2 Neuroscience2.3 Basic techniques in neuroscience
2.3.3 Animal models of psychiatric disease
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Written by Resident Doctor Committee · Published
Validity
An animal model tests a defined process, risk factor or treatment response, not a whole human disorder.
Validity | Question it answers |
|---|---|
Face | Does the behaviour resemble a clinical feature? |
Construct | Is the mechanism relevant? |
Predictive | Does it forecast treatment response? |
Strength in one form of validity does not establish the others.
A read-out is an observed variable, not access to experience: reduced movement may reflect fear or sedation, and reduced sucrose intake may reflect taste or thirst.
Animal behaviour cannot establish hallucinations, guilt or altered identity.
Disease models
Disorder | Model | Findings |
|---|---|---|
Multiple sclerosis | Experimental autoimmune encephalomyelitis (EAE), induced by immunisation against myelin antigens | Immune-mediated inflammatory demyelination |
Mania | ClockΔ19 mutant mouse | Reduced sleep, hyperactivity, low anxiety and heightened reward seeking, reversed by lithium |
Mania | Rapid eye movement (REM) sleep deprivation by the platform (flowerpot) method | Short manic syndrome, prevented by lithium |
Depression | Olfactory bulbectomy in adult rats | Novelty-induced hyperactivity, poor passive avoidance and hypothalamic-pituitary-adrenal (HPA) axis overactivity |
Stress vulnerability | Chronic social defeat | Splits animals into susceptible ones (social avoidance, anhedonia) and resilient ones |
Cuprizone gives toxic demyelination without a primary T-cell attack, unlike EAE.
Restoring CLOCK protein in the ventral tegmental area of ClockΔ19 mice normalises dopamine neurone firing and behaviour.
REM sleep deprivation mirrors sleep loss precipitating mania in people.
Bulbectomy changes reverse only with repeated antidepressant dosing, which gives the model predictive validity.
In social defeat, a dominant resident defeats the animal daily, and the animal is then kept where it can still see and smell that resident. The model suits study of individual vulnerability to stress.
Behavioural tests
Test | Procedure | Measures |
|---|---|---|
Forced swim test | Immobility in a water cylinder is scored | Behavioural despair; the standard rodent depression paradigm for screening antidepressants |
Sucrose preference test | Intake of sweet solution against plain water | Anhedonia in chronic mild stress models of depression, restored by chronic antidepressant treatment |
Elevated plus maze | Drive to explore is set against aversion to open raised arms | Anxiety-like behaviour; benzodiazepines increase open-arm entries and time |
Prepulse inhibition of acoustic startle | A weak sound shortly before a loud one dampens the startle | Sensorimotor gating, reduced in schizophrenia |
Morris water maze | The animal swims to a submerged platform in opaque water using wall cues | Spatial (place) learning and memory, disrupted by hippocampal damage |
Chronic mild stress exposes animals to repeated unpredictable stressors.