Animal Modes and Drugs effects on neurons

Question 1

What is an animal model?

Answer 1

Involves using a laboratory animal in a specific testing situation to determine the behavioural changes induced by a drug,

leading to a genetic manipulation or some manipulation of the brain

Question 2

Examples of a genetic manipulation

Answer 2

Gene knockout or gene over-expression

Question 3

Examples of manipulations of the brain

Answer 3

Electrical stimulation, lesion or injection of the drug directly to the brain

Question 4

Predictive validity

Answer 4

The utility of a behaviour test

Question 5

General rule of ethics with animals

Answer 5

The less harmful the test the better it is

Question 6

How can we infer the

psychological state of an animal

Answer 6

It overt behaviour

Question 7

How much do drug companies spend a year on R&D and what is the biggest area of research?

Answer 7

$30billion a year
CNS medication (drugs for depression anxiety etc)

Question 8

Understanding functional genomics (in terms of mice)

Answer 8

There are currently more than 10,000 knockout mice and many thousands of more types with random mutations. An important effort relates to phenotyping these mice: exploring how the mutation or deletion of genes affects behaviour

Question 9

Broad areas animal models are widely used in?

Answer 9

Behavioural neuroscience - what part of the brain does what

psychopharmacology - assessing acute and long-term effects of drugs

Question 10

What did THC (canabis) change about the behaviour of the rat?

Answer 10

Very still, indifferent, bit more anxious

Question 11

Describe the hotplate test and what it allows

Answer 11

Rats are placed on
a hot plate (approximately 50ºC) and the time taken for them to start licking their hind paws is assessed.

The hot plate
test is important when investigating new analgesic (pain relieving) drugs.

A greater latency to lick paws is indicative of an analgesic effect of a drug.

Question 12

Does the hot plate cause tissue damage to the rat?

Answer 12

No but in experimental conditions has potential to

Question 13

Describe the bar test and what it tests

Answer 13

A rat is positioned so that its forepaws are resting over
the bar. The time taken for the rat to remove its forepaws from the bar is measured.

Assesses catalepsy

A drug that increases response latency in this test has “cataleptogenic” properties and may well impair motor
function in humans.

Question 14

What is catalepsy?

Answer 14

A characteristic waxy immobility that is seen

in rats after high doses of specific drugs.

Question 15

What drugs cause catalepsy in rats?

Answer 15

Opiods, Bemps, Cannaborids

Question 16

Describe the elevated plus maze and what it tests

Answer 16

Two arms of the EPM have
enclosed walls, while the other two are open. It exploits the rats natural fear of open spaces, and its preference for maintaining vibrissal (whiskers) contact with its environment. Normally, a rat
will spend about 80% of its time in the enclosed arms.

Tests for anxiety

Question 17

gat does anxiolytic drug lead to in plus maze?

Answer 17

Less anxiety, more ok with it

Question 18

Problems with testing alcohol on plus maze

Answer 18

Might fall off or be immobile

Question 19

What is the brand name of chlordiazepoxide?

Answer 19

Librium

Question 20

What is stereotypy?

Answer 20

Repetitive, stereotyped and seemingly purposeless behaviour (e.g. head
weaving) that is induced by high doses or repeated doses of stimulant drugs.

It can be observed in
both rodents and humans. It is associated with a hyperdopaminergic state in the dorsal and ventral
striatum

Question 21

What often causes stereotypy?

Answer 21

Behavioural and neurochemical sensitisation

Question 22

Describe the effects of high dose amphetamine on behaviour

Answer 22

Heightened stereotypy behaviour

Question 23

What kind of drug can be given to block stereotypy induced by amphetamine?

Answer 23

Dopamine antagonist, Fluphefarmine

Question 24

What was the difference between pure THC and THC+cannabidiol?

Answer 24

THC: Highly anxious, suspicious

THC + Cannbidiol: happy, relaxed

Question 25

Effects of smoking high THC level marijuana

Answer 25

More depressive, anxious state

however really depends on the person - higher for those with predisposition for scrutiny

Question 26

Benefits of conducting research into psychoactive drugs on human volunteers?

Answer 26

Real time info
Descriptive understanding
More valid

Question 27

Limitations of conducting research into psychoactive drugs on human volunteers?

Answer 27

Ethical issues
Quite subjective
Not as much control over prior factors

Question 28

4 major ways drugs can alter neurotransmission:

Answer 28

1. Increasing neurotransmitter release from vesicles
2. Inhibition or reversal of transporter proteins
3. Inhibiting neurotransmitter degradation
4. Directly binding to receptors

Question 29

Increasing neurotransmitter release from vesicles

Answer 29

Neurotransmitters are stored in synaptic vesicles and are released into the synaptic cleft as a consequence of action potentials. A drug may interact with vesicles to increase neurotransmitter
release.

Amphetamine and cocaine

Question 30

Inhibition or reversal of transporter proteins

Answer 30

Drugs may bind to transporter proteins, either to inhibit the reuptake of neurotransmitter to the terminal, or by making the transporter work in reverse. In the latter process,
the transporter now ferries the neurotransmitter from the terminal to the synapse. In both instances, this will prolong the action of the neurotransmitter at its receptors.

Cocaine, amphetamine and MDMA, common antidepressants

Question 31

Define reuptake

Answer 31

Transporter proteins ferry the neurotransmitter back from the synapse into the terminal, for repackaging into vesicles

Question 32

2 purposes of reuptake

Answer 32

(1) To terminate the action of the neurotransmitter at its respective receptor and
(2) to recycle neurotransmitter (the need to synthesise more neurotransmitter is lessened).

