Table 1.

Comparative overview of the changes in basal and psychostimulant-induced locomotor activity in an open-field arena; sensorimotor gating; learning and memory; social interaction with a conspecific, structural and neurochemical changes in cortical and hippocampal areas and the reversal of these changes with antipsychotic and related drugs for selected animal models of schizophrenia

Animal model	Basal- and drug- induced locomotor activity	Sensorimotor gating	Cognition	Social interaction	Structure and neurochemistry	Antipsychotic reversal
Gestational MAM (GD17) (Moore et al., 2006; Lodge et al., 2009)	Spontaneous hyperactivity in novel arena emerging at puberty. Enhanced amphetamine- and NMDA antagonist-induced locomotion.	Deficit in PPI appears at puberty.	Normal acquisition, but impaired re-learning in the Morris water maze; impaired extra-dimensional shift in attentional set-shifting task	Reduced total social interaction appears prior to puberty.	Reduced PFc and hippocampal size, enlarged ventricals, reduced hippocampal soma size and neuropil; enhanced nAcc DA release; spontaneously hyperactive VTA DA neurones; decreased PFc parvalbumin GABA interneurones	No pharmacological reversal of behaviour attempted. CLZ does not reverse change in BDNF.
Post-weaning social isolation (Lapiz et al., 2003; Fone and Porkess, 2008)	Hyperactivity in a novel arena appearing 2–3 weeks after commencing isolation; hyper-responsivity to amphetamine and cocaine together with increased nAcc DA release	Persistent, but strain-dependent reduction in PPI to acoustic startle appearing about 6 weeks after isolation	Deficit in novel object recognition; no effect on acquisition of spatial learning by impaired reversal learning in water maze, extra-dimensional shift in the attentional set-shifting task and fear-motivated conditioned emotional response	Increased aggression and increase in total social interaction	Reduced PFc volume; reduced dendritic spine density, cytoskeletal alteration and loss of parvalbumin-containing interneurones and reelin in the hippocampus; reduced PFc D1 binding, no change in striatal D2 density, but increased proportion of striatal D2High; increased spontaneously active VTA DA neurones	PPI reversed by atypical antipsychotics, D2 antagonists, α7-nicotinic agonists; novel object discrimination impairment reversed by 5-HT6 antagonists and mGluR2/3 agonist
Amphetamine models (Featherstone et al., 2007a; Featherstone et al., 2008; Sarter et al., 2009)	Sensitization of locomotor response to amphetamine	Persistent deficit in PPI dependent on dosage regimen	Deficits in attention and the attentional set-shifting task; hippocampal-dependent memory unimpaired	No reduction in social interaction	Enhanced mesolimbic DA response; altered ACh function in PFc	Locomotor sensitization blocked by CLZ and HLP; moderate attenuation of attention impairment by CLZ and HLP
PCP models (Jentsch and Roth, 1999; Phillips et al., 2001; Mouri et al., 2007; Neill et al., 2010)	Sensitization of locomotor response to PCP; hyper-responsive locomotor response to amphetamine and mild stress	No sustained deficit in PPI	Deficits in novel object recognition, attentional set shifting and T-maze delayed alternation	Reduced frequency and duration of primate social behaviour	Reduced basal and stress-induced PFc DA and glutamate release; decreased synaptic spines on Fc neurones and cortical and hippocampal parvalbumin-positive neurones	Deficits in reversal learning reversed by atypical antipsychotics but not HLP; locomotor sensitization attenuated by CLZ and HLP
Neonatal ventral hippocampal lesion (Lipska, 2004; Tseng et al., 2009)	Locomotor hyper-responsivity to stress, amphetamine and NMDA receptor antagonists; enhanced apomorphine-induced stereotypy	Adult onset deficit in PPI	Impaired acquisition of T-maze delayed alternation and water maze; impaired radial arm maze choice accuracy; selective deficit in extra-dimensional shift and reversal in the attentional set-shifting task	Deficits in social interaction with increased aggression at all developmental ages	Unaltered basal nAcc DA release, but enhanced response to stress or amphetamine; reduced mPFc NAA levels and GAD67 mRNA expression	Amphetamine-induced hyperactivity reversed by acute or chronic antipsychotic injection; social interaction deficit not reversed by CLZ
