Psychopharmacology 1 Flashcards
What is psychopharmacology
The process of understanding the neurochemical action of drugs that yield a specific behavioural effect
What is important to remember regarding the dose of the drug and what reaches the target site
Much less due to - lipid storage and excretion
`Why are drugs given repetitively over time
To increase the dose to the desired drug level as with each dose a percentage of this is washed out
What factors affect drug absorption and distribution
Age
Gender
Weight
Diffusion
Lipid solubility
Ionisation
BBB
Drug transport across membranes
What determines the dose-response relationship
Greater response with a higher affinity for its receptor, which in turn elicits a response
What are the three different behavioural animal models
Behavioural bioassays - brain-centred
Simulations - mind-centred
Screening test - drug-centred
What are behavioural bioassays
Look at physiological action on the whole animal
Commonly used to study mechanisms responsible for changed in brain function using -
- acute/chronic drug administration
- Brain lesions
What are the benefits of behavioural bioassays
Non-destructive
Agents reach the brain and are not evident in the whole animal
Functional measures - can see how all the areas of the brain are effected
Integrates activity of the whole brain
What are simulations
Use of animals to understand human mental processess by simulating a symptom or syndrome associated with a disorder
How are simulations developed
Brain damage
Selective breeding
Application of cause of disease - ageing, social isolation
What are screening tests
Method used to develop new drugs by -
Identify agents/drugs that have specific clinical actions - anti-depressants, neuroleptic etc
Identify biochemical action as a target for drug development
What is face validity
Model resembles disorder and no major dissimialrities
What is construct validity
Has a sound theoretical rationale with the same cause and pathogenesis
What is predictive validity
Performance in test predicts performance in condition being modeled and can we use the same pharmacological treatments
Give some models for obesity
Hypotalamus lesions - best, increase in weight immediately
Dietary obesity - supermarket and cafeteria diet for animals
Social isolation - more overeating and depression
Genetic - zucker rats
Antipsychotic drugs - neuroleptics (clozapine) DA antagonists
Anxiolytics - pain killers benzos
Antidepressants (tricyclic antidepressants stimulate appetite)
Give some examples of anorexia models
Hypothalamus lesion - apathy and possible recovery
Nigrostriatal DA lesions - aphagia and sensory neglect
Pharmacological treatment with amphetamines (stimulate dopamine)
How is anxiety modelled in animals
Drug-induced
Behavioural test - open-field, light/dark crossing (more time in dark when anxious), elevated plus maze (open and closed at height), social interaction
Test medication on these.
How is depression modelled in animals
Behavioural tests to screen antidepressant drugs -
Via vulnerability - early life events like maternal separation
Triggering factors - stress like chronic dirty bedding
Drug-induced
What is apathy and why is it important
The loss of motivation, initiative and interest and the flattening of emotions. It affects 2/3 of - behaviour/cognition, emotional and social interaction.
Important because most common neuropsychiatric symptoms in neurodegenerative diseases are also typically one of the first.
Severe impact on daily living too.
What is the current treatment for apathy
Disease dependent but cholinesterase inhibitors in Alzheimer’s disease but inconclusive
Dopamine agonists might have some benefits
What models can be used for apathy
Need more than one due to the multidimensional nature of apathy. Examples include -
Reward-based operant conditional task - goal-directed behaviour (decreased in apathy)
Reduced exploration
Nest building - motivation to perform daily tasks (1-5 rating)
Voluntary sucrose intake (motivation and interest in pleasurable activities)
Sociability (no. of social interactions and the amount of time socialising).
What models are used for cognition
The ability to learn and show retention for spatial location and visual stimuli.
Drug-induced - socopolamine (muscarininc antagonist)
Lesion models - hippocampus
Transgenic models - Alzheimer’s disease mice
Give some behavioural tests for cognition tests
Morris-water maze
Stone maze
Barnes maze
Y maze/T maze
Operant task - level pressing in response to stimuli
Give some behavioural tests seen for animal models for depression
Tail suspension test - induces learned helplessness (how long does it take for them to give up - measures helplessness and depression)
Forced swim test - induces learned helplessness (how long does it take for them to give up - measures helplessness and depression)
Social and sociability interaction
Noticed via - poor coat condition, not nest building
Give an example of how behavioural bioassays have been used for
WIDER READING - (Jacobson et al., 1976)
Hormones - sex pheromones by measuring moth wing flapping behaviour
How had phencyclidine (pharmacological inducer of schizophrenia behaviours) convey apathy in mice
WIDER READING - (Pedersen et al., 2014)
Impaired nest building as detailed by the nesting index score showed that phencyclidine can be used as a method to induce negative symptoms of schizophrenia in rodents.
Also reversed with nicotinic α7 receptor agonists, opening a possible thereuputic agent
How had chronic social defeat stress shown causes of apathy in mice (CSDS)
WIDER READING - Denmark et al 2010
leads to disorganized patterning of grooming behaviors in subordinate mice. CSDS is a widely applied manipulation in rodent research and it is based on the finding that specific uncontrollable stressful life events are major aetiological factors in various neuropsychiatric disorders.
How did CSDS help identify the neurophysiology underlying its relation to apathy
WIDER READING - Azzinnari et al 2014
It was shown that CSDS affects dopamine function in specific brain regions, e.g., down-regulated expression of genes for dopamine receptors and signaling proteins
How have transgenic mice been modelled for apathy in PD
WIDER READING - Baumann et al 2016
Mice were used that were deficient in the vesicular monoamine transporter 2 (VMAT2).
Apathy behaviour shown via - impaired burrowing and nest building skills, and a reduced preference for sweet solution in the saccharin preference test, but normal swim test as expected.
This is a good model as can show apathy which is independent of depression. good for PD models
What was shown in mice ADLs when hippocampal lesions were present
WIDER READING - Deacon et al 2012
Nest building from 4/5 to a median of 1-2
Burrowing median from 70g to <5g
Why is the open field test a poor test for anxiety
WIDER READING - Bourin et al 2007
Too variable - different shape of field, size, colour, lighting.
How were mice models of anxiety used to try herbal medicine against SSRI
WIDER READING - Doron et al 2012
Used mice that were exposed to chronic stress during childhood to induce anxiety.
Trialed these mice with behvaioural tests - open field and elevated maze paradigms and tested BDNF and coricosterone levels.
This showed that - (1) the novel herbal treatment reduced anxiety-like behaviors in both behavioral tests. Interestingly, this reduction was observed only following a 3-week treatment; (2) following the novel treatment, corticosterone levels in the plasma of treated mice were reduced and this reduction was similar to the one observed following escitalopram treatment; and (3) BDNF levels in the hippocampus of mice treated both with the novel herbal treatment and escitalopram were increased.
Showed that it is just as good as the meds
How was the 129 mouse a good model for schizophrenia using the barnes maze.
WIDER READING - Riedel 2018
Used barnes maze of 8,16 and 32 holes.
Normal control mice were able to perform acquisition and reversal learning in all 3 mazes but 129 mice had impairments - 8-hole maze; intact acquisition, but impaired reversal, was evident in the 16-hole maze and the impaired acquisition was evident in the most difficult 32-hole test.
Therefore showed impaired cognition and behavioural flexibility so a good schizophrenia model
