Neuropharmacology Flashcards
(181 cards)
1
Q
how many neurons in the brain?
A
100 billion
2
Q
how many synapses in the cortex?
A
0.15 quadrillion
3
Q
what are the two types of receptors?
A
ion channels and g protein coupled receptor
4
Q
how do ion channels function? and what do they allow?
A
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
5
Q
how do g protein coupled receptors work?
A
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)
6
Q
what is the main difference between a NT and neuromodulator
A
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
7
Q
can the same molecule act as both a NT and NM?
A
yes
8
Q
in regards to NT and NM, what is the currency, and what is the gov/police?
A
NT’s are currency (excitatory or inhibitory)
NMs are more the police (serotonin, dopamine, noradrenaline etc)
9
Q
which is excitatory, which is inhibitory out of glutmate and gaba?
A
glutamate = excitatory gaba = inhibitory
10
Q
NMs alter what at the pre-synapse? they alter what at the post synapse?
A
pre: NT release
post: NT action (excitability/firing pattern)
11
Q
for drugs to have an effect, what do they HAVE to do?
A
dock onto a receptor
12
Q
how do drugs have an effect on receptors?
A
they mimick natural NTs or NMs
13
Q
drugs acting as agonists do what?
A
activate the receptor like the natural compound does
14
Q
drugs acting as antagonists do what?
A
block the receptor and prevent the natural compound from activating the receptor
15
Q
is the process from synthesis to NT action slow or fast ?
A
the synthesis is thought to be slow, but the NT action is very fast as it is sitting, waiting for release
16
Q
what are the most common NTs in the CNS?
A
Glutamate and GABA
17
Q
what makes ‘true’ NT?
A
directly affecting the likelihood of the post synaptic Neuron firing
18
Q
what is released by ALL excitatory neurons?
A
Glutamate
19
Q
estimated that over half of all brain synapses release what?
A
glutamate
20
Q
what actually is glutamate?
A
glutamic acid
21
Q
is glutamate used as a NT in its raw form?
A
yes
22
Q
is glutamate an amino acid?
A
yes
23
Q
why does glutamate as an amino acid still need to be synthesised in the brain despite it already being a NT?
A
because this amino acid cannot pass through the blood barrier
24
Q
what is glutamate synthesised from?
A
glutamine
25
T or false, excitatory connections are not point to point.
false
26
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
27
how many different binding sites are on the NMDA receptor?
6.
28
what is glycine?
an amino acid
29
if the NMDA receptor is open, what channel does it open, allowing what to flow through it?
calcium channel
| Ca2+
30
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
31
alcohol is what an an NMDA receptor? resulting in?
antagonist, resulting in the NMDA receptor being blocked
32
reduction on glutamate as a result of alcohol is believed to contribute to what?
general sedative effects and memory effects
33
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
34
which two drugs in addition to alcohol affect NMDA receptors? are they antagonists or agonists?
Phencyclidine (PCP) and ketamine
35
both ketamine and PCP cause what?
dissociative hallucinations
36
what are dissociative hallucinations?
people feel disconnected, but do not have "sensory overload" like other hallucinogens do
37
can ketamine kill someone?
no, it does not harm the actual body, but there is a risk of suicidal behaviour
38
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
39
what is the percentage of population experiencing psychosis?
around 3%
40
is there a link between glutamate and psychosis?
some have suggested a link but there is much more to it
41
what does NMDA-R encephalitis involve?
inflammation of the brain caused by autoimmune response to NMDA receptors
42
NMDA receptor is crucial for what?
learning, memory, perception and synaptic plasticity in general
43
what have large schizophrenia studies identified?
likely that the NMDA receptor gene is likely relevant to dev of schizophrenia
44
what is the primary inhibitory NT?
GABA
45
what does gaba stand for?
gamma - amino - butyric - acid
46
what does GABA do?
decreases likelihood of post synaptic neuron firing
47
what is the importance of GABA and inhibitory NTs
keeps the brain under wraps, otherwise there would be constant firing which is bad (seizures)
48
How does gaba help neurons fire?
it plays important role in the selectivity of neurons firing
49
what is GABA produced from
glutamic acid
50
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)
51
how many people in Aus experience seizure disorders?
400,000
52
what is a generalised seizure?
a seizure that is widespread and involves most of the brain
53
what is a partial seizure?
seizure that is restricted to small part of the brain
54
what is a complex seizure?
a seizure where the individual loses consciousness
55
what is a simple seizure?
a seizure where changes in consciousness can happen, but no loss in consciousness takes place
56
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
57
what are the two main nuclei responsible for the synthesis and release of dopamine?
