-Df1 mice   Disrupted PPI Impaired cognitive function   Haploinsufficiency of Tbx1 and Gnb1l responsible for PPI deficit  
Combined Grin D481N/K483Q Point Mutation Nonhabituating hyperactivity Increased startle response, no PPI deficit Impaired spatial learning Impaired nest building Reduced NMDAR glycine affinity; reduced LTP in hippocampus Clozapine and haloperidol did not reduce hyperactivity
Complexin I KO Decreased amphetamine-induced locomotion   No cognitive deficits in two-choice swim tank Social deficits; no preference for social novelty; no aggressive behavior in resident-intruder paradigm    
Complexin II KO     Decreased LTP; reduced Morris water maze performance only after stress      
D-Amino Acid Oxidase Deficient Mice-ddy/DAO Strain Hypoactive in open field; attenuated response to PCP Increased startle amplitude; no PPI deficit (Almond; enhanced PPI found by Zhang)        
DBA/2 Mouse   Disrupted N40 gating and PPI     Decreased levels Glu, tau and GABA in hippocampus Phenotype reversed by a7-nicotinic and α4β2 receptor agonist; by olanzapine via alpha7-nicotinic receptor; by gestational choline supplementation; by baclofen and clozapine
Densin-180 (LRRC7) KO mice Hypoactive in familiar setting; hyperactive in novel setting PPI deficits Impaired spatial memory; Impaired novel object recognition Impaired nest-building; increased aggression Impaired LTD; altered morphology of dendritic spines  
DISC 129S6/SvEv Mouse     Working memory deficit   DISC1 mutation; deficit in hippocampal short term plasticity; altered organization of neurons in dentate gyrus  
DISC 129S6/SvEv Mouse (25-bp deletion in exon 6)     Working memory deficit   DISC1 mutation; deficit in hippocampal short term plasticity; altered organization of neurons in dentate gyrus  
DISC1 Dominant-Negative Transgenic Mice Hyperactive in open field No PPI deficit No impairment in working memory in T-maze or spatial learning in water maze Impaired social interaction Decreased cortical parvalbumin-containing cells  
DISC1 KO Enhanced locomotor activity Disrupted PPI; Decreased latent inhibition   Impaired social interaction Decreased cortical parvalbumin-containing cells, accelerated neurogenesis with aberrant connectivity  
DISC1 L100P Missense Mutation Increased locomotor activity; enhanced response to amphetamine Disrupted PPI; Decreased startle amplitude Working memory impaired in T-maze; normal spatial learning in water maze   Reduced brain volume; reduced dendritic spine density; increased striatal dopamine receptors Clozapine and haloperidol reversed PPI deficit; genetic inactivation of GSK-3alpha improves PPI, hyperactivity and dendritic spine abnormalities
DISC1 mutant (exon 2/3 deletion) Normal activity in open field PPI deficit No impairment in working memory or novel object recognition Increased social interaction No morphological changes; altered threshold for LTP  
Disc1tr (Truncated) Mouse Increased immobility Impaired conditioning of latent inhibition     Enlarged ventricles; reduced parvalbumin neurons in hippocampus and mPFC  
Disc1tr (truncated, exons 1-8) Mouse Increased immobility Impaired conditioning of latent inhibition     Enlarged ventricles; reduced Parvalbumin neurons in hippocampus & mPFC  
Disheveled 1 KO   Disrupted PPI   Impaired social interaction    
Dopamine Transporter KO Increased DA and decreased D1R, D2R, hyperactive Disrupted PPI Impaired adaption to environmental changes in Morris water maze Impaired social behavior Decreased LTD in hippocampus More aggressive; impairments in Morris water maze reversed by haloperidol and acute nicotine treatment; LTD reversed by haloperidol
Dysbindin-1, Sandy (sdy) Mouse Delayed hyperactivity in novel environment; less active in open field   Object recognition deficit; impaired long-term memory retention and working memory Decreased social interaction DTNBP1 mutation with lack of dysbindin protein; increase in DA metabolism in different brain regions; reduced snapin in hippocampus; decreased DA levels in cortex, hippocampus and hypothalamus; altered kinetics of transmitter release  
