Animal models Flashcards
What is face validity?
Does the model capture some or all of the symptoms of the human disease?
What is construct validity?
Do the pathophysiology and aetiology mirror the human disease?
What is predictive validity?
Does the model predict which treatments will be effective in human patients?
What is the aim of using animal models?
- Attempt to reproduce a disease state in an animal
- Changes in physiology and behaviour observed
- May only attempt to model one aspect of the disease pathology
- Often focus on construct validity
What is the aim of using behavioural tests?
- Attempt to assess the impact of a treatment on disease symptoms
- Often focus on predictive validity
What are some examples of animal models of depression?
Learned helplessness, unpredictable chronic mild stress, maternal separation/ELS, social defeat, olfactory bulbectomy, aberrant glutamatergic signalling
How can despair be tested in animal models of depression?
- Forced swimming test
- Tail suspension
How can anhedonia be tested in animal models of depression?
- Sucrose preference test
- Reduced intra-cranial self-stimulation
How can lack of motivation be tested in animal models of depression?
Decreased grooming and decreased nest building
Describe the forced swimming test
- Mice or rats are placed in glass cylinders and heir behaviour is scored
- After a time animals give up swimming/attempting to escape and remain immobile
- Antidepressants increase the time before immobility
Describe the tail suspension test
- Conceptually similar to forced swimming test
- After a time, animal give up struggling and attempting to escape
- Antidepressants increase time spent engaging in escape behaviours
Describe the sucrose preference test
- Rodents are presented with a choice between sucrose solution or water
- The amount of each consumed is measured
- Models of depression may cause a reduced preference for sucrose, a measure of anhedonia
Describe the intra-cranial self-stimulation test
- Rodents with chronically implanted hypothalamic electrodes find self-stimulation rewarding and will work for reward
- A reduction in self-stimulation provides a measure of reduced interest in rewarding stimuli
Describe the light/dark box test used to test for anxiety
- Number of entries and time spent in the light area recorded
- Pits the natural desire to explore against the anxiety associated with bright, open areas
Describe the open field test
- Animals are allowed to explore a brightly lit open field arena
- Time in the centre versus the periphery of the arena is recorded
- Anxious animals stick to the sides and avoid the centre
Describe the elevated plus maze
- Animals are tracked as they explore an elevated maze with two enclosed arms and two open arms
- Anxious rodents spend less time in the open arms and more time in the enclosed arms
Describe novelty-induced hypophagia
Reduction in feeding in response to anxiety
Adverse events in childhood can make people vulnerable to depression. What is an examples of ELS used in animal models?
- Maternal separation/deprivation
- Pups are separated from the dam for 1-24 hours per day during the first 2 postnatal weeks
- Results in increased anxiety and depression like behaviour
Describe olfactory bulbectomy as an animal model of depression
- Removal of the olfactory bulbs in rodents results in depressive symptoms and a range of physiological changes
- The reasons for this are poorly understood but bulbectomy may cause chronic stress owing to sensory deprivation/hippocampal dysfunction
Describe the genetic models of HPA axis hyperactivity as an animal model of depression
- Evidence for HPA-axis hyperactivity and elevated cortisol levels in depressed patients
- Reduced glucocorticoid receptor expression may cause deficient feedback, leading to increased HPA activity
What can stress and AMPA receptors do to synaptic strength respectively?
- Stress - decreases in synaptic strength and spine loss
- AMPAR - increases in synaptic strength and synaptogenesis
What role in medicine has ketamine been recently discovered to possess?
- Ketamine is an NMDAR antagonist that was recently discovered to have rapid-onset antidepressant properties
- A metabolite of ketamine, HNK, enhances AMPA receptor mediated transmission but is inactive at the NMDAR. It is necessary and sufficient for ketamines antidepressant properties
Describe the antidepressant action of tianeptine
- Enhances place recognition memory in mice
- Enhances hippocampal AMPAR mediated synaptic transmission and LTP
- Tianeptine is a mu and delta opioid receptor agonist - its actions on opioid receptors may underlie its AMPA modulating properties
Describe the role of prefrontal cortex activity in depression
- Connections between the medial prefrontal cortex mediate associations between environmental stimuli and reward
- Prefrontal activity and spine density is reduced in depression
