Psychopharmacology 1

Question 1

What is psychopharmacology

Answer 1

The process of understanding the neurochemical action of drugs that yield a specific behavioural effect

Question 2

What is important to remember regarding the dose of the drug and what reaches the target site

Answer 2

Much less due to - lipid storage and excretion

Question 3

`Why are drugs given repetitively over time

Answer 3

To increase the dose to the desired drug level as with each dose a percentage of this is washed out

Question 4

What factors affect drug absorption and distribution

Answer 4

Age
Gender
Weight
Diffusion
Lipid solubility
Ionisation
BBB
Drug transport across membranes

Question 5

What determines the dose-response relationship

Answer 5

Greater response with a higher affinity for its receptor, which in turn elicits a response

Question 6

What are the three different behavioural animal models

Answer 6

Behavioural bioassays - brain-centred

Simulations - mind-centred

Screening test - drug-centred

Question 7

What are behavioural bioassays

Answer 7

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

Question 8

What are the benefits of behavioural bioassays

Answer 8

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

Question 9

What are simulations

Answer 9

Use of animals to understand human mental processess by simulating a symptom or syndrome associated with a disorder

Question 10

How are simulations developed

Answer 10

Brain damage
Selective breeding
Application of cause of disease - ageing, social isolation

Question 11

What are screening tests

Answer 11

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

Question 12

What is face validity

Answer 12

Model resembles disorder and no major dissimialrities

Question 13

What is construct validity

Answer 13

Has a sound theoretical rationale with the same cause and pathogenesis

Question 14

What is predictive validity

Answer 14

Performance in test predicts performance in condition being modeled and can we use the same pharmacological treatments

Question 15

Give some models for obesity

Answer 15

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)

Question 16

Give some examples of anorexia models

Answer 16

Hypothalamus lesion - apathy and possible recovery
Nigrostriatal DA lesions - aphagia and sensory neglect
Pharmacological treatment with amphetamines (stimulate dopamine)

Question 17

How is anxiety modelled in animals

Answer 17

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.

Question 18

How is depression modelled in animals

Answer 18

Behavioural tests to screen antidepressant drugs -

Via vulnerability - early life events like maternal separation
Triggering factors - stress like chronic dirty bedding
Drug-induced

Question 19

What is apathy and why is it important

Answer 19

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.

Question 20

What is the current treatment for apathy

Answer 20

Disease dependent but cholinesterase inhibitors in Alzheimer’s disease but inconclusive
Dopamine agonists might have some benefits

Question 21

What models can be used for apathy

Answer 21

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).

Question 22

What models are used for cognition

Answer 22

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

Question 23

Give some behavioural tests for cognition tests

Answer 23

Morris-water maze
Stone maze
Barnes maze
Y maze/T maze
Operant task - level pressing in response to stimuli

Question 24

Give some behavioural tests seen for animal models for depression

Answer 24

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

Question 25

Give an example of how behavioural bioassays have been used for

WIDER READING - (Jacobson et al., 1976)

Answer 25

Hormones - sex pheromones by measuring moth wing flapping behaviour

Question 26

How had phencyclidine (pharmacological inducer of schizophrenia behaviours) convey apathy in mice

WIDER READING - (Pedersen et al., 2014)

Answer 26

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

Question 27

How had chronic social defeat stress shown causes of apathy in mice (CSDS)

WIDER READING - Denmark et al 2010

Answer 27

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.

Question 28

How did CSDS help identify the neurophysiology underlying its relation to apathy

WIDER READING - Azzinnari et al 2014

Answer 28

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

Question 29

How have transgenic mice been modelled for apathy in PD

WIDER READING - Baumann et al 2016

Answer 29

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

Question 30

What was shown in mice ADLs when hippocampal lesions were present

WIDER READING - Deacon et al 2012

Answer 30

Nest building from 4/5 to a median of 1-2

Burrowing median from 70g to <5g

Question 31

Why is the open field test a poor test for anxiety

WIDER READING - Bourin et al 2007

Answer 31

Too variable - different shape of field, size, colour, lighting.

Question 32

How were mice models of anxiety used to try herbal medicine against SSRI

WIDER READING - Doron et al 2012

Answer 32

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

Question 33

How was the 129 mouse a good model for schizophrenia using the barnes maze.

WIDER READING - Riedel 2018

Answer 33

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