Erb2/4 CNS KO Mice Normal locomotor behavior PPI deficit in males only   Increased aggression Reduced dendritic spine density Clozapine reduced behavioral changes
ErbB4 KO Reduced spontaneous activity; hyperactivity in open field   Reduced Morris water maze learning   Reduced myelination, enhanced DA receptor expression  
FEZ1 KO Hyperactive; enhanced response to MK-801 and methamphetamine       Increased methamphetamine-induced DA release in nucleus accumbens  
FGFR1 Catecholaminergic Neuron Targeted Knockout Mice Hyperactive in open field Increased startle response; PPI deficits   Decreased social interaction Increased striatal dopamine metabolites PPI deficit reversed with flupenthixol, quetiapine and clozapine; clozapine did not reduce hyperactivity
Fut8 (alpha1,6-fucosyltransferase) KO Mice Hyperactive in novel setting PPI deficit Impaired working memory Decreased social interaction   Hyperactivity reduced by haloperidol
GABAAalpha3 Receptor KO Spontaneous locomotor activity slightly increased but not after amphetamine Disrupted PPI       PPI defect improved by haloperidol Rx
Galphas Overexpression in Forebrain Hyperlocomotion PPI deficit Impaired hippocampus-dependent learning and memory retrieval   Enlarged ventricles PPI deficits reversed by haloperidol and rolipram
GAP-43 KO Hyperactive in open field, reduced anxiety Disrupted PPI        
GDI1 Knockout     Impaired short-term memory Diminished social behavior   Less aggression
GLAST (EAAT1) KO Locomotor hyperactivity in novel environment; exaggerated hyperactivity in response to MK-801         Phenotype normalized by haloperidol and mGlu2/3 agonist
Glutamate Carboxypeptidase II (GCP II) Heterozygous KO Mice Hyperactive in open field No PPI deficit Mild impairment in spatial working memory Decreased social interaction    
Glutamate-Cysteine-Ligase Modifier (GCLM) KO Mice Hyperactive in novel setting (Kulak; not found by Cole); potentiated locomotor response to amphetamine No PPI deficits (Cole); mild PPI deficit (Kulak) Normal spatial working memory and spatial learning Abnormal social preference (Kulak) Glutathione deficiency  
Glycine Transporter KO Locomotor response to psycho-stimulants same as wild-type Reduced sensitivity to amphetamine to disrupt PPI but more MK-801 induced disruption Improves memory retention   Increased NMDA receptor expression and function  
Grin1D481N   Persistent latent inhibition Spatial recognition impairments Social approach deficits Reduced NMDAR glycine affinity Phenotype reversed by D-serine treatment
Grin1D481N NR1 Point Mutation   Persistent latent inhibition; no PPI deficit; increased startle reactivity Spatial recognition impairments Social approach deficits Reduced NMDAR glycine affinity; reduced LTP in hippocampus Phenotype reversed by D-serine treatment as well as D-amino acid oxidase gene deletion
GSK-3beta Knockout   Disrupted PPI correlates with enzyme activity; no PPI disruption (Bersudsky)        
HB-EGF Forebrain-Specific KO Mice Hyperactive in novel setting and home cage PPI deficits Impaired novel object recognition Decreased social interaction Reduced dopamine, serotonin, PSD-95 and NR1 in prefrontal cortex Hyperactivity reduced by haloperidol and clozapine; PPI deficits reduced by risperidone and clozapine; clozapine but not haloperidol improved social behavior
Heterozygous Nurr1 KO Hyperactive in novel environment and also after amphetamine   Decreased emotional memory   Reduced DA turnover in striatum; Increased DA turnover in PFC Haloperidol reverses spontaneous hyperactivity
Heterozygous Reeler Mouse Enhanced mesolimbic dopamine Cross-modal PPI deficits, no unimodal PPI deficit Decreased working memory; no decrease in prefrontal cortex dependent task Impaired social interaction Reduced GAD 67, increased DNA methylation; increased truncated TrkB receptor, decreased BDNF/TrkB signaling in frontal cortex  
