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ANIMAL MODELS IN

PSYCHOPHARMACOLOGY
ANİMAL MODEL
A living organism with an inherited, naturally acquired or induced
pathological process that in one or more aspects closely
resembles the same phenomenen in humans.
WHY DO WE CONDUCT
ANİMAL STUDİES?
Development of treatment protocols
Development of surgical procedures
Investigation of the ethiology
Exploration of the genetic processes underlying and
contributing the pathology.
Physiology/behavioural physiology
Understanding the effects of drugs, chemicals and other
substances exposed.
Deeper investigation into the emotional, cognitive and
behavioural processes and their interactions.
Social behaviour
ANİMALS USED İN
RESEARCH
Rodents
Non-rodents (Rabbit, monkey, insects, fish)
Genetically modified animals
Transgenic animals: A foreign gene inserted into the genome
Knock-out animals: One or more genes are inactivated

*In behaviour studies, female menstrual cycle is considered to be a


confounding factor therefore traditionally only male animals are
included.
ANİMALS
ANIMAL STUDIES OF
BEHAVIOUR
Classical conditioning Operant conditioning
(Pavlov) (Skinner-1938)

Learned Helplessness
(Seligman-1967)
CRİTERİA FOR THE ANİMAL
MODELS

ü Face Validity: Symptomatological similarity


«How similar is the model with the disorder?»

ü Construct Validity: Ethiological similarity


«Are the theoretical accounts for explaining the disorder valid for the
model?»

ü Predictive Validity: Treatment and prognosis similarity


«Are the prognosis or the treatment of the human condition valid for the
model?»
PSYHOPATHOLOGİES
Anxiety disorders
OCD, PTSD, panic disorder, phobias
Mood disorders
Depression, bipolar disorder (?)
Psychotic disorders?
Substance addiction
Sexual dysfunctions
STRESSORS İN ANİMAL MODELS

Stressors Stressor dose

üPhysical stressors (water ü Social instability üSingle stressor

immersion/forced swim, ü Social defeat üSingle prolonged

Electric shock, ü Social isolation stress

Immobilizatin) üChronic stress

üPsychological stressors (predictable/unpredi

(Predator)
, ctable)

9
PHYSICAL STRESSORS
ELECTRIC SHOCK IMMOBILISATION
PSYCHOLOGICAL STRESSORS
PREDATOR OR CUE FEROMONES
SOCİAL STRESSORS
SOCIAL ISOLATION SOCIAL INSTABILITY
Animal being Animals caged in
isolated pairs and their cage
Has dramatic mate is changed
especially when every day
started from infancy
SOCİAL DEFEAT

https://www.youtube.
com/watch?v=WW6-
4KZIPe8
STRESSOR DOSE AND
DURATİON
üSingle stress

üSingle prolonged stress

üChronic stress

üMild stress/ intense stress


ANIMAL MODELS OF ANXIETY
Fear is the response against an actual and immediate threat.
Anxiety is an agitation and worry response towards a
potential or perceived threat.

Characterized by prolonged fight-flight response and


misinterpretation of the symphatetic activation.

Fear conditioning is the central paradigm in animal models of


anxiety
FEAR AND ANXİETY İN ANİMAL MODELS

Conditioned Fear Sensitized fear Other


Measurements ü Neophobia(OF/ üLearning and
Contextual fear
MHT) memory (Radial arm
conditioning ü Anxiety (EPM) water maze /New
+ Cued fear conditioning ü Startle Paradigm object recognition)
üAcquisition (AST) üLocomotor activity
üExtinction (OF)
üExtinction retention üSleep (EEG)

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CLASSİCAL CONDİTİONİNG
PARADİGM
Acquisition: The
Cued fear conditioning: emergence of fear
Conditioning takes place reactions towards a
to a neutral cue neutral stimulus paired
with a feared one.
Contextual fear
conditioning: Extinction: Fear reaction
Conditioning takes place is expected to diminish
to the context with repeated
presentation of neutral
stimulus.

Avoidance : active and


passive avoidance

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ELEVATED PLUS MAZE
Anxiety Like Behaviour
(ALB): Time the animal
has spent on the open arm
Extreme Behavioural
Manifestation of Anxiety-
EBMA): No entrance into
the open arms
Resillience: 1 minute time
spent in the open arm
and/or 8 or more entries

18
HOLEBOARD TESTİ
https://www.youtu
be.com/watch?v=
GROOCu6bLTM
Exploration of the
holes decrease in
response to
ACOUSTİC STARTLE REFLEX
The magnitude of
the startle
response before
or after a stress
procedure

https://www.youtu
be.com/watch?v=
Kfu0FAAu-10
SENSİTİZED (NON-
ASSOCİATİVE) FEAR
Measurement of fear response to a new or neutral
environment or stimulus.
Acoustic startle paradigm: The magnitude of the startle
response to an unexpected loud noise.
Neophobia measurements are also interpreted as signs of
non-associative fear response.

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LİGHT/DARK TEST
Natural
orientation of the
rodents are
towards darkness
The rats exposed
to stressor in the
dark chamber
stay in the light
chamber.
DEPRESSİON
Depressed mood
Anhedonia
Lack of or excessive appettite
Insomnia orhipersomnia
Psychomotor agitation or lethargy
Feelings of worthlessness and/or guilt
Difficulties in concentration and focusing
Suicidal thoughts
DEPRESSİON MODELLİNG İN
ANİMALS
Stressor administration
Social isolation
Lesions in the limbic system
Serotonin antagonism
ASSESSMENT OF THE
DEPRESSİON MODELS
Forced swim test
Locomotor activity tests
Learning and memory skills
Measurements of food consumption and body weight

Most assessments are based on predictive validity:


«Does the antidepressants reverse the symptoms in the
model?»
FORCED SWİM TEST

Forced swim test: Based on the «learned helplessness model of


depression»

https://www.youtube.com/watch?v=B_7qqOhr8QM
OPEN FİELD TEST

Measurement of locomotor activity:

Ambulation: Crossing the squares

Entrance into the middle squares

Immobility: Freezing

The measurements can also be


interpreted as «neophobia»
https://www.youtube.com/watch?v=g
JDV2cp8w9E&t=1s&ab_channel=Maz
eEngineers

27
WATER MAZE

Learning the hidden platform to exit from the water filled tank.
Chronic stress impairs learning and memory.

https://www.youtube.com/watch?v=leHLL4vcbCc&ab_channel=cu
ongtrinh

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SUBSTANCE ADDİCTİON MODELS
Excessive occupation with the substance
Difficulty cutting down or ceasing the use of substance despite
motivation
Withdrawal
Impairment in daily life and functioning
Continuing the use of the substance despite danger,
dysfunctioning or loss of health.
Tolerance: Needing more substance
ANİMAL MODELS OF ADDİCTİON
Drug seeking behaviour can be modelled in animals through
positive reinforcement paradigm
https://www.youtube.com/watch?v=AldELIGAZik&ab_channe
l=HeriVaz

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