19. Principles of Neuronal Function (2) Flashcards

Question 1

Q

Summarise the evolution and ultimate function of the brain.

Answer

A

Nervous systems evolved to allow predictive interactions between mobile animals and their environment.
To move around safely, an animal must anticipate the outcome of each movement on the basis of incoming sensory data.
Prediction may thus be the ultimate function of the brain.

Question 2

Q

Who discovered chemical transmission at synapses?

Answer

A

Henry Dale and Otto Loewi

Question 3

Q

Give some experimental evidence for chemical transmission at a synapse.

[EXTRA]

Answer

A

Dale and Loewi’s experiment:

Stimulation of a heart by the vagus caused it to contract more slowly
When the fluid medium from the first heart was transferred to a different heart, this one also slowed down
This suggested that there was some substance secreted by the vagus nerve (in this case, ACh)

Question 4

Q

How many synapses are there in the brain?

Answer

A

1-5 x 10¹⁴

Question 5

Q

What are some common disorders due to abnormal functioning of synaptic transmission in the CNS?

Answer

A

Anxiety
Depression
Schizophrenia
Epilepsy
Alzheimer’s disease
Parkinson’s disease
Huntington’s disease
Migraine

Question 6

Q

What are the main classes of neurotransmitter in the CNS?

Answer

A

Amino acids
Acetylcholine
Monoamines
Peptides [EXTRA]
Gaseous [EXTRA]
Miscellaneous [EXTRA]

Question 7

Q

What are some examples of amino acid neurotransmitters in the CNS?

Answer

A

GABA
Glutamate
Glycine

Question 8

Q

What are some examples of monoamines neurotransmitters in the CNS?

Answer

A

Catecholamines (noradrenaline, dopamine)
Indoleamines (5-hydroxtryptamine a.k.a. serotonin)
Others (melatonin, histamine)

Question 9

Q

What are some examples of peptide neurotransmitters in the CNS? [EXTRA]

Answer

A

Hypothalamic releasing factors (eg. somatostatin)
Tachykinins (eg. Substance P)
Opioids (eg. enkephalins)
Others (eg. CCK, NPY, orexin)

Question 10

Q

What are some examples of gaseous neurotransmitters in the CNS? [EXTRA]

Question 11

Q

What are some examples of miscellaneous neurotransmitters in the CNS? [EXTRA]

Answer

A

Purines
Endocannabinoids

Question 12

Q

Describe the different types of neurons in the cerebral cortex.

Answer

A

Interlaminar neurons (glutamate or GABA) -> These span between the layers of the cortex
Local circuit neurons (GABA, peptides or gaseous) -> These are interneurons that have a limited sphere of influence
Cortico-cortical neurons (glutamate) -> Connect different parts of the cortex
Cortico-subcortical neurons (glutamate) -> Provide all output from the brain to the subcortical regions

Also:

Receive fibres from neurons in the brainstem (monoamine and ACh)

Question 13

Q

Describe the different types of neurons in the subcortical regions of the brain (cerebellum, striatum, thalamus, spinal cord).

Answer

A

Local circuit neurons (GABA and peptides) -> These are interneurons that have a limited sphere of influence
Projecting neurons (GABA and peptides) -> These project out of the brain to more distant regions of the CNS

Also:

Receive fibres from neurons in the brainstem (monoamine and ACh)
Receive fibres from cortico-subcortical neurons in the cerebral cortex (glutamate)

Question 14

Q

Describe the different types of neurons in the brainstem.

Answer

A

Neurons that output to the cerebral cortex and subcortical regions (monoamine and ACh)

Question 15

Q

Approximately what percentage of neurons in the brain are utilising these neurotransmitters:

Glutamate
GABA
Other

Answer

A

Glutamate -> 60%
GABA -> 30%
Other -> 10%

Question 16

Q

What are some criteria for proving that something is a neurotransmitter in a neuron?

[IMPORTANT]

Answer

A

Neuronal localisation
Neuronal release
Synaptic mimicry

It is also important to distinguish between whether it is a neurotransmitter or neuromodulator.

Question 17

Q

How can neuronal localisation be used to show that something is a neurotransmitter in a neuron?

Answer

A

Should be able to find one or more of these within or near the neuron:
- NT itself
- Enzymes used to make it
- Reuptake mechanisms
- Receptors for it
These can be tested for using immunocytochemistry

Question 18

Q

How can neuronal release be used to show that something is a neurotransmitter in a neuron?

Answer

A

The neuron itself should release the neurotransmitter
This can be done by incubating the neuron is a medium and then sampling the supernatant for neurotransmitter levels

Question 19

Q

How can synaptic mimicry be used to show that something is a neurotransmitter in a neuron?

Answer

A

If exogenous neurotransmitter or an agonist of its receptor are applied to the target neuron, you should see the same physiological response as with stimulation by the pre-synaptic neuron.

Question 20

Q

Compare a neurotransmitter and neuromodulator.

[EXTRA]

Answer

A

Neurotransmitter:

Acts directly on a postsynaptic neuron to cause a change in its membrane potential, although it may sometimes act through second messengers.

Neuromodulator:

Affects groups of neurons, or effector cells that have the appropriate receptors.
It may not be released at synaptic sites
Often acts through second messengers and can produce long-lasting effects.
Does not necessarily carry excitation of inhibition from one neuron to another, but instead alters either the cellular or synaptic properties of certain neurons so that neurotransmission between them is changed

Question 21

Q

What are some techniques that are used to understand the function of a neurotransmitter?

