| Genetic preparations |
| NMDA NR1 receptor hypomorph (Mohn et al, 1999; Fradley et al, 2005) |
Enhanced response to amphetamine |
Disrupted PPI |
|
Impaired social interaction |
95% reduction in NRI expression |
Behaviors improved by APD |
| STOP KO (Fradley et al, 2005) |
Hyperactive |
Disrupted PPI |
|
|
|
PPI deficit not blocked by clozapine |
| GluR-A receptor KO (Bannerman et al, 2004) |
Hyperactive |
|
Disrupted spatial working memory |
|
|
Anxiety prone |
| GABAAα3 receptor KO (Yee et al, 2005) |
Spontaneous locomotor activity slightly increased but not after amphetamine |
Disrupted PPI |
|
|
|
PPI defect improved by haloperidol Rx |
| Dishevelled 1 KO (Lijam et al, 1997) |
|
Disrupted PPI |
|
Impaired social interaction |
|
|
| Calcineurin Aγ KO (Miyakawa et al, 2003) |
Enhanced response to amphetamine |
Disrupted PPI and latent inhibition |
Decreased working memory |
Impaired social interaction |
Inducible KO |
|
| Catecholamine O-methyl transferase (COMT) KO (Gogos et al, 1998; Huotari et al, 2004) |
No potentiation of amphetamine-induced locomotion |
|
|
|
Increased DOPAC, D1 and D2 unchanged |
Increased anxiety and aggression |
| Heterozygous Reeler mouse (Ballmaier et al, 2002; Costa et al, 2002; Podhorna and Didriksen, 2004) Kruger et al, 2006
|
Enhanced mesolimbic dopamine |
|
Decreased working memory; no decrease in prefrontal cortex dependent task |
Impaired social interaction |
Reduced GAD 67, increased DNA methylation |
|
| Neurexophillin 3 KO (Beglopoulos et al, 2005) |
Reduced rotorod performance |
Disrupted PPI but increased startle response |
|
|
Expressed in Cajal-Retzius cells |
|
| Neuregulin 1 hypomorph (Stefansson et al, 2002) |
Hyperactive in open field test |
Disrupted PPI |
|
|
Reduced NMDA receptor activity |
Open field behavior reversed by clozapine but not PPI |
| DISC1 KO (Hikida et al, 2007; Duan et al, 2007; Pletnikov et al, 2007; Clapcote et al, 2007) |
Enhanced locomotor activity |
Disrupted PPI; Decreased latent inhibition |
|
Impaired social interaction |
Decreased cortical parvalbumin-containing cells, accelerated neurogenesis with aberrant connectivity |
|
| ErbB4 KO (Golub et al, 2004) |
Reduced spontaneous activity |
|
Reduced Morris water maze learning |
|
|
|
| nPAS 1/3 KO (Erbel-Sieler et al, 2004; Pieper et al, 2005) |
Enhanced open field locomotion |
Disrupted PPI |
Decreased social recognition |
|
Reduced reelin interneurons |
|
| Heterozygous Nurr1 KO (Rojas et al, 2007) |
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 |
| Retinoic acid receptor KO (Krezel et al, 1998) |
Reduced open field locomotion |
|
|
|
Reduced D1R & D2R |
|
| Vasopressin 1a receptor KO (Bielsky et al, 2005) |
|
|
Decreased social recognition |
|
|
Phenotype rescued by increase V1a expression in lateral septum |
| Vasopressin 1b receptor KO (Wersinger et al, 2002) |
Reduced PFC DA |
Disrupted PPI |
Impaired social recognition |
|
|
Atypical APD improve PPI but not haloperidol |
| Oxytocin and oxytocin receptor KO (Ferguson et al, 2001; Takayanagi et al, 2005) |
|
|
|
Impaired social discrimination |
|
More aggressive |
| Dopamine Transporter KO (Trinh et al, 2003; Rodriguiz et al, 2004) |
Increased DA and decreased D1R, D2R, Hyperactive |
Disrupted PPI |
|
Impaired social behavior |
|
More aggressive |
| Regulator of G-protein signalling 4 (RGS4) KO (Grillet et al, 2005) |
|
Subtle PPI deficits |
Impaired working memory |
|
|
|
| GDI1 knockout (DAdamo et al, 2002) |
|
|
Impaired short-term memory |
Diminished social behavior |
|
Less aggression |
| Cannabinoid receptor 1 (CB1) KO (Haller et al, 2005) |
Decreased PCP-induced locomotion |
|
|
No effect on social interaction |
|
|
| Complexin I KO (Glynn et al, 2005) |
Decreased amphetamine-induced locomotion |
|
|
|
|
|
| Complexin II KO (Yamauchi et al, 2005) |
|
|
Decreased LTP; reduced morris water maze performance only after stress |
|
|
|
| Homer1a KO (Szumlinski et al, 2005) |
Enhanced locomotor behavior to MK-801 and methamphet-amine |
