Neuropharmacology Flashcards
how many neurons in the brain?
100 billion
how many synapses in the cortex?
0.15 quadrillion
what are the two types of receptors?
ion channels and g protein coupled receptor
how do ion channels function? and what do they allow?
NT attaches to receptor which then opens the gate of the ion channel, and only allows selective ions to flow through, eg, calcium channel only allows calcium ions to flow through
how do g protein coupled receptors work?
NT binds to this receptor that activates second messenger system that can open a channel or cause other changes to take place in the cell, (eg, dna being transcribed and new proteins being made)
what is the main difference between a NT and neuromodulator
serving the function of being released at a anatomically specialised location to have localised and specific effect, while NM are sort of a bit more all over the place
can the same molecule act as both a NT and NM?
yes
in regards to NT and NM, what is the currency, and what is the gov/police?
NT’s are currency (excitatory or inhibitory)
NMs are more the police (serotonin, dopamine, noradrenaline etc)
which is excitatory, which is inhibitory out of glutmate and gaba?
glutamate = excitatory gaba = inhibitory
NMs alter what at the pre-synapse? they alter what at the post synapse?
pre: NT release
post: NT action (excitability/firing pattern)
for drugs to have an effect, what do they HAVE to do?
dock onto a receptor
how do drugs have an effect on receptors?
they mimick natural NTs or NMs
drugs acting as agonists do what?
activate the receptor like the natural compound does
drugs acting as antagonists do what?
block the receptor and prevent the natural compound from activating the receptor
is the process from synthesis to NT action slow or fast ?
the synthesis is thought to be slow, but the NT action is very fast as it is sitting, waiting for release
what are the most common NTs in the CNS?
Glutamate and GABA
what makes ‘true’ NT?
directly affecting the likelihood of the post synaptic Neuron firing
what is released by ALL excitatory neurons?
Glutamate
estimated that over half of all brain synapses release what?
glutamate
what actually is glutamate?
glutamic acid
is glutamate used as a NT in its raw form?
yes
is glutamate an amino acid?
yes
why does glutamate as an amino acid still need to be synthesised in the brain despite it already being a NT?
because this amino acid cannot pass through the blood barrier
what is glutamate synthesised from?
glutamine
T or false, excitatory connections are not point to point.
false
how many glutamate receptors are there? what are they all called?
specify which are ion channels (ionotropic) and which are g protein coupled (metabotropic)
4 ion channels NMDA receptor AMPA receptor Kainate Receptor
g protein coupled
metabotropic glutamate
how many different binding sites are on the NMDA receptor?
6.
what is glycine?
an amino acid
if the NMDA receptor is open, what channel does it open, allowing what to flow through it?
calcium channel
Ca2+
the NMDA receptor only works if what molecule is attached?
and if what is not bound to the inside?
glycine
magnesium cannot be bound to the inside
alcohol is what an an NMDA receptor? resulting in?
antagonist, resulting in the NMDA receptor being blocked
reduction on glutamate as a result of alcohol is believed to contribute to what?
general sedative effects and memory effects
while alcohol is an NMDA antagonist, what is it also?
what does this lead to?
it is also an agonist for GABA
further brain inhibition
which two drugs in addition to alcohol affect NMDA receptors? are they antagonists or agonists?
Phencyclidine (PCP) and ketamine
both ketamine and PCP cause what?
dissociative hallucinations
what are dissociative hallucinations?
people feel disconnected, but do not have “sensory overload” like other hallucinogens do
can ketamine kill someone?
no, it does not harm the actual body, but there is a risk of suicidal behaviour
what is psychosis? what are the symptoms of it?
not a diagnosis, but a cluster of symptoms
- delusions
- hallucinations
- depression
- anxiety
- suicidal thoughts or actions
- disorganised speech
what is the percentage of population experiencing psychosis?
around 3%
is there a link between glutamate and psychosis?
some have suggested a link but there is much more to it
what does NMDA-R encephalitis involve?
inflammation of the brain caused by autoimmune response to NMDA receptors
NMDA receptor is crucial for what?
learning, memory, perception and synaptic plasticity in general
what have large schizophrenia studies identified?
likely that the NMDA receptor gene is likely relevant to dev of schizophrenia
what is the primary inhibitory NT?
