Animal models

Question 1

What is face validity?

Answer 1

Does the model capture some or all of the symptoms of the human disease?

Question 2

What is construct validity?

Answer 2

Do the pathophysiology and aetiology mirror the human disease?

Question 3

What is predictive validity?

Answer 3

Does the model predict which treatments will be effective in human patients?

Question 4

What is the aim of using animal models?

Answer 4

• 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

Question 5

What is the aim of using behavioural tests?

Answer 5

• Attempt to assess the impact of a treatment on disease symptoms
• Often focus on predictive validity

Question 6

What are some examples of animal models of depression?

Answer 6

Learned helplessness, unpredictable chronic mild stress, maternal separation/ELS, social defeat, olfactory bulbectomy, aberrant glutamatergic signalling

Question 7

How can despair be tested in animal models of depression?

Answer 7

• Forced swimming test
• Tail suspension

Question 8

How can anhedonia be tested in animal models of depression?

Answer 8

• Sucrose preference test
• Reduced intra-cranial self-stimulation

Question 9

How can lack of motivation be tested in animal models of depression?

Answer 9

Decreased grooming and decreased nest building

Question 10

Describe the forced swimming test

Answer 10

• 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

Question 11

Describe the tail suspension test

Answer 11

• 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

Question 12

Describe the sucrose preference test

Answer 12

• 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

Question 13

Describe the intra-cranial self-stimulation test

Answer 13

• 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

Question 14

Describe the light/dark box test used to test for anxiety

Answer 14

• 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

Question 15

Describe the open field test

Answer 15

• 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

Question 16

Describe the elevated plus maze

Answer 16

• 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

Question 17

Describe novelty-induced hypophagia

Answer 17

Reduction in feeding in response to anxiety

Question 18

Adverse events in childhood can make people vulnerable to depression. What is an examples of ELS used in animal models?

Answer 18

• 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

Question 19

Describe olfactory bulbectomy as an animal model of depression

Answer 19

• 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

Question 20

Describe the genetic models of HPA axis hyperactivity as an animal model of depression

Answer 20

• 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

Question 21

What can stress and AMPA receptors do to synaptic strength respectively?

Answer 21

• Stress - decreases in synaptic strength and spine loss
• AMPAR - increases in synaptic strength and synaptogenesis

Question 22

What role in medicine has ketamine been recently discovered to possess?

Answer 22

• 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

Question 23

Describe the antidepressant action of tianeptine

Answer 23

• 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

Question 24

Describe the role of prefrontal cortex activity in depression

Answer 24

• Connections between the medial prefrontal cortex mediate associations between environmental stimuli and reward
• Prefrontal activity and spine density is reduced in depression

Question 25

Describe the role of the hippocampus in depression

Answer 25

• Depression involves underactivity in the median raphe nucleus to hippocampus projection during aversive events
• This underactivity results in a reduction in the inhibition of hippocampal activity via 5HT1A receptors
• The hippocampus is therefore overactive during aversive events and the consolidation of aversive memories