Disrupted PPI |
Decreased radial arm maze performance |
|
Decreased glutamate release in PFC following cocaine Rx |
|
| Glycine transporter KO (Tsai et al, 2004) |
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 |
|
| GSK-3 beta knockout (Amar et al, 2004) |
|
Disrupted PPI correlates with enzyme activity |
|
|
|
|
| mGluR1 knockout (Brody et al, 2003) |
|
Disrupted PPI |
|
|
|
Not reversed by raclopride |
| mGluR5 knockout (Kinney et al, 2003; Brody et al, 2004) |
|
Disrupted PPI |
|
|
|
APD not effective |
| Proline Dehydrogenase (ProDH) KO (Gogos et al, 1999; Paterlini et al, 2005) |
Reduced open-field behavior, enhanced response to amphetamine and MK801 |
Diminished PPI |
|
|
COMT, calcineurin upregulation, reduced D1 and DARPP-32 expression, |
|
| Chromosome 22 deletion (Paylor et al, 2001) |
|
Disrupted PPI |
Impaired cognitive function |
|
|
|
| GAP-43 KO (Metz and Schwab, 2004) |
Hyperactive in open field, reduced anxiety |
Disrupted PPI |
|
|
|
|
| NCAM-180 KO (Wood et al, 1998) |
|
Disrupted PPI, no changes induced by apomorphine Rx |
|
|
|
Increase lateral ventricle size |
| Phosphodiesterase 1B KO (Reed et al, 2002) |
Enhanced behavioral response to methamphetamine |
|
Morris water maze performance impairment |
|
Increased DARPP-32 phosphorylation |
|
| Beta-arrestin 2 KO (Beaulieu et al, 2005) |
Decreased locomotor response to amphetamine |
|
|
|
Normal DARRPP-32 phosphorylation after amphetamine |
|
| Trace Amine 1 Receptor KO Wolinsky et al, 2006
|
Enhanced locomotor response to amphetamine |
Disrupted PPI |
|
|
Increased psychostimulant-induced DA release |
|
| Insulin Receptor KO Zhao et al, 2006
|
|
Decreased startle amplitude |
|
|
Decreased insulin receptor and Akt signaling; reduced phosphorylated GSK-3 |
Clozapine alleviates insulin resistance |
| Corticotropin releasing factor (CRF) overexpression (Dirks et al, 2003) |
|
Disrupted PPI |
|
|
|
|
| DBA/2 Mouse (Stevens et al, 1998) |
|
Disrupted N40 gating & PPI |
|
|
Phenotype reversed by α7-nicotinic receptor agonist |
|
| 129S6/SvEv Mouse Koike et al, 2006
|
|
|
Working memory deficit |
|
DISC1 mutation |
|
| Apomorphine Susceptible Rat (Ellenbroek and Cools, 2002) |
Enhanced locomotor response to novel open field |
Disrupted PPI and diminished latent inhibition |
|
|
|
|
| Developmental preparations |
| Rat prenatal variable stress (Kinnunen et al, 2003; Koenig et al, 2005) |
Increased response to amphetamine and PCP with post-pubertal onset |
Disrupted PPI & N40 |
Impaired object and social recognition |
Impaired social interaction present in adolescent and adult rats; reversal by oxytocin; no effect of cross-fostering |
NMDA, GABAergic and presynaptic protein dysregulation |
Stress applied during period of fetal brain development that overlaps with period identified in human epidemiological studies |
| Mouse Prenatal Viral infections (Fatemi et al, 1999, 2005; Shi et al, 2003) |
Decreased open-field exploration; |
Impaired PPI |
|
Impaired social interaction |
Reduced reelin expression in cortex layer 1; reduced cortical thickness; increased pyramidal cell density |
Clozapine and chlorpromazine increase PPI—hyper-reversal of PPI deficit |
| Rodent Prenatal PolyI:C Challenge (GD 9) (Borrell et al, 2002; Shi et al, 2003; Meyer et al, 2005, 2006) |
No change in total distance traveled in open field but reduced center exploration; increased response to amphetamine |
Disrupted PPI; latent inhibition changes appear after puberty; no effect of cross-fostering |
Reduced escape latency in Morris water maze |
|
Amphetamine-induced DA release increased; increased hippocampal pyknotic cells |
Latent inhibition defect reversed by clozapine and haloperidol |
| Rat Borna disease virus infection (Solbrig et al, 2000; Pletnikov et al, 2002; Hans et al, 2004) |
Enhanced novelty-induced locomotor activity in Fisher rats; enhanced amphetamine-induced locomotion |
Disrupted PPI in Fisher rats |
|
|