Heterozygous Tbx1 and Gnb1 KO   Reduced PPI        
Homer1 KO Hypoactive; enhanced locomotor behavior to MK-801 and methamphetamine Disrupted PPI (Szumlinski; not found by Jaubert) Decreased radial arm maze performance Increased social interaction; increased aggression in heterozygotes; impaired nest-building Decreased glutamate release in PFC following cocaine Rx  
Homer1a KO Enhanced locomotor behavior to MK-801 and methamphet-amine Disrupted PPI Decreased radial arm maze performance   Decreased glutamate release in PFC following cocaine Rx  
Imprinting Center Deletion Model Of PWS Hypoactive in open field Increased acoustic startle; PPI deficit Impaired attention in serial reaction time task      
Inducible Mutant hDISC1 Mice Spontaneous hyperactivity   Deficient spatial memory in females Alterations in social interaction Attenuation of neurite outgrowth in cortical neurons; enlarged ventricles  
Insulin Receptor KO   Decreased startle amplitude     Decreased insulin receptor and Akt signaling; reduced phosphorylated GSK-3 Clozapine alleviates insulin resistance
LPA1 Receptor KO mice Reduced activity in novel setting; impaired habituation PPI deficit Impaired spatial working and reference memory   Abnormal expression and phosphorylation of NMDA and AMPA subunits  
LRRTM1 KO Mice Hypoactive in novel settings   Deficit in spatial memory in water maze task Deficit in social recognition Reduced hippocampal volume and synaptic density  
MCH KO Mice Increased basal locomotor activity; hypersensitive locomotor response to d-amphetamine          
mGluR1 Knockout   Disrupted PPI       Not reversed by raclopride
mGluR5 Knockout Abnormal locomotor patterns; increased sensitivity to hyperlocomotive effects of MK-801 Disrupted PPI Short term spatial memory deficits     APD not effective; clozapine reversed PPI deficit and ameliorated locomotor disruption (Gray)
Midkine (Mdk) KO Mice Normal activity in open field PPI deficit Normal novel object recognition Decreased social contacts, but increased time per contact Reduced dopamine, D1R and D2R in striatum  
NCAM-180 KO   Disrupted PPI, no changes induced by apomorphine Rx       Increase lateral ventricle size
NCAM-EC overexpressing mice Hyperactive in open field; enhanced response to amphetamine and MK-801 PPI deficit Decreased LTP in PFC, normal LTP in HPC; impaired working memory Normal sociability Abnormal GABAergic interneurons PPI deficit reversed by clozapine but not haloperidol
Neuregulin 1 Hypomorph (Transmembrane Domain) Hyperactive in open field test Disrupted PPI No impairment in spatial learning or working memory but diminished social recognition memory Increase in dominance related and aggressive behavior depending on environment Reduced NMDA receptor activity; increased serotonin 2A receptors and serotonin transporters in CNS Open field behavior reversed by clozapine but not PPI
Neuregulin-1 Heterozygous Knockout Of EGF-Like Domain Mice Hyperactive in open field (Duffy; not replicated by Ehrlichman or Moy); normal exploratory behavior No PPI deficit Normal novel object exploration Decreased social interaction (Ehrlichman; increased sociability but decreased social novelty preference found by Moy)    
Neuregulin-1 Heterozygous Knockout Of Ig-Like Domain Mice Normal activity in open field   Impaired latent inhibition     Clozapine reduced activity in open field
Neuregulin-1 Overexpression In Mice Hyperactive in novel setting (Kato; not found by Deakin); impaired performance on rotarod Increased startle response and PPI deficits (Deakin, not found by Kato) Impaired context-dependent fear conditioning Impaired nest-building; decreased social interaction, increased aggression    
Neuregulin-1 Type II Hypomorphic Rats Normal activity in open field; impaired habituation in males, enhanced habituation in females Enhanced habituation; PPI deficit in females     Increased basal corticosterone levels  
Neurexophillin 3 KO Reduced rotorod performance Disrupted PPI but increased startle response     Expressed in Cajal-Retzius cells  