GABA
what does gaba stand for?
gamma - amino - butyric - acid
what does GABA do?
decreases likelihood of post synaptic neuron firing
what is the importance of GABA and inhibitory NTs
keeps the brain under wraps, otherwise there would be constant firing which is bad (seizures)
How does gaba help neurons fire?
it plays important role in the selectivity of neurons firing
what is GABA produced from
glutamic acid
how many types of gaba receptors are there? what are they called and what type of receptor are they?
2
GABA a receptor (ion channels)
GABA b receptor (g protein coupled)
how many people in Aus experience seizure disorders?
400,000
what is a generalised seizure?
a seizure that is widespread and involves most of the brain
what is a partial seizure?
seizure that is restricted to small part of the brain
what is a complex seizure?
a seizure where the individual loses consciousness
what is a simple seizure?
a seizure where changes in consciousness can happen, but no loss in consciousness takes place
the majority of genes that have been found to be involved in seizures are linked to what?
ion channels, thus influencing the level of positive or negative charge in the brain that drive action potentials
what are the two main nuclei responsible for the synthesis and release of dopamine?
substantia nigra (SN) ventral tegmental area (VTA)
T or F?
the substantia nigra and the ventral tegemental area can release both dopamine and another NT?
false
what is tryrosine? where is it found? what is it/what does it do?
amino acid
found in food
it is the building block of dopamine
what is tryrosine hydroxylase?
it is a synthesis enzyme for tryrosine
what does Tryrosine Hydroxylase turn tryrosine in to?
DOPA
what synthesis enzyme turns DOPE into dopamine?
Amino acid decarboxylase
if dopamine is synthesised by dopamine beta-hydroxylase, what does it become?
noradrenaline
what are the three variations of elements in the dopamine synthesis?
Tryrosine
DOPA
dopamine
What is L-DOPA ? what does it do?
a synthetic version of DOPA that can be synthesised to Dopeamine
what is the cause of parkinson’s?
death of dopamine cells in substantia nigra
what are symptoms of parkinson’s?
motor tremor, cog impairments, dementia and overall reduced exec. function
what are some potential side effects of receiving treatment for parkinson’s?
impulsively, gambling, hyper-sexuality
what is the use of reward prediction error
provides us with explanation of how dopamine works
what does dopamine actually code?
not the reward itself, but rather the expectation or unexpectedness of the reward
what are “real” rewards
food and sex
what are “symbolic” rewards?
money
what are “virtual” rewards?
points in a game
in gambling, what adds to the boost of dopamine?
the unpredictability of it
how is drug addiction defined?
a chronic relapsing disorder which consists of compulsive pattern of drug seeking and drug taking behaviour
what are two key things that make an “addiction”
- takes place at expense of other activities
- persists despite adverse consequences
what does cocaine do to dopamine release? what is the result?
blocks the re-uptake of dopamine transmitters after they have been released from the pre synaptic neuron, thus increasing the dopamine signal as more dopamine NTs are left in the synapse
what are the two main dopamine drugs
cocaine and amphetamine
what are the two types of amphetamine drugs? which is more pure
ice and speed
ice is most pure and speed is less pure
what do amphetamines do to dopamine release, what is the result?
they reverse the re-uptake of dopamine NTs, resulting in even more dopamine being released into the synapse compared to simply blocking the re-uptake
how do addictive drugs “hijack” the reward response?
because the drug releases dopamine, these drugs are coded by the brain as even better than expected
what influences how addictive dopamine drugs are ?
the faster the DA release, the more addictive
in dopamine drugs, what influences the greatness of the high experienced?
the amount of DA released
what are the 2 “problems” of how addiction takes place?
what is the result?
- drugs initiate “wanting”
- cognitive (top down) processing is reduced by impaired function of the prefrontal cortex, which is caused by excessive dopamine
loss of top down control contributes to loss of control over urge to take drugs
what is the more common name for methylphenidate?
Ritalin
what does Ritalin do in the brain? what is it used to treat?
it inhibits the re-uptake of dopamine and noradrenaline and is a treatment for ADHD
what is the base amino acid for noradrenaline?
Tryrosine
what does the enzyme monoamine oxidase do?
breaks noradrenaline down to an inactive metabolite, thus ending the stream of the dopamine and noradrenaline
if noradrenaline undergoes one more synthesis step in the adrenal glands what is released?
the hormone adrenaline is produced
noradrenaline is generated from… ?
the locus coeruleus
how many neurons does the locus coeruleus contain?
around 30,000
what is norepinephrine ?
exact same thing as noradrenaline
when do neurons in the LC fire?
when are they practically ‘silent’?
during highly aroused situations, eg transient noxious event or extremely positive stimulus
- during REM sleep
what are the 4 f’s?
Fight, flight freeze fornicate
what can sustained LC/NA activity lead to?
stress
anxiety
what can inappropriate spikes in LC/NA lead to?
panic attacks
how long do symptoms have to show for for anxiety to be diagnosed?
6 months
at moderate levels of LC activity, what does noradrenaline do ?
acts to consolidate decisions
what is the overall theory that aims to describe noradrenaline’s existence? how does it do this?
buys the brain a few seconds to actually act on the decisions that are made. it essentially shuts down the competing alternatives, so decisions are not changed immediately
what seems to happen with noradrenaline in the LC after every decision? what does this allow?
neurons fire after every decision, when a behavioural response is selected and executed
this is followed by a period where those neurons are inhibited
this allows the selected behaviour to be exploited
what influences how big a noradrenaline burst is?
how salient the stimulus is
what happens in the absence of a burst of firing of noradrenaline?
the baseline levels of firing of NA increase, and there is a gradual build up of NA throughout the brain
pupil dilation reflects what?
activity in the LC
pupil constriction is driven by..
ACh
t or F… there is a pupil dilation at the time of the switch during perceptual rivalries
True
is noradrenaline involved only in motor decisions? or cognitive/internal decisions as well? what study showed this?
both
rock paper scissors dilation study
what is locked in syndrome?
a stroke in deeper regions of the brain where the person is completely paralysed, but have relatively normal brain functioning
T or F? NA and the LC play different roles in perceptual/cognitive decisions, and behaviour like optimising a balance between exploitation and stability?
False
what is 5-hydroxytryptamine (5-HT)?
serotonin
is serotonin (5-HT) a neuro modulator or NT ?
NM
reduction in serotonin can lead to?
sadness, depressed states
neurons that release and synthesise serotonin are located in the….
raphe nucleus
what does “raphe” mean
midline
True or false, serotonin has many receptor subtypes
true
how does the one compound (serotonin) affect various things like temperature function, appetite regulation etc
because of all the different types of receptor subtypes
true or false, drugs often activate lots of receptor subtypes
false, they are often more selective
what is tryptophan? where is it found?
an amino acid found in cheese, chicken and chocolate
what is the amino acid required for serotonin?
tryptophan
what is the name of the enzyme that synthesises tryptophan to form serotonin?
tryptophan hydroxylase (TPH)
monoamine oxidase breaks down what compounds?
serotonin, dopamine and noradrenaline
what are the requirements according to DSM-V to diagnose depression
5 of the 9 symptoms
persisting over 2 week period
at least one of the symptoms is depressed mood or loss of interest/pleasure?
what was removed in DSM-5 as a symptom of depression?
grief/bereavement
what are the percentages of men and women who will experience depression?
women; 10-25%
men: 5-12%
how much is depression estimated to cost aus in health care a year?
over 15 billion
when does 1st onset of depression often occur?
around 15 to 18 years old
PET studies show what?
receptor bindings
what have PET studies showed regarding depression
serotonin receptors are relatively reduced in depressed patients
a gene involved in transportation of serotonin is linked to what?
increased risk of developing depression
how are serotonin and stress related?
serotonin function is important in managing the feedback control of the brain’s stress response
how much more likely is depression after a stressful event?
5-6x
what are some serotonin anti depressant drugs?
citalopram, fluoxetine, paroxetine, sertraline
what are SSRI’s?
selective serotonin re-uptake inhibitors (serotonin antidepressants)
how do SSRI’s work?
they selectively block the re-uptake of serotonin, meaning that there are more serotonin NM’s in the synapse, allowing for more NM’s to attach to receptors
how long does it take for SSRIs to cause therapeutic effects? how long does it take for these to reach the brain if they are taken orally?
often takes weeks, but reaches the brain after approx. 1 hour
what does long latency onset describe?
it describes why it takes SSRIs a relatively long amount of time to take effect
True or false, SSRIs can promote new brain cell growth
true
despite SSRIs promoting new brain cell growth, they do not offer any neuro protective benefits, t or f?
false
in healthy people, what has prozac been seen to do?
increase empathy and prosocial behaviour
what do monoamine oxidase inhibitors do? what is the result?
blocks the breakdown of serotonin.
there is more serotonin in the persons system
what does cheese syndrome involve
potential cause of death due to eating foods with high tryptophan amounts, leading to lethal levels of serotonin
what are the 4 non traditional NTs?
peptides, nucleoids, lipids and gases
what do peptides consist of?
2 or more amino acids
how are peptides “synthesised”?
they are not traditionally synthesised, as they are actually broken down from larger compounds (poly - peptides)
are peptides NMs, or hormones acting as NTs?
they can be both in different circumstances
what is the most commonly known family of peptide NTs
endogenous opioids
areas where the highest density of opiate receptors are located are associated with what?
pain reception
what does endogenous opioid mean?
something occurring internally in the brain that is like opium
what does opiate mean?
artificial sources of opium including morphine, heroin, and opium
how can heroin affect health/cause death?
through respritory failure, but is not neurotoxic
how does heroin act in the brain? what is the result?
it is a full agonist, therefore attaching to receptors the same way as a natural compound would
what are 3 heroin dependency treatment drugs
Buprenorphine , naloxone, methadone
how does Buprenorphine treat heroine dependence?
it is a partial agonist. it has the same affect as heroin but nowhere near as much, thus, it blocks the affect of heroin on the receptors and blunts the impact of the drug
how does naloxone treat heroine dependence?
is a full antagonist, thus rapidly blocking heroin receptors
how does methadone treat heroine dependence?
it is also a full agonist, but has a much smaller time course than heroin, as such has a more controlled/stable effect
what are lipids?
naturally occurring molecules like fats and waxes
lipds are hydrophobic, what does this mean?
they fear water
what are the main biological function of lipids?
energy storage and structural components of cell membranes
what are the best known lipid NTs?
endocannabinoids
what are the 2 known cannabinoid receptors?
CB1 and CB2
where do CB1 receptors sit?
on the pre-synaptic neuron
activation of the CB1 receptor does what ? what is the effect?
it shortens the duration of the action potentials in the pre-synaptic neuron, decreasing amount of released NTs
regulating CB1 receptors serve to…
modulate the modulators
what is the active compound in marijuana?
THC (tetrahydrocannabinol)
what are some effects from consuming THC/marijuana
changes in appetite, time perception, “underachievement”
therapeutically, what does THS/marijuana offer?
reduce nausea, relieves asthma attacks, decreases pressure in the eyes in glucoma
what are nucleic acids?
the hereditary controlling parts of all living cells eg dna and rna
what are nucelosides? how are they obtained?
a subunit of nucleic acids
by chemical/enzymatic breakdown
true or false, nucleosides are also modulators to the modulators?
true
what is an example of nucleoside?
adenosine
is adenosine an inhibitory or excitatory NT?
inhibitory
adenosine forms from the breakdown of what?
adenosine triphosphate (ATP)?
ATP is responsible for what?
is primary energy source in cells for transport systems and enzymes
high postsynaptic firing rate where adenosine is the primary NT leads to what ?
increased sleepiness and supreses arousal throughout the day
drugs that are relevant to countering adenosine is…
caffeine
how does caffeine work to counter adenosine?
it acts as a receptor antagonist, blocking adenosine receptors
what is a soluble gas ?
gases that dissolve in fluid
which two gases are used as NTs in the brain?
nitric oxide, and carbon monoxide
what is nitric oxide in the cardiovascular system? that can do what?
a signalling molecule
it dilates blood vessels, which can increase blood flow to various areas of the brain
what amino acid is nitric oxide produced from? by how many neurons?
arginine
subpopulation of 1-2% of neurons in the cortex
how is nitric oxide very different to traditional NTs
list 3 reasons
- not synthesised and stored in vesicles
- NO is produced all throughout the cell and simply defuses out of the cell
- it does not activate receptors on the next cell, but simply enters it
how do NMs actually modulate?
they modulate the function or sensitivity of pre and post synaptic in slower and more global signals
