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How can a rat, which cannot report feeling guilty or hearing voices, ever model depression or schizophreniaA long-term mental illness involving episodes of psychosis such as hallucinations and delusions.Read more →? It cannot model the whole disorder, and that limit is the starting point for understanding animal models: each one is judged not on whether it recreates the human illness wholesale, but on how well it satisfies three separate kinds of validityHow well a measurement or test actually measures the thing it is meant to measure.Read more →. For example, imagine a mouse placed in water it cannot escape from, which after some minutes stops swimming and floats passively (the forced swim test): that immobility resembles behavioural despair on the surface, and, usefully, it is reduced by antidepressant treatment much as human low mood responds to it — but the mouse is not reporting sadness, guilt or hopelessness, so the model captures a narrow behavioural proxy, not the subjective experience of depression itself. In practice, this means reading about any animal model requires asking which specific validity claim it is making, rather than treating 'it's an animal model of X' as a single, all-or-nothing statement.

Three types of validityHow well a measurement or test actually measures the thing it is meant to measure.Read more → are used to judge an animal model. Face validity asks whether the model's observable features resemble the surface features of the human disorder (for example, reduced movement resembling psychomotorRelating to the link between mental state and physical movement, such as being visibly slowed down or agitated.Read more → slowing). Construct validity asks whether the model shares the same underlying biological or psychological mechanism thought to produce the human disorder (for example, early-life adversity in a developmental model mirroring early-life risk factors for depression in humans). Predictive validity asks whether the model responds to treatments the same way the human disorder does — improving with drugs that work clinically and not with drugs that do not. Named depression models include the forced swim test and learned helplessness (inducing inescapable stress, then measuring passive, 'given-up' behaviour such as immobility or failure to escape when escape later becomes possible), both of which have reasonable predictive validity, since the passive behaviour is reduced by antidepressant treatment. The chronic mild stress model instead exposes an animal to a prolonged series of mild, unpredictable stressors and measures anhedoniaThe loss of the ability to feel pleasure from things that used to be enjoyable.Read more → (reduced pleasure-seeking, operationalised as reduced preference for sucrose-sweetened water), a state that normalises only with chronic, not acute, antidepressant treatment — closely mirroring the delayed onset of clinical antidepressant response and giving the model good face and predictive validity (Willner, 1997). For schizophreniaA long-term mental illness involving episodes of psychosis such as hallucinations and delusions.Read more →, amphetamine-induced hyperlocomotion (increased movement following a dopamine-releasing stimulant) models the dopamine-hyperactivity component of the disorder and is reversed by antipsychotics, giving it reasonable predictive validity for positive symptoms (hallucinationsSeeing, hearing, or otherwise sensing things that are not really there.Read more →, delusionsA fixed false belief, held with total conviction, that is not shared by the person's culture and is not changed by evidence against it.Read more →) but poor face validity for negative symptoms (apathy, blunted emotion, social withdrawal) or cognitive impairment. NMDA-receptor antagonistA drug that blocks a receptor, stopping it from being activated.Read more → models (using drugs such as ketamine, phencyclidine (PCP), or MK-801 to block glutamate signalling at the NMDA receptorA glutamate receptor in the brain involved in learning and memory, and a target of drugs like ketamine and memantine.Read more →) better reproduce negative-symptom-like social withdrawal and cognitive deficits alongside hyperlocomotion, reflecting the glutamate hypothesis of schizophrenia as a complement to the older dopamine hypothesis (Javitt & Zukin, 1991).

A question describing a specific animal-model finding (an immobility test reversed by antidepressants, an anhedoniaThe loss of the ability to feel pleasure from things that used to be enjoyable.Read more → measure that only improves after weeks of dosing, a stimulant-induced behaviour reversed by antipsychotics, or an NMDA-antagonistA drug that blocks a receptor, stopping it from being activated.Read more →-induced withdrawal/cognitive deficit) and asking which type of validityHow well a measurement or test actually measures the thing it is meant to measure.Read more → the finding demonstrates, or which named model is being described.

• Face validity vs construct validity, face validityHow well a measurement or test actually measures the thing it is meant to measure.Read more → asks whether the model looks like the disorder on the surface, whereas construct validity asks whether it shares the same underlying mechanism, and a model can have one without the other.
• Face/construct validityHow well a measurement or test actually measures the thing it is meant to measure.Read more → vs predictive validity: predictive validity is specifically about whether the model responds to treatment the way the human disorder does, unlike face or construct validity, which say nothing about treatment response on their own.
• Forced swim test/learned helplessness vs chronic mild stress: both model depression-like behaviour, but forced swim/learned helplessness measures acute passive behaviour reversed by antidepressants of any duration, whereas chronic mild stress measures anhedoniaThe loss of the ability to feel pleasure from things that used to be enjoyable.Read more → that reverses only with CHRONIC antidepressant dosing, more closely tracking the clinical delay to response.
• Amphetamine hyperlocomotion vs NMDA-receptor antagonistA drug that blocks a receptor, stopping it from being activated.Read more → models: amphetamine models the dopamine-driven, antipsychotic-reversible positive-symptom picture of schizophreniaA long-term mental illness involving episodes of psychosis such as hallucinations and delusions.Read more →, whereas NMDA-receptor antagonists (ketamine, PCP, MK-801) additionally reproduce negative-symptom-like and cognitive deficits, reflecting the glutamate rather than the dopamine mechanism.

• Treating 'this is a good animal model' as a single, all-or-nothing judgement rather than asking which of face, construct, or predictive validityHow well a measurement or test actually measures the thing it is meant to measure.Read more → is actually being claimed.
• Assuming amphetamine-induced hyperlocomotion models the full syndrome of schizophreniaA long-term mental illness involving episodes of psychosis such as hallucinations and delusions.Read more →, when it mainly captures the dopamine-driven positive-symptom picture and has poor face validityHow well a measurement or test actually measures the thing it is meant to measure.Read more → for negative or cognitive symptoms.
• Confusing acute antidepressant reversal (forced swim/learned helplessness) with the chronic-dosing requirement that gives the chronic mild stress model its distinctive predictive-validityHow well a measurement or test actually measures the thing it is meant to measure.Read more → strength — the two depression models are not interchangeable evidence for the same point.

When a stem describes an animal-model finding, first identify which validityHow well a measurement or test actually measures the thing it is meant to measure.Read more → type it is illustrating: surface resemblance to the disorder (face), shared underlying mechanism (construct), or appropriate treatment response (predictive). Then match the described behaviour to the specific named model (forced swim/learned helplessness, chronic mild stress, amphetamine hyperlocomotion, or NMDA-receptor antagonistA drug that blocks a receptor, stopping it from being activated.Read more →) rather than answering from the disorder name alone, since different models within the same disorder target different symptom domains.