Neuropeptide Y Receptor 2 (Y2) Knockout mice Hyperactive in open field PPI in males Normal working memory and reference memory Increased social interaction in males    
Neuropeptide Y Receptor 1 (Y1) KO mice   Reduced startle response; impaired habituation; no PPI deficit        
Neurotensin-1 receptor KO mice Hyperactive in open field; no effect of PCP on locomotor activity; enhanced hyperactivity in response to amphetamine No PPI deficit (Feifel)     Decreased glutamate and NMDA-2A subunit concentration; increased striatal dopamine  
Neurotensin-2 receptor KO mice Hyperactive in open field (Liang; – not found by Feifel) Enhanced PPI in males     Increased striatal dopamine  
NgR1 KO Mildly hypoactive Strain-background dependent absence of PPI Reduced spatial working memory      
Nitric oxide synthase KO mice Hyperactive in novel setting No PPI deficit Impaired spatial memory; impaired contextual fear conditioning Increased social interaction; reduced social novelty preference    
NMDA NR1 Receptor Hypomorph Enhanced response to amphetamine Disrupted PPI   Impaired social interaction 95% reduction in NR1 expression Behaviors improved by APD
Nogo-A KO mice Enhanced hyperactivity in response to amphetamines PPI deficit Perseverative behavior; normal spatial learning      
nPAS 1/3 KO Enhanced open field locomotion Disrupted PPI Decreased social recognition   Reduced reelin interneurons  
Nurr1 Heterozygous KO Hyperactive in novel environment and also after amphetamine; enhanced response to MK-801 Disrupted PPI in males but not females Decreased emotional memory; intact spatial memory No social interaction deficit Reduced DA turnover in striatum; Increased DA turnover in PFC Haloperidol reverses spontaneous hyperactivity
Oxytocin and Oxytocin Receptor KO   PCP treatment induces large deficits in PPI   Impaired social discrimination   More aggressive
P35 (CDK5 Activator) Heterozygous Knockout Mice No locomotor abnormalities PPI deficit in females, not males Reversal learning impaired in females Social interaction deficit in males    
PACAP KO Mice Hyperactive in open field PPI deficit   Reduced social interaction   Hyperactivity reduced with risperidone; PPI deficit reversed by risperidone; social interaction deficit and hyperactivity reduced when animals raised in enriched environment
PDE4B KO Reduced baseline motor activity; exaggerated locomotor response to amphetamine Decreased PPI No deficit in Morris water maze   Decreased striatal DA and 5-HT activity  
PDGFR-beta KO mice   PPI deficit Impairment in fear conditioning Decreased social interaction Reduced GABAergic neurons in HPC, PFC and amygdala  
PGE2 EP2 KO mice Normal activity in open field PPI deficit Normal spatial memory; impaired fear conditioning Impairment in social habituation    
Phosphodiesterase 1B KO Enhanced behavioral response to methamphetamine   Morris water maze performance impairment   Increased DARPP-32 phosphorylation  
PLC-beta1 KO Hyperactive Sensorimotor gating deficits Memory impairment and lack of acquisition on hippocampal-dependent fear conditioning task Abnormal social behavior   Clozapine (McOmish) and haloperidol (Koh) rescues sensorimotor deficits
Proline Dehydrogenase (ProDH) KO Reduced open-field behavior, enhanced response to amphetamine and MK801 Diminished PPI     COMT, calcineurin upregulation, reduced D1 and DARPP-32 expression  
Regulator of G-protein Signaling 4 (RGS4) KO   Subtle PPI deficits Impaired working memory      
Retinoic Acid Receptor KO Reduced open field locomotion       Reduced D1R and D2R  
Rictor KO mice   PPI deficit     Reduced phosphorylation of AKT1; reduced dopamine in frontal cortex  
RIM1alpha KO mice Hyperactive in novel setting; enhanced response to MK-801 PPI deficits   Decreased social interaction    
Selectively Bred Low PPI Wistar Rats Reduced motivation PPI deficits, reduced startle habituation Enhanced perseverative behavior Decreased social interaction    
