Table 1.

Overview on common behavioural paradigms to evaluate rodent models of schizophrenia. Their relevance to specific symptoms, methods and procedures, pros and cons are summarized. Readers may consult the relevant references listed in the last column for detailed descriptions of each test.

Test and behaviour measured	Relevance to schizophernia (SZ) and symptoms to be modelled	Translationability	Advantages	Disadvantages	Critical test parameters	Confounding variables	References
Latent inhibition (LI): measures selective attention conducted in various Pavlovian conditioning paradigms	LI disruption: model of the positive symptoms. LI is disrupted in actively psychotic SZ patients LI persistence: model of the negative symptoms (over-attention)	Human LI tasks substantially differ from animal analogues	Neuroanatomy and neuorchemistry well characterized Multiple paradigms are available	Implementation difficult Additional group required (PE vs. nPE) Not suitable for drug screening	Intensity of US and CS Number of CS pre-exposures Number of CS-US pairings	Effect on associative learning Paradigm-specific effects (anxiety, locomotion, shock sensitivity, etc.)	Weiner 2003; Weiner and Arad 2009
Prepulse inhibition (PPI): measures sensory gating	PPI deficiency is common in SZ patients and considered an endophenotype of the disease Multiple PPI deficiency models of positive and negative symptoms exist	Differences between animal and human PPI tests are minimal	High throughput high translational power Neuroanatomy and neuorchemistry well characterized Extensive data available	Special and expensive equipment required PPI deficits are not unique to SZ but also occur in other neuopsychiatric conditions	Intensity and duration pulse/prepulse stimulus Prepulse-pulse onset asynchrony Background noise level.	Baseline startle reaction Bodyweight	Geyer et al. 2001; Swerdlow et al. 2008
5-choice serial reaction time task (5-CSRTT): measures sustain attention, vigilance and impulsivity	Attention is identified by the MATRICS initiative as a core cognitive domain impaired in SZ 5-CSRTT is the preferred translational test to search for novel drugs that can improve attention in SZ	5-CSRTT parallels human continuous performance tests included in the MATRICS initiative	Neuroanatomy and neuorchemistry well characterized Various measures beyond attention extractable (e.g., impulsivity)	Extensive training and special equipment required Preferably performed in rats Low throughput Not a specific test of attention	Signal duration hold duration (relevant for premature responses) distracters Number of signals	Locomotion Motivation Impulsivity	Chudasama and Robbins 2004; Bari et al. 2008
Working memory (WM): measures the capability to hold information online to solve complex cognitive tasks	WM is identified by the MATRICS initiative as a core cognitive domain impaired in SZ Animal analogues of human WM tests exist with varying degrees of equivalence	Several human WM tasks are available with various degrees of equivalence compared with animals analogues	High translational power Multiple paradigms available Neuroanatomy and neurochemistry well characterized	Extensive training (e.g., operant WM) Labour intensive (e.g., radial arm maze) Special equipment needed (e.g., radial arm maze, operant WM)	Retention interval (delay between trials) Number of items to remember (e.g., arms in radial arm maze) Number of trials per session	Pro-active interference Non-WM strategy (e.g., random search)	Dudchenko 2004; Young et al. 2012
Object and spatial recognition memory: measures familiarity judgement through the animals’ natural tendency to explore new environments/objects	Recognition memory is impaired in SZ Impairment in short-term memory buffer is also implicated in specific working memory (spatial and non-spatial) tasks that are also impaired in SZ	Human analogue in the existing CANTAB neuropsychological tests for humans	Simple and easy to implement Low cost of apparatus construction High throughput Minimal stress to the animals	Several non-specific confound New set-up required for each repeated test Involvement of the hippocampus in object recognition is certain Relative unknown neural basis Cannot be generalized to working memory	Discriminability between objects/environments to be distinguished Retention intervals	Neophobia Motivation to explore Novelty seeking Locomotor activity Sensory abilities	Ennaceur and Delacour 1988; Deacon and Rawlins 2006; Sanderson et al. 2007; Singer et al. 2007
Reversal learning (RL) and attentional set shifting task (ASST): Two problems solving tasks based on two-choice discrimination learning	Problem solving is identified by the MATRICS initiative as a core cognitive domain impaired in SZ ASST is the recommended test for modeling SZ-relevant problem solving in rodents	ASST is a rodent analogue of the CANTAB extra/extra dimensional set task for humans and enjoys high analogy for the Wisconsin Card Sort Task Reward-related touch-screen based RL tasks exist for humans	High translational power (ASST) Simple and cheap equipment (ASST) High throughput (RL)	Labour intensive (ASST) Not suitable for mice (ASST) Low throughput (ASST) Not suitable for drug studies (ASST) Special equipment required (RL)	Type of odours (ASST) Type digging media (ASST) Delay between trials (RL) Number of trials per session (RL)	Motivation Fatigue (ASST) Impulsivity	Birrell and Brown, 2000; Young et al. 2012
Forced swim test (FST): placing animals an inescapable cylinder filled with water is a test of “lost helplessness”	FST is used to model affecting flattening, a negative symptom of SZ, by inducing a state of “dispair” in the animal	No human analogue Diagnosis of flattened affect relies on subjective description of SZ patients	Simple and cheap apparatus High throughput	Manual scoring required Predictive also for anti-depressants	Water depth and temperature	Anxiety Stress Locomotor activity	Porsolt et al. 1978; Cryan et al. 2005
Sucrose preference test: measures the rewarding (hedonic) effect of sucrose consumption	Reduced sucrose preference is a model of anhedonia, a negative symptom of SZ	No human analogue Diagnosis of anhedonia relies on subjective description of SZ patients	Simple and cheap apparatus Simple data analysis No piloting needed High throughput	Preferentially performed in rats False-positive effects of antipsychotics in animals	Concentration of sucrose solution Alternative taste: Saccharine (non-nutritive)	Nutritional value of sucrose Sweetness perception Stress	Pothion et al. 2004
Social interaction test: measures social interaction between an experimental subject an conspecific	Reduced social interaction is a model of social withdrawal, a negative symptom of SZ	No human analogue Diagnosis of social withdrawal relies on subjective description of SZ patient	High throughput Simple data analysis Suitable for drug testing	Predictive also for anxiolitics and anti-autistic drugs High group sizes required Testing female subjects problematic	Housing condition (individual vs. grouped housing) Habituation to test environment Lighting/brightness	Anxiety Locomotor activity Stress	Crawley 2007a
Open field test: measures spontaneous locomotor activity in an open field arena	Psychostimulant-induced hyper-locomotion models the hypersensitivity of SZ patients to psychostimulants Amphetamine is used to model the positive symptoms Phencyclidine is used to model the negative symptoms	Almost no human open fied data	Simple and cheap equipment High throughput Simple data analysis Suitable for drug testomg	No face validity (SZ patients are hypoactive if anything)	Size and shape of open field Lighting/brightness Duration of test period	Anxiety Baseline activity (when testing drugs) Habituation/Dishabituation	Henry et al. 2011