Depression Animal Models

Question 1

Why is it probably not true that low 5HT causes low mood?

Answer 1

Drugs take days/weeks to solve symptoms

They increase 5HT fairly quickly

Question 2

What other pathological mechanism has been proposed for depression?

Answer 2

Reduced neurogenesis in the hippocampus

Question 3

How many SSRIs treat depression then?

Answer 3

Increase neurogenesis in the hippocampus
Stimulate brain derived neurotrophic factor production
This promotes neuronal growth

Question 4

How can animal models be created?

Answer 4

Drug treatment 
Genetic alteration
Selective breeding
Experience
Surgery

Question 5

What is face validity?

Answer 5

Do the model symptoms look like the clinical disease?

At face value

Question 6

What is construct validity?

Answer 6

Does the pathophysiology mirror humans?

Question 7

What is the predictive validity?

Answer 7

Ability to predict the efficacy of treatment

Question 8

Which type of validity is highest in animal models?

Answer 8

Construct validity

Question 9

Which type of validity is highest in behavioural tests and drug models?

Answer 9

Predictive

Question 10

What main surgery is used to create a depression model

Answer 10

Olfactory bulbectomy

Question 11

Which type of validity is highest in olfactory bulbectomy model?

Answer 11

Predictive - the medications which treat this in rodents are good in humans but we don’t know why

Low construct

Question 12

Which receptor is reduced in depression leading to increased HPA activity?

Answer 12

Glucocorticoid receptor

More glucocorticoid, but less negative feedback in the HPA, so overall more glucocorticoid

Question 13

How is the glucocorticoid receptor theory supported in animal models?

Answer 13

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

Question 14

Which do we think nicotinic antagonists may be useful in depression?

Answer 14

Dose dependently been shown to increase the amount of time spent swimming in the forced swim test

Andreasen 2009

Question 15

Which tests can be done to measure recognition and despair?

Answer 15

Forced swim

Tail suspension

Question 16

Describe the forced swim test

Answer 16

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

Question 17

Describe the tail suspension test

Answer 17

Hung by tail and measure time until stop trying to escape

Same premise, pros and cons as forced swim

Question 18

What can be used to assess learned helplessness in rodents?

Answer 18

Shuttle box task

Question 19

Describe the shuttle box task

Answer 19

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

Question 20

What is the effect of BDNF on learned helplessness?

Answer 20

Dose dependently reduced failures and escape latency in the shuttle box task

Shirayama et al 2002

Question 21

What can be used to test for anhedonia?

Answer 21

Sucrose preference test

Intra-cranial self-stimulation

Question 22

Describe sucrose preference test

Answer 22

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

Question 23

Describe the intra-cranial self stimulation test

Answer 23

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

Question 24

What is the model valid behavioural model for depression? Why?

Answer 24

Chronic Mild Stress

Selective for depression. Causes long lasting behaviour change.

Question 25

How may a chronic mild stress model be created?

Answer 25

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

Question 26

Which tests can be used to measure anxiety?

Answer 26

Light/dark box
Open field
Elevated plus maze
Novelty induced hypophagia

Question 27

How does the early life stress model work?

Answer 27

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

Question 28

Which sex is more affected by ELS?

Answer 28

Female

Question 29

Explain the social defeat model

Answer 29

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

Question 30

What are the pros and cons of the social defeat model?

Answer 30

Pros: good predictive, face and construct validity
Cons: time consuming, expensive, can only use male mice