Serine Racemase 1st exon KO Hyperactive   Impaired spatial memory; disrupted order of events representation No social interaction deficit Lack ability to produce D-Serine; altered glutamatergic neurotransmission; abnormal dendritic morphology  
Serine Racemase Targeted Disruption Hyperactive   Impaired spatial memory   Lack ability to produce D-Serine; altered glutamatergic neurotransmission  
SNAP 25 Mutant Mouse Deficit in exploratory behavior PPI deficit   No social interaction deficit    
SNAP 25 overexpression Normal locomotion in open field No PPI deficit Impaired spatial learning in water maze; impaired contextual fear conditioning   Overexpression of SNAP 25 in hippocampus of adult rat  
Sp4 Hypomorphic Mice   PPI deficit Impaired spatial learning; impaired LTP   Hippocampal vacuolization; abnormal development of dentate gyrus; reduced levels of NMDA-NR1 but not NR2A or NR2B  
SREB2 Transgenic Mice   PPI impairments Contextual memory deficits in fear-conditioning task Decreased social interaction Overexpression of SREB2 (GPCR85) in forebrain; Reduced brain weight, increased ventricular volume  
STOP KO Hyperactive; alterations in dopaminergic neurotransmission in the mesolimbic pathway Disrupted PPI Deficits in short term memory and spatial learning; deficits in long-term memory and object recognition Deficits in social learning and recognition Enlarged ventricles; reduced volume of cortex and diencephalon; hypoglutamatergic activity PPI deficit not blocked by clozapine
Synapsin II KO   PPI deficit   Social interaction deficit    
Synapsin III KO mice Hyperactivity in open field PPI deficit Normal spatial learning; object recognition deficit; Abnormal fear conditioning      
SynGAP Heterozygote Hyperactive; increased stereotype in open field Increased acoustic startle response; reduced PPI Apparent working memory impairment in T-maze alternation task; Decreased fear conditioning Impaired social memory; deficit in social interaction   Clozapine improves hyperactivity
Tcf4 Overexpressing Transgenic Mice Normal activity in open field PPI deficit Normal spatial learning in water maze task; impaired fear conditioning      
Trace Amine 1 Receptor KO Enhanced locomotor response to amphetamine Disrupted PPI     Increased psychostimulant-induced DA release  
Transient D2 Receptor Overexpression Hyperactive   Impaired working memory   Overexpression of D2 receptors in striatum  
Transient DISC1 Knockdown in PFC in utero Normal spontaneous locomotion; hypersensitive to methamphetamine PPI deficits in adults but not juveniles Impairment in novel object recognition test   Reduced dopamine concentration in PFC; Reduced parvalbumin-positive interneurons in PFC PPI deficits normalized by clozapine; impairment in novel object recogntion test normalized by clozapine
Type III Nrg1 Targeted Disruption, Heterozygous   PPI deficits Impaired short-term memory   Enlarged ventricles; decreased dendritic spine density on subicular neurons PPI deficits reversed by chronic nicotine treatment
Urokinase Plasminogen Activator Receptor KO (Plaur Mice)     Impaired reversal learning   Reduced parvalbumin-positive interneurons in anterior cingulate and orbitofrontal cortex; reduced levels of HGF/SF Postnatal supplementation with HGF/SF normalizes reversal learning impairment
Vasopressin 1a receptor KO     Decreased social recognition     Phenotype rescued by increase V1a expression in lateral septum
Vasopressin 1b receptor KO Reduced PFC DA Disrupted PPI Impaired novel object recognition Decreased social interest; decreased social novelty preference; Impaired social recognition   Atypical APD improve PPI but not haloperidol
YWHAE Heterozygous KO Normal activity in open field No PPI deficits Mild deficit in spatial working memory, no impairment in reversal learning Normal social interaction 50% reduction of 14-3-3epsilon protein expression  
Printable versionPrintable version Unless otherwise specified, organism is mouse.