Question 33

What is monomine oxidase (MAO) and what two forms is it present in?

Answer 33

Important enzyme with respect to drugs of abuse

MAO-A, which preferentially metabolises serotonin, and

MAO-B, which preferentially
metabolises dopamine

Question 34

Inhibiting neurotransmitter degradation

Answer 34

By inhibiting MAO, the affected neurotransmitter will remain in the synapse
for longer, thereby prolonging its action at its receptors.

Question 35

Directly binding to receptors

Answer 35

Drug may directly bind to a receptor, mimicking the neurotransmitter

This can either evoke a functional change to the neuron (agonist) or prevent this change from occurring (antagonist).

Drugs that bind to a receptor will usually have a structure very similar to the neurotransmitter that binds the same receptor

E.g. THC, nicotine, Herion

Question 36

Ecstasy:

1. Name two neurotransmitter systems that it acts on.
2. Positive and negative effects
3. In which two ways does MDMA interact with serotonin
4. How might MDMA precipitate depression in heavy or chronic users?

Answer 36

1. Serotonin, moradrenaline
2. Better stamina and feelings of compassion and empathy, but can cause dehydration, memory loss and brain damage (destroying nerve cell axons and decrease blood flow)
3. a) Blocks the return of serotonin to the axon, bind to the reuptake protein itself, preventing serotonin from entering.
   b) Alters the shape of the reuptake protein, sending serotonin from the axon terminal to the synapse
4. Ecstasy use can deplete the supply of serotonin in your brain and desensitize receptors. This is most noticable a few days after use. You can feel a bit depressed, irritable and emotionally sensitive.

Question 37

Speed

1. Which neurotransmitter systems does amphetamine affect?
2. Name 3 mechanisms through which it affects these neurotransmitters.
3. What physiological effects does amphetamine produce?

Answer 37

1. Dopamine and noradrenaliine (both involved in transporting information between neurons
2. a) arrives in the brain via the blood. It Penetrates into neurons with the aid of reuptake proteins. In the axon terminal, speed causes the neurotransmitter vesicles to release all of their noradrenaline or dopamine. These transmitters then move across the synapse to the receptors on the next cell, relaying the signal further.
   b) Blocks reuptake of transmitters back to axon
   c) Blocks MAOs breakdown
3. Can arouse pleasure and euphoria and make you feel energetic

Question 38

Cocaine

1. What are the effects?
2. Describe 2 ways in which cocaine increases dopamine release

Answer 38

1. Intensifies release of dopamine
2. a) Cocaine molecules bind to the reuptake proteins. Blocks access
   b) The dopamine drifts about in the cleft and collides with the receptors. The release of dopamine also continues, so that increasing amounts of it accumulate in the synaptic cleft.

Question 39

Cannabis:

1. Effects
2. What neurotransmitter does THC mimic?
3. How does THC indirectly stimulate the release of dopamine n the nucleus accumbens?
4. % of dependent users, why it is less addictive
5. Four regions of the brain have a high density of
   cannabinoid receptors, and what role do these regions have in mediating the effects of cannabis

Answer 39

1/ relaxed, contented and slightly intoxacted, coordination problems, impairment of memory

2. Anandamide (binds to receptors)
3. Indirect, through GABA (inhibits excessive release of dopamine), interferes with GABA so more dopamine is released
4. 10%, less dopamine is released in comparison

5:
hippocampus - interferes with short term memory
hypothalamus - induce hunger
cerbellum - coordination and balance
basal ganglia - physical coordination, involuntary

Question 40

Herion:
1. 3 effects

2. name an endogenous opiate
3. Explain how opiates indirectly stimulate dopamine release
4. Why can heroin overdose lead to suffocation?

Answer 40

1. pleasure, pain relief and suppression of breathing
2. Morphine
3. Inhibits GABA release, slower to breakdown and dopamine persists
   b) also binds to dopamine but can’t keep it under control
4. Strongly effects breathing rhythm. The neurons that regulate breathing contain opioid receptors. When binding to receptors, it leads to a suppression of signal transmission to the breathing muscles. Breathing becomes shallower.

In the event of an overdose of heroin, the suppression of breathing is so powerful that the lungs come to a standstill, as it were. Breathing is no longer possible, and you suffocate.

Question 41

Alcohol:

1. 5 neurotransmitter systems
2. Effects of increased GABA release
3. How does it interact with GABA receptors
4. Effect on cerebellum (high density GABA)
5. the neural mechanism that underpins alcohol tolerance?
6. Symptoms of alcohol withdrawal

Answer 41

1. dopamine, serotonin, endorphin, GABA and glutamate.
2. GABA has an inhibitory effect on other neurons, and thus causes certain parts of the brain to work more slowly.
3. Alcohol binds to the GABA receptor, too, but at a different site from where GABA binds. When GABA and alcohol are bound to the receptor at the same time, GABA stays bound to it longer than usual. Sends its inhibitory message to the receiving neuron for a longer period of time and GABA binds more frequently
4. Alcohol reduces your fine motor control, because your cerebellum slows down.
5. Alcohol blocks glutamate receptors. When the neurons containing these receptors sense that some receptors have been blocked, they increase the sensitivity of the receptors and generate additional ones. To continue blocking the excitatory action of glutamate, you need to drink more and more alcohol.
6. Insomnia, jitteriness, sweating, anxiety and depression