Answer

A

Transmitter pathway mapping
- Localisation of where the NT is found
- Pathway tracing of where the neurons are positioned
Transmitter pathway lesion (in a test animal)
- Mechanically or electrolytic lesion
- Neurotoxin lesion against specific types of neurons
Pharmacological manipulation
- Use of agonists that increase the NT function
- Use of antagonists that decrease the NT function
Genetic manipulation
- Gene KO in test animals
- Overexpress the NT gene
Transmission pathway stimulation
- Electrical stimulation
- Optogenetic -> Insert a light-sensitive channel into animal neurons by a vector, then stimulate them using light
- Chemogenetic -> Insert a drug-sensitive channel into animal neurons by a vector, then stimulate them using the drug

Question 22

Q

What are the 8 key events that occur during chemical transmission at a synapse that can be mediated?

Answer

A

Precursor supply
Synthesis
Storage
Release
Receptor activation
Reuptake
Metabolism
Autoreceptor activation

Question 23

Q

How is a neurotransmitter precursor delivered to the axons at the synapse?

Answer

A

It is either:

Synthesised in the cell body and transported to the terminal via vesicles
Supplied in the diet, entering the blood and then crossing the BBB using transporters, and then getting into the neuron

Question 24

Q

How is neurotransmitter packaged into vesicles at the nerve terminal?

Answer

A

Using specific vesicular transporters.

Question 25

Q

What leads to release of neurotransmitter at a synapse?

Answer

A

The action potential travels down the neuron, depolarising the membrane and causing calcium channels to open.
The influx of calcium causes vesicles to fuse with the membrane and release the NT into the synapse.

Question 26

Q

Compare the effects of NT binding to ionotropic and metabotropic receptors.

Answer

A

Ionotropic receptors produce fast excitatory or inhibitory effects
Metabotropic receptors produce more long-lasting effects

Question 27

Q

What is the function of autoreceptors on the pre-synaptic neurons?

Answer

A

They act to produce negative feedback of release of the neurotransmitter.

Question 28

Q

Does each neurotransmitter only have one type of receptor in the nervous system? What is the consequence of this?

Answer

A

No, they may have different types and subtypes.
This diversity allows for the targeting of specific receptors with drugs.

Question 29

Q

What are the main forms of excitatory and inhibitory neurotransmission in the CNS?

Answer

A

Excitatory:

Glutamate

Inhibitory:

GABA
Glycine

Question 30

Q

Is glutamate excitatory or inhibitory as a neurotransmitter?

Answer

A

Excitatory (it is the main excitatory NT in the CNS)

Question 31

Q

What neurons use glutamate as a neurotransmitter?

Answer

A

Cortico-cortical neurons
Cortico-subcortical neurons

Question 32

Q

Summarise the synthesis, release, reuptake and recycling of glutamate at a synapse.

Answer

A

Synthesis starts with glutamine, which is converted to glutamate by glutaminase
VGLUT1 or 2 or 3 is the transporter that packages the glutamate into vesicles (in exchange for H⁺)
Upon an action potential, the calcium flux causes release of the vesicle contents into the synapse
Na⁺-dependent transporters reuptake the glutamate into the pre-synaptic neuron and other cells (such as glial cells)
In glial cells, glutamine synthase is used to produce glutamine again, which is shuttled back to the pre-synaptic neuron using glutamine transporters (SN1/SN2 and then SATs)

Question 33

Q

What are the different types of glutamate receptor?

[IMPORTANT]

Answer

A

Ionotropic:

AMPA (use Na⁺ currents)
NMDA (use Ca²⁺/Na⁺ currents)
Kainate (use Na⁺ currents)

Metabotropic:

mGluR_1-8(lead to rise in IP₃)

Question 34

Q

What is the effect of stimulating ionotropic glutamate receptors?

Answer

A

They trigger a mixed fast EPSPs:

First, AMPA receptors trigger a fast-onset depolarisation
This depolarisation releases a voltage-dependent Mg²⁺ block on the NMDA, which allows further depolarisation

Question 35

Q

What is the effect of stimulating metabotropic glutamate receptors?

Answer

A

There are 8 different types of mGluR:

Some lead to slow excitatory effects
Some lead to slow inhibitory effects

Therefore, the effect depends on the particular synapse.

Question 36

Q

Describe the structure and binding sites of the NMDA glutamate receptor. How can this be exploited pharmacologically?

[EXTRA?]

Answer

A

Ligand-gated ion channel (Ca²⁺/Na⁺)
Tetrameric protein

Receptor site:

Glutamate -> Inhibited by ketamine

Modulatory sites:

Glycine (+) -> Inhibited by glycine antagonists
Polyamine (+) -> Inhibited by polyamine antagonists
Magnesium (-)
Calcium-blocking drugs can also inhibit the receptor

Question 37

Q

What is the clinical importance of ketamine?

[EXTRA]

Answer

A

It is a blocker of the glutamate NMDA receptor
It has anaesthetic and analgesic properties

Question 38

Q

What are some putative functions of glutamate as a NT in the brain?

[IMPORTANT]

Answer

A

It is the main excitatory NT in the CNS:

Memory -> Mediates LPT (long term potentiation: a persistent increase in synaptic strength following high-frequency stimulation of a chemical synapse)

Question 39

Q

What is long-term potentiation (LTP)?

Answer

A

The persistent strengthening of synapses based on recent patterns of activity.
In other words, it is the way in which high frequency stimulation at synpases in the brain leads to stronger EPSPs being evoked the next time transmission happens.

Question 40

Q

What are some problems associated with glutamate in the CNS?

Answer

A

Excitotoxicity:

Cerebral ischaemia leads to excessive release of glutamate
This leads to excessive NMDA receptor stimulation, which leads to increased calcium influx
This causes cell death

Pathogenesis of epilepsy:

Too much excitation (or too little inhbition) of glutamate neurons can