Depression Animal Models Flashcards
Why is it probably not true that low 5HT causes low mood?
Drugs take days/weeks to solve symptoms
They increase 5HT fairly quickly
What other pathological mechanism has been proposed for depression?
Reduced neurogenesis in the hippocampus
How many SSRIs treat depression then?
Increase neurogenesis in the hippocampus
Stimulate brain derived neurotrophic factor production
This promotes neuronal growth
How can animal models be created?
Drug treatment Genetic alteration Selective breeding Experience Surgery
What is face validity?
Do the model symptoms look like the clinical disease?
At face value
What is construct validity?
Does the pathophysiology mirror humans?
What is the predictive validity?
Ability to predict the efficacy of treatment
Which type of validity is highest in animal models?
Construct validity
Which type of validity is highest in behavioural tests and drug models?
Predictive
What main surgery is used to create a depression model
Olfactory bulbectomy
Which type of validity is highest in olfactory bulbectomy model?
Predictive - the medications which treat this in rodents are good in humans but we don’t know why
Low construct
Which receptor is reduced in depression leading to increased HPA activity?
Glucocorticoid receptor
More glucocorticoid, but less negative feedback in the HPA, so overall more glucocorticoid
How is the glucocorticoid receptor theory supported in animal models?
GR +/- mice have:
Increased learned helplessness in stress shown by increased latency in the shuttle box task
Less hippocampal BDNF and decreases neurogenesis
Riddler et al 2005
Which do we think nicotinic antagonists may be useful in depression?
Dose dependently been shown to increase the amount of time spent swimming in the forced swim test
Andreasen 2009
Which tests can be done to measure recognition and despair?
Forced swim
Tail suspension
Describe the forced swim test
Mice in cylinder full of water
Time them to see what time is spent immobile (in despair)
Pros: cheap, easy, fast, good predic value for MA drug
Cons: poor face and construct validity bc only shows acute effects
Describe the tail suspension test
Hung by tail and measure time until stop trying to escape
Same premise, pros and cons as forced swim
What can be used to assess learned helplessness in rodents?
Shuttle box task
Describe the shuttle box task
Shock given in a box with two compartments
One you get a shock one you don’t
If the shock is unpredictable the animal feels more helpless and passively remains in the shock compartment
Pros: good face validity
Cons: needs strong stressor and symptoms may not last long after
What is the effect of BDNF on learned helplessness?
Dose dependently reduced failures and escape latency in the shuttle box task
Shirayama et al 2002
What can be used to test for anhedonia?
Sucrose preference test
Intra-cranial self-stimulation
Describe sucrose preference test
Given two bottles and a choice between one with sucrose and one just water
If the mice shows no preference for sucrose > water, it can be assumed they are not perceiving it a pleasurable
Describe the intra-cranial self stimulation test
Hypothalamic electrodes are placed in brain
Can be self stimulated by pressing lever
If doesn’t really take interest in the lever, can assume the animal is not perceiving it as pleasurable
What is the model valid behavioural model for depression? Why?
Chronic Mild Stress
Selective for depression. Causes long lasting behaviour change.
How may a chronic mild stress model be created?
Get various stressors, different everyday for up to three weeks
ie keep lights on; 4hours of white noise; removal of bedding; food and water depravation; cage tilt for 8 hours
Which tests can be used to measure anxiety?
Light/dark box
Open field
Elevated plus maze
Novelty induced hypophagia
How does the early life stress model work?
Several ways to induce this
Common to do maternal separation via reduced bedding
Leads to anhedonia later in life as shown by anhendonia tests. Less ICSS in michaels et al 2007
Which sex is more affected by ELS?
Female
Explain the social defeat model
Expose a rodent repeatedly to a dominant animal to promote aversion in subsequent social interaction
Anxiety within 10 days, depression within 20, 14 days in Yu et al 2011
What are the pros and cons of the social defeat model?
Pros: good predictive, face and construct validity
Cons: time consuming, expensive, can only use male mice
