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Translational psychiatry and neurology > Animal models > Flashcards

Flashcards in Animal models Deck (25)
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1
Q

What is face validity?

A

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

2
Q

What is construct validity?

A

Do the pathophysiology and aetiology mirror the human disease?

3
Q

What is predictive validity?

A

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

4
Q

What is the aim of using animal models?

A
  • 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
5
Q

What is the aim of using behavioural tests?

A
  • Attempt to assess the impact of a treatment on disease symptoms
  • Often focus on predictive validity
6
Q

What are some examples of animal models of depression?

A

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

7
Q

How can despair be tested in animal models of depression?

A
  • Forced swimming test
  • Tail suspension
8
Q

How can anhedonia be tested in animal models of depression?

A
  • Sucrose preference test
  • Reduced intra-cranial self-stimulation
9
Q

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

A

Decreased grooming and decreased nest building

10
Q

Describe the forced swimming test

A
  • 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
11
Q

Describe the tail suspension test

A
  • 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
12
Q

Describe the sucrose preference test

A
  • 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
13
Q

Describe the intra-cranial self-stimulation test

A
  • 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
14
Q

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

A
  • 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
15
Q

Describe the open field test

A
  • 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
16
Q

Describe the elevated plus maze

A
  • 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
17
Q

Describe novelty-induced hypophagia

A

Reduction in feeding in response to anxiety

18
Q

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

A
  • 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
19
Q

Describe olfactory bulbectomy as an animal model of depression

A
  • 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
20
Q

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

A
  • 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
21
Q

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

A
  • Stress - decreases in synaptic strength and spine loss
  • AMPAR - increases in synaptic strength and synaptogenesis
22
Q

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

A
  • 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
23
Q

Describe the antidepressant action of tianeptine

A
  • 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
24
Q

Describe the role of prefrontal cortex activity in depression

A
  • Connections between the medial prefrontal cortex mediate associations between environmental stimuli and reward
  • Prefrontal activity and spine density is reduced in depression
25
Q

Describe the role of the hippocampus in depression

A
  • 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