Impairs BDNF synaptogenesis; prefrontal cortex thinning |
|
| Rat neonatal ventral hippocampal lesion (Lipska, 2004) |
Increased response to amphetamine |
Disrupted PPI |
Decreased working memory |
Impaired social interaction |
Reduced presynaptic protein expression |
Deficits improved by atypical APD |
| Rat antimitotic agent—MAM or AraC (Elmer et al, 2004; Flagstad et al, 2004; Gourevitch et al, 2004) Moore et al, 2006; Featherstone et al, 2007
|
Enhanced response to amphetamine |
Disrupted PPI |
Learning deficits in Morris water maze and object recognition; no change in 5-choice serial reaction time task |
Decreased social interaction |
Decreased brain, hippocampus weight; increased neuron density in prefrontal cortex; enhanced NAc DA release to amphetamine |
|
| Rat maternal malnutrition (Palmer et al, 2004) |
|
Disrupted PPI that becomes apparent on PND 56 but not PND 35 |
|
|
|
Striatal NMDA receptor-binding increased without DA change |
| Rat prenatal vitamin D insufficiency (Kesby et al, 2006; Eyles et al, 2006) |
Enhanced response to MK-801 |
No disruption in PPI |
|
|
|
Stress reactivity unchanged |
| Rat placental insufficiency/birth insults (Boksa, 2004) |
Enhanced response to amphetamine |
|
|
|
Reduced DA release in PFC, increased DAT in NAc (basal), decreased DA receptor expression |
|
| Rat isolation rearing (Geyer et al, 1993; Varty and Geyer, 1998; Heidbreder et al, 2000; Weiss et al, 2000) |
Strain dependent enhancement of amphetamine locomotion |
Disrupted PPI that is strain dependent |
|
|
Increased amphetamine-induced DA release |
Raclopride reversed PPI deficit |
| Monkey fetal irradiation (Selemon et al, 2005) |
|
|
|
|
|
Mid-gestational irradiation decreases both gray and white matter in frontal cortex |
| Rat 24 h maternal deprivation on postnatal day 9 (Ellenbroek et al, 1998) |
|
Disrupted PPI, effect develops after puberty |
|
|
|
Haloperidol reverses PPI deficit |
| Drug-induced preparations |
| Acute NMDA receptor antagonist Rx (MK801, PCP, ketamine) (Jentsch and Roth, 1999) |
Increases locomotor activity |
|
Decreased working memory |
Impaired social interaction |
|
Enhanced locomotor responses blocked by APD |
| Chronic NMDA receptor antagonist Rx (MK801, PCP, ketamine) (Jentsch and Roth, 1999; Sams-Dodd, 1999; Lee et al, 2005) |
Enhanced locomotor response to psychomotor stimulants |
Disrupted PPI |
Decreased working memory |
Impaired social interaction |
Diminished expression of NMDA receptor coupled IEG, Homer 1a |
Enhanced locomotor responses blocked by APD, social behavior and PPI impairments blocked by clozapine but not haloperidol |
| Basolateral Amygdala Picrotoxin Infusion—Rat (Berretta et al, 2001; Gisabella et al, 2005) |
|
|
|
|
|
GABA antagonism in BLA decreases GAD67 in HPC; GABA antagonism in BLA increases HPC LTP |
| Lesion models |
| Neonatal ventral hippocampal lesion (Lipska and Weinberger, 2000; Lipska, 2004) |
Enhanced locomotor responses to amphetamine with post-pubertal onset |
Disrupted PPI |
Various impairments in learning and memory |
Impaired social behavior |
Reduced presynaptic protein and growth factor expression, reduced NMDA receptor expression, impaired DA receptor expression in frontal cortex |
Locomotor responses blocked by APD, social impairments blocked by clozapine but not haloperidol |
| Amygdalar Lesion (Hanlon and Sutherland, 2000; Daenen et al, 2002, 2003; Weiner, 2003) |
Enhanced amphetamine or apomorphine-induced locomotion |
Increase acoustic startle response but impair PPI on animals lesioned on PND 7 but not PND 21; abnormally persistent latent inhibition |
Impaired place navigation & spatial ability |
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 |
|
| Prefrontal Cortical Lesion (Miner et al, 1997; Wilkinson et al, 1997; Lipska et al, 1998; Lacroix et al, 2000) |
Lesion potentiation of amphetamine induced locomotion under high stress conditions only |
Medial lesions only augment PPI & lesions have no effect on LI |
|
|
|
|
