Anxiety and Depression II animal models

Question 1

what is a model

Answer 1

small measure
a simplified representation used to explain the workings of a real system

Question 2

why do we use models

Answer 2

understand functions of the specific pathways/processes
study genetic/environmental factors
understand intervention/treatment
prevention

Question 3

animals used for models

Answer 3

worms
zebrafish
fruit flies
non-human primates (unethical and expensive)
rodents (phylogeny shows close relation to humans)

Question 4

similarities and differences between rodent/human brains

Answer 4

size
cortex is smooth
smaller cortex in rodents
larger have larger OB (more genes encode ORs)

Question 5

immemorial association between humans and rodents

Answer 5

commensal relationship
mice benefit from humans/humans are unaffected (sharing of food)
neolithic transition - nomadic hunters (farmers)
same environmental influences on man/mouse

Question 6

behaviour vs activity

Answer 6

behaviour = observed animal activity
activity = voluntary/involuntary movements made by conscious/unrestrained animals

Question 7

what does current behavioural research use

Answer 7

skinnerian (operant conditioning ) and ethological approach (animals in their natural environment)
skinner - little opportunity to use natural behaviour (trained)
ethological/spontaneous - use innate behaviour of animals (exploration of novel environment)

Question 8

fear vs anxiety

Answer 8

fear = response to an actual threat, move away from stimulus (triggers fight or flight)
anxiety = response to a potential threat, move towards the stimulus

Question 9

anxiety tasks with no conditioning

Answer 9

open field area (more locomotion=less anxiety, locomotor activity is confound for all behavioural tests)
light-dark box (anxiety = avoids light)
elevated plus maze

Question 10

activity tasks

Answer 10

running wheel
home cage
telemetry

Question 11

fear tasks with conditioning

Answer 11

give electric shock (threat)
response/freeze to a stimulus
cognitive task (emotional memory)
map anatomical pathways involved in fear conditioning

Question 12

social behaviour tasks with no conditioning

Answer 12

social dominance
social interaction test
exhibit behaviours: boxing/kicking/nosing/wrestlin/biting/anhedonia

Question 13

depression tasks with conditioning

Answer 13

learned helplessness (Seligman & Maier, 1967) inescapable shock, fail to escape when able, acute antidepressants increase escape
limitation: unethical, severe stress, strain differences, short lasting, not all animals develop helpless behaviour

Question 14

depression tasks with no conditioning

Answer 14

tests helplessness - how long until give up
Porsolt swim test/tail suspension test
limitation: unethical

Question 15

assessing validity of behavioural tasks

Answer 15

construct validity - how well the model reflects the theoretical assumptions
predictive validity - how well manipulation predicts performance in the condition being modelled
face validity - degree of similarity between the responses observed in the model and the disorder it stimulates

Question 16

confounding factors

Answer 16

health and physical ability
sensory abilities
locomotor activity and anxiety
motivation and drive
sex/age
test environment

Question 17

factors to consider for drug screening tests

Answer 17

efficiency - minimal time and effort expended in providing data
economy - minimal financial cost of animals, recording equipment and personnel training
reproducibility - consistency of results obtained
analytical facility - sustainability of the data by use of statistical methods

Question 18

Genetic models

based on biology not GWAS

Answer 18

monoamine hypothesis - depletion of tryptophan (reduces 5-HT), typical antidepressants increase monoamines
dysregulation of the HPA axis - increased cortisol in depression, poor negative feedback, antidepressants improve feedback
neurogenesis hypothesis - stress causes hippocampal neuronal death, antidepressants increase neurogenesis
other - circadian clock, inflammation

Question 19

Cryan & Sweeney 2011

Answer 19

monogenic approach
5HTT KO causes increased anxiety in light-dark box/elevated maze
identify genes (BALB/C)

Question 20

future models

Answer 20

combine genetic and environmental manipulations
double hit
distal (early life) proximal (adult life)
consider individual susceptibility
form for sophisticated and sensitive tests

Question 21

challenges of models

Answer 21

MURIDAE
modalities for understanding, recording, and integrating data across early life

Question 22

chronic unpredictable mild stress model

Wilner et al., 1992

Answer 22

repeated exposure to mild stressors, type and durations of stressors
poor reproducibility
strain selection
physical and psychosocial stressors

Question 23

maternal separation model

Answer 23

separate pups from mother
day 2-14 pups - 3hr separation
day 9 pups - 24hr separation
poor reproducibility
selected strain (susceptible)
physical and psychosocial stressors

Question 24

social defeat

Answer 24

continuous contact with aggressor for 10-20 days
long lasting social aversion
increase anxiety/immobility - downregulation of BDNF transcripts
reversed by chronic antidepressant
poor reproducibility
unethical
strain selection

Question 25

olfactory bulbectomy

Answer 25

removal of the olfactory bulb (used in limbic-hypothalamic axis)
sensory deprivation
hyperactivity in novel environment (increase noctural hyperactivity)
passive avoidance defeat
deficits in spatial memory
poorly understood
altered monoamine NTs - reversed by chronic antidepressants