11 - Behavioural Neuropharmacology Flashcards
Why do we need animal models
Preclinical testing
What are the 3 Rs of animal testing
Replacement
Reduction
Refinement
What are the 3 validity criteria of animal models
1) Face validity - response in animal model should resemble behavioural response observed in humans
2) Predictive validity - animal model should be sensitive to clinically effective pharmacological agents
3) Construct validity - Theoretical and empirical accounts of the human disorder and the disordered behaviour is aligned
What does an animal model with better construct validity better parallel
Behavioural
Neurobiological
Genetic
Molecular features of the human disorder
What are 4 anxiety disorders
Generalised Anxiety Disorder
Panic Disorder
Acute Stress Disorder
Phobias
What do exploratory models of anxiety mimic
Natural conflict between tendency of a mice or rat to explore a novel environment and to avoid an exposed, open area
What are four exploratory models of anxiety
1) Open Field
2) Emergence or Light Dark Test
3) Elevated Plus Maze
4) Social Interaction
What is the innate fear model
1) Rats exposed to cat odour during conditioning
2) Predator odour induce an innate anxiogenic response
3) Midazolam during conditioning reversed anxiety
Is PTSD classified as anxiety or mood disorder
No
What are symptoms of unipolar depressive disorder (5)
1) Depressed mood
2) Apathy
3) Anhedonia
4) Difficulty to think or concentrate
5) Suicidal thoughts
What are some animal models of depression (4)
1) Behavioural despair (forced swim, tail suspension)
2) Learned helplessness (chronic unpredictable stress)
3) Chronic mild stress
4) Novelty-induced hypophagia
What is the effect of an antidepressant in the FST
Decreased immobility
What gene is associated with major depressive disorder
P2RX7
What is a prepulse inhibition of startle
Pre-exposure to a weak acoustic simulus reduces the startle response to a loud stimulus
What do schizophrenic patients show deficits in
PPI that are normalised by antipychotic drugs and nicotine
What does THC exposure reduce
Neurobehavioural effects of risperidone
What is a mutated protein implicated in schziphrenia
Neuregelin
Nrg1 heterozygous mice display hyperactivity and decreased PPI
What reversed Nrg1 hyperactivity
Clozapine
What did Nrg1 HET mice display
Enhanced sensitivity to drugs that trigger psychosis in humans e.g. methamphetamine and THC
What do Nrg1 HET mice have (3)
Increased c-Fos expression in the nucleus accumbens
Altered D2, 5-HT2A and NMDA receptor
Increased C4 expression
What do schizophrenia patients have increased defects in
Hippocampal 2-AG and cognitive deficits
What do 70-80% of children have a mutation in for Dravet syndrom
Loss-of-function in SCN1A
What does Dravet syndrome present as
Convulsive febrile seizures
Progress to spontaneous seizures and reduced lifespan
What behavioural abnormalities do affected children have
Hyperactivity
Psychomotor and language delays
Cognitive impairments
Difficulty socially relating to others