```
substantia nigra (SN)
ventral tegmental area (VTA)
```
58
T or F?
| the substantia nigra and the ventral tegemental area can release both dopamine and another NT?
false
59
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
60
what is tryrosine hydroxylase?
it is a synthesis enzyme for tryrosine
61
what does Tryrosine Hydroxylase turn tryrosine in to?
DOPA
62
what synthesis enzyme turns DOPE into dopamine?
Amino acid decarboxylase
63
if dopamine is synthesised by dopamine beta-hydroxylase, what does it become?
noradrenaline
64
what are the three variations of elements in the dopamine synthesis?
Tryrosine
DOPA
dopamine
65
What is L-DOPA ? what does it do?
a synthetic version of DOPA that can be synthesised to Dopeamine
66
what is the cause of parkinson's?
death of dopamine cells in substantia nigra
67
what are symptoms of parkinson's?
motor tremor, cog impairments, dementia and overall reduced exec. function
68
what are some potential side effects of receiving treatment for parkinson's?
impulsively, gambling, hyper-sexuality
69
what is the use of reward prediction error
provides us with explanation of how dopamine works
70
what does dopamine actually code?
not the reward itself, but rather the expectation or unexpectedness of the reward
71
what are "real" rewards
food and sex
72
what are "symbolic" rewards?
money
73
what are "virtual" rewards?
points in a game
74
in gambling, what adds to the boost of dopamine?
the unpredictability of it
75
how is drug addiction defined?
a chronic relapsing disorder which consists of compulsive pattern of drug seeking and drug taking behaviour
76
what are two key things that make an "addiction"
- takes place at expense of other activities
| - persists despite adverse consequences
77
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
78
what are the two main dopamine drugs
cocaine and amphetamine
79
what are the two types of amphetamine drugs? which is more pure
ice and speed
| ice is most pure and speed is less pure
80
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
81
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
82
what influences how addictive dopamine drugs are ?
the faster the DA release, the more addictive
83
in dopamine drugs, what influences the greatness of the high experienced?
the amount of DA released
84
what are the 2 "problems" of how addiction takes place?
| what is the result?
1. drugs initiate "wanting"
2. 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
85
what is the more common name for methylphenidate?
Ritalin
86
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
87
what is the base amino acid for noradrenaline?
Tryrosine
88
what does the enzyme monoamine oxidase do?
breaks noradrenaline down to an inactive metabolite, thus ending the stream of the dopamine and noradrenaline
89
if noradrenaline undergoes one more synthesis step in the adrenal glands what is released?
the hormone adrenaline is produced
90
noradrenaline is generated from... ?
the locus coeruleus
91
how many neurons does the locus coeruleus contain?
around 30,000
92
what is norepinephrine ?
exact same thing as noradrenaline
93
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
94
what are the 4 f's?
Fight, flight freeze fornicate
95
what can sustained LC/NA activity lead to?
stress
| anxiety
96
what can inappropriate spikes in LC/NA lead to?
panic attacks
97
how long do symptoms have to show for for anxiety to be diagnosed?
6 months
98
at moderate levels of LC activity, what does noradrenaline do ?
acts to consolidate decisions
99
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
100
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
101
what influences how big a noradrenaline burst is?
how salient the stimulus is
102
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
103
pupil dilation reflects what?
activity in the LC
104
pupil constriction is driven by..
ACh
105
t or F... there is a pupil dilation at the time of the switch during perceptual rivalries
True
106
is noradrenaline involved only in motor decisions? or cognitive/internal decisions as well? what study showed this?
both
| rock paper scissors dilation study
107
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
108
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
109
what is 5-hydroxytryptamine (5-HT)?
serotonin
110
is serotonin (5-HT) a neuro modulator or NT ?
NM
111
reduction in serotonin can lead to?
sadness, depressed states
112
neurons that release and synthesise serotonin are located in the....
raphe nucleus
113
what does "raphe" mean
midline
114
True or false, serotonin has many receptor subtypes
true
115
how does the one compound (serotonin) affect various things like temperature function, appetite regulation etc
because of all the different types of receptor subtypes
116
true or false, drugs often activate lots of receptor subtypes
false, they are often more selective
117
what is tryptophan? where is it found?
an amino acid found in cheese, chicken and chocolate
118
what is the amino acid required for serotonin?
tryptophan
119
what is the name of the enzyme that synthesises tryptophan to form serotonin?
tryptophan hydroxylase (TPH)
120
monoamine oxidase breaks down what compounds?
serotonin, dopamine and noradrenaline
121
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?