Name DA-related behavior Gating Cognitive behavior Social behavior Molecular and/or Morphological Signature Response to APD
Complexin II KO and parietal neurotrauma No interaction effect on open field behavior No interaction effect on PPI; increase in startle amplitude Spatial memory deficit No interaction effect on social interaction Reduced hippocampal volume  
COMT KO and chronic THC exposure Increased hyperactivity in open field in males   No interaction effect on object recognition; increased spatial working memory impairment No interaction effects on social interaction or social novelty preference    
DN-DISC1 and PolyI:C exposure Hypersensitive to MK-801   Impaired object recognition; impaired fear conditioning Decreased social interaction; impaired social recognition PolyI :C exposure on postnatal days 2-6; Decreased GABAergic interneurons in mPFC Clozapine normalized sensitivity to MK-801 as well as cognitive impairment; did not improve social deficits
GAD67 heterozygous KO and prenatal stress         Increased fetal corticosterone level and decreased fetal weight  
mhDISC1 and polyI:C exposure Increased activity in periphery of open field No PPI deficit No interaction effects on novel object recognition; sptial working memory in Y maze, or spatial learning in water maze Lack of preference for sniffing mouse vs inanimate object; normal social novelty preference PolyI:C exposure on gestation day 9; genotype affected cytokine upregulation in response to immune challenge; reduced hippocampal dendritic spine density; attenuated corticosterone response to restraint stress  
Nurr1 heterozygous KO and polyI:C exposure Hyperactive in open field Increased PPI deficit Impaired attentional shifting; no interaction effect on spatial working memory   Decreased accumbal D2 receptors; decreased PFC tyrosine hydroxylase expression; increased PFC COMT expression  
PACAP KO mice and early life social isolation Hyperactive in open field No interaction effect on PPI or startle amplitude   Increased aggression    
Snap-25 heterozygous KO/bdr and prenatal stress No interaction on open field activity PNS/Bdr mice had increased deficit in PPI No interaction effect on short-term memory in Y maze task; no effect on novel object recognition Decreased social interaction and impaired social novelty preference in PNS/Bdr mice   Clozapine improved PPI deficit in PDS/Bdr
Printable versionPrintable version Unless otherwise specified, organism is mouse.
Name DA-related behavior Gating Cognitive behavior Social behavior Molecular and/or Morphological Signature Response to APD
Neonatal Amygdalar Lesion Enhanced amphetamine or apomorphine induced locomotion; increased novelty induced locomotor activity Increased acoustic startle response but impair PPI on animals lesioned on PND 7 but not PND 21; abnormally persistent latent inhibition Impaired place navigation and spatial ability (not found by all studies); impaired spatial alternation and food hoarding Social behaviors diminished in animals lesioned on PND 7 but not 21 but ventral HPC lesions did not affect social behavior Increased lateral ventricular volume; reduced density of D1- and D2-like but not D3-like receptors and increased DA turnover in mesolimbic but not striatal regions; decreased spine density in the prefrontal cortex and nucleus accumbens  
Neonatal NGF-Induced Frontal Cortex Lesion Hyperactivity     Social interaction deficit    
Neonatal Ventral Hippocampal Lesion Enhanced locomotor responses to amphetamine with post-pubertal onset; enhanced meth-amphetamine self-administration Disrupted PPI; prolonged N40 latency Various impairments in learning and memory (including set-shifting and spatial working memory) Impaired social behavior Reduced presynaptic protein and growth factor expression, reduced NMDA receptor expression, impaired DA receptor expression in frontal cortex; impaired maturation of PFC; brain region- and age-specific changes in GABAA receptor expression; reduced PFC spine density; enhanced sensitivity to nicotine; increased prefrontal DA output Locomotor responses blocked by APD, social impairments blocked by clozapine but not haloperidol; clozapine reversed enhanced novelty-induced locomotor activity and rescued neuronal atrophy in the prefrontal cortex and nucleus accumbens
Prefrontal Cortical Lesion Lesion potentiation of amphetamine induced locomotion under high stress conditions only Medial lesions only augment PPI and lesions have no effect on LI        
Printable versionPrintable version
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