Animal Modes and Drugs effects on neurons Flashcards
What is an animal model?
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
Examples of a genetic manipulation
Gene knockout or gene over-expression
Examples of manipulations of the brain
Electrical stimulation, lesion or injection of the drug directly to the brain
Predictive validity
The utility of a behaviour test
General rule of ethics with animals
The less harmful the test the better it is
How can we infer the
psychological state of an animal
It overt behaviour
How much do drug companies spend a year on R&D and what is the biggest area of research?
$30billion a year CNS medication (drugs for depression anxiety etc)
Understanding functional genomics (in terms of mice)
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
Broad areas animal models are widely used in?
Behavioural neuroscience - what part of the brain does what
psychopharmacology - assessing acute and long-term effects of drugs
What did THC (canabis) change about the behaviour of the rat?
Very still, indifferent, bit more anxious
Describe the hotplate test and what it allows
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.
Does the hot plate cause tissue damage to the rat?
No but in experimental conditions has potential to
Describe the bar test and what it tests
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.
What is catalepsy?
A characteristic waxy immobility that is seen
in rats after high doses of specific drugs.
What drugs cause catalepsy in rats?
Opiods, Bemps, Cannaborids
Describe the elevated plus maze and what it tests
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
gat does anxiolytic drug lead to in plus maze?
Less anxiety, more ok with it
Problems with testing alcohol on plus maze
Might fall off or be immobile
What is the brand name of chlordiazepoxide?
Librium
What is stereotypy?
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
What often causes stereotypy?
Behavioural and neurochemical sensitisation
Describe the effects of high dose amphetamine on behaviour
Heightened stereotypy behaviour
What kind of drug can be given to block stereotypy induced by amphetamine?
Dopamine antagonist, Fluphefarmine
What was the difference between pure THC and THC+cannabidiol?
THC: Highly anxious, suspicious
THC + Cannbidiol: happy, relaxed
Effects of smoking high THC level marijuana
More depressive, anxious state
however really depends on the person - higher for those with predisposition for scrutiny
Benefits of conducting research into psychoactive drugs on human volunteers?
Real time info
Descriptive understanding
More valid
Limitations of conducting research into psychoactive drugs on human volunteers?
Ethical issues
Quite subjective
Not as much control over prior factors
4 major ways drugs can alter neurotransmission:
- Increasing neurotransmitter release from vesicles
- Inhibition or reversal of transporter proteins
- Inhibiting neurotransmitter degradation
- Directly binding to receptors
Increasing neurotransmitter release from vesicles
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
Inhibition or reversal of transporter proteins
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
Define reuptake
Transporter proteins ferry the neurotransmitter back from the synapse into the terminal, for repackaging into vesicles
2 purposes of reuptake
(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).
What is monomine oxidase (MAO) and what two forms is it present in?
Important enzyme with respect to drugs of abuse
MAO-A, which preferentially metabolises serotonin, and
MAO-B, which preferentially
metabolises dopamine
Inhibiting neurotransmitter degradation
By inhibiting MAO, the affected neurotransmitter will remain in the synapse
for longer, thereby prolonging its action at its receptors.
Directly binding to receptors
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
Ecstasy:
- Name two neurotransmitter systems that it acts on.
- Positive and negative effects
- In which two ways does MDMA interact with serotonin
- How might MDMA precipitate depression in heavy or chronic users?
- Serotonin, moradrenaline
- 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)
- 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 - 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.
Speed
- Which neurotransmitter systems does amphetamine affect?
- Name 3 mechanisms through which it affects these neurotransmitters.
- What physiological effects does amphetamine produce?
- Dopamine and noradrenaliine (both involved in transporting information between neurons
- 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 - Can arouse pleasure and euphoria and make you feel energetic
Cocaine
- What are the effects?
- Describe 2 ways in which cocaine increases dopamine release
- Intensifies release of dopamine
- 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.
Cannabis:
- Effects
- What neurotransmitter does THC mimic?
- How does THC indirectly stimulate the release of dopamine n the nucleus accumbens?
- % of dependent users, why it is less addictive
- 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
1/ relaxed, contented and slightly intoxacted, coordination problems, impairment of memory
- Anandamide (binds to receptors)
- Indirect, through GABA (inhibits excessive release of dopamine), interferes with GABA so more dopamine is released
- 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
Herion:
1. 3 effects
- name an endogenous opiate
- Explain how opiates indirectly stimulate dopamine release
- Why can heroin overdose lead to suffocation?
- pleasure, pain relief and suppression of breathing
- Morphine
- Inhibits GABA release, slower to breakdown and dopamine persists
b) also binds to dopamine but can’t keep it under control - 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.
Alcohol:
- 5 neurotransmitter systems
- Effects of increased GABA release
- How does it interact with GABA receptors
- Effect on cerebellum (high density GABA)
- the neural mechanism that underpins alcohol tolerance?
- Symptoms of alcohol withdrawal
- dopamine, serotonin, endorphin, GABA and glutamate.
- GABA has an inhibitory effect on other neurons, and thus causes certain parts of the brain to work more slowly.
- 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
- Alcohol reduces your fine motor control, because your cerebellum slows down.
- 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.
- Insomnia, jitteriness, sweating, anxiety and depression