122
what was removed in DSM-5 as a symptom of depression?
grief/bereavement
123
what are the percentages of men and women who will experience depression?
women; 10-25%
| men: 5-12%
124
how much is depression estimated to cost aus in health care a year?
over 15 billion
125
when does 1st onset of depression often occur?
around 15 to 18 years old
126
PET studies show what?
receptor bindings
127
what have PET studies showed regarding depression
serotonin receptors are relatively reduced in depressed patients
128
a gene involved in transportation of serotonin is linked to what?
increased risk of developing depression
129
how are serotonin and stress related?
serotonin function is important in managing the feedback control of the brain's stress response
130
how much more likely is depression after a stressful event?
5-6x
131
what are some serotonin anti depressant drugs?
citalopram, fluoxetine, paroxetine, sertraline
132
what are SSRI's?
selective serotonin re-uptake inhibitors (serotonin antidepressants)
133
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
134
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
135
what does long latency onset describe?
it describes why it takes SSRIs a relatively long amount of time to take effect
136
True or false, SSRIs can promote new brain cell growth
true
137
despite SSRIs promoting new brain cell growth, they do not offer any neuro protective benefits, t or f?
false
138
in healthy people, what has prozac been seen to do?
increase empathy and prosocial behaviour
139
what do monoamine oxidase inhibitors do? what is the result?
blocks the breakdown of serotonin.
| there is more serotonin in the persons system
140
what does cheese syndrome involve
potential cause of death due to eating foods with high tryptophan amounts, leading to lethal levels of serotonin
141
what are the 4 non traditional NTs?
peptides, nucleoids, lipids and gases
142
what do peptides consist of?
2 or more amino acids
143
how are peptides "synthesised"?
they are not traditionally synthesised, as they are actually broken down from larger compounds (poly - peptides)
144
are peptides NMs, or hormones acting as NTs?
they can be both in different circumstances
145
what is the most commonly known family of peptide NTs
endogenous opioids
146
areas where the highest density of opiate receptors are located are associated with what?
pain reception
147
what does endogenous opioid mean?
something occurring internally in the brain that is like opium
148
what does opiate mean?
artificial sources of opium including morphine, heroin, and opium
149
how can heroin affect health/cause death?
through respritory failure, but is not neurotoxic
150
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
151
what are 3 heroin dependency treatment drugs
Buprenorphine , naloxone, methadone
152
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
153
how does naloxone treat heroine dependence?
is a full antagonist, thus rapidly blocking heroin receptors
154
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
155
what are lipids?
naturally occurring molecules like fats and waxes
156
lipds are hydrophobic, what does this mean?
they fear water
157
what are the main biological function of lipids?
energy storage and structural components of cell membranes
158
what are the best known lipid NTs?
endocannabinoids
159
what are the 2 known cannabinoid receptors?
CB1 and CB2
160
where do CB1 receptors sit?
on the pre-synaptic neuron
161
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
162
regulating CB1 receptors serve to...
modulate the modulators
163
what is the active compound in marijuana?
THC (tetrahydrocannabinol)
164
what are some effects from consuming THC/marijuana
changes in appetite, time perception, "underachievement"
165
therapeutically, what does THS/marijuana offer?
reduce nausea, relieves asthma attacks, decreases pressure in the eyes in glucoma
166
what are nucleic acids?
the hereditary controlling parts of all living cells eg dna and rna
167
what are nucelosides? how are they obtained?
a subunit of nucleic acids
| by chemical/enzymatic breakdown
168
true or false, nucleosides are also modulators to the modulators?
true
169
what is an example of nucleoside?
adenosine
170
is adenosine an inhibitory or excitatory NT?
inhibitory
171
adenosine forms from the breakdown of what?
adenosine triphosphate (ATP)?
172
ATP is responsible for what?
is primary energy source in cells for transport systems and enzymes
173
high postsynaptic firing rate where adenosine is the primary NT leads to what ?
increased sleepiness and supreses arousal throughout the day
174
drugs that are relevant to countering adenosine is...
caffeine
175
how does caffeine work to counter adenosine?
it acts as a receptor antagonist, blocking adenosine receptors
176
what is a soluble gas ?
gases that dissolve in fluid
177
which two gases are used as NTs in the brain?
nitric oxide, and carbon monoxide
178
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
179
what amino acid is nitric oxide produced from? by how many neurons?
arginine
| subpopulation of 1-2% of neurons in the cortex
180
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
181
how do NMs actually modulate?
they modulate the function or sensitivity of pre and post synaptic in slower and more global signals