DISC-1 knock-out (Jaaro-Peled, 2009)	Hyperactivity seen in L100P, CaMK-ΔC mutants, but not in others; no data available regarding psychostimulant-induced locomotor activity to date	Deficits in PPI seen in some (e.g. constitutive CaMK-ΔC, L100P, Q31L), but not all mutants (e.g. inducible CaMK-ΔC, Δ25 bp); PPI not tested in CaMK cc or BAC ΔC mutants	Impaired T-maze performance seen in most strains; impaired spatial working memory only seen in female CaMK-ΔC inducible mutants	Reductions in social activity seen in some strains (e.g. Q31L) and some CaMK- ΔC transgenics	Reduced brain volume in most strains; enlarged lateral ventricles, reduced hippocampal and PFc dendritic density, structure and complexity in some strains; reduced hippocampal parvalbumin immunoreactivity in some, but not all mutants	PPI deficits in L100P mice reversed by HLP and CLZ
Neuregulin1 and ErbB4 knock-out (Harrison and Law, 2006a; Mei and Xiong, 2008)	Most, but not all, neuregulin and ErbB4 mutants show spontaneous locomotor hyperactivity, but inconsistent responses to psychostimulants	PPI deficits seen in most neuregulin mutants reviewed; ErbB4 mutants show normal PPI	Impaired contextual fear and mismatched negativity performance in some mutants	Some deficits in social interaction, increased aggression and reduced responses to social novelty	Increased lateral ventricles and reduced hippocampal spine density; reduction in functional forebrain NMDA receptors	Spontaneous and psychostimulant-induced locomotor hyperactivity reversed by CLZ in Nrg1(ΔTM)+/− and Nrg1(BACE)−/− mutants
Dysbindin knock-out (Karlsgodt et al., 2011; Papaleo et al., 2010)	Spontaneous locomotor hyperactivity and hyper-responsivity to amphetamine challenge	Increased PPI and startle response shown to be reversed by quinpirole, but not eticlopride	Increased acquisition of T-maze task; impaired spatial reference memory and novel object recognition performance	Reduced social contact during social interaction task	Hyperexcitability of PFc pyramidal neurones; altered synaptic structure and formation; elevated HVA/DA ratio in cortico-limbic regions	No data on antipsychotic reversal
Reelin knock-out (Krueger et al., 2006; Tueting et al., 2006)	Reduced locomotion in an open field; enhanced response to methamphetamine	Variable PPI responses, highly dependent on strain, environment and testing protocol	Few memory deficits reported; normal reversal learning and inhibitory control, normal MWM performance; some learning deficits in acquisition of operant tasks	Some modulation of social activity in novelty and/or interaction tasks	Increased neuronal packing and decreased dendritic spine density in PFc and hippocampal neurones	Normalization of reduced spontaneous activity by OLZ

Note that some of the tasks as discussed in the review are thought to have translational relevance to particular symptom domains affected in schizophrenia. However, other experimental observations, such as drug-induced changes, do not directly relate to core symptoms, but are used as an index to test dysfunction of the neuronal pathways that are thought to contribute to schizophrenia.

5-HT₆, 5-hydroxytryptamine₆ receptor; BDNF, brain-derived neurotrophic factor; CLZ, clozapine; D₁, dopamine D₁ receptor; D₂, dopamine D₂ receptor; DA, dopamine; DISC-1, disrupted-in-schizophrenia 1; GAD₆₇, glutamic acid decarboxylase enzyme 67 kDa isoform; HLP, haloperidol; MWM, Morris water maze; PFc, prefrontal cortex; PPI, prepulse inhibition of acoustic startle; NAA, N-acetylaspartic acid; nAcc, nucleus accumbens; NMDA, N-methyl-d-aspartic acid; OLZ, olanzapine; PCP, phencyclidine; VTA, ventral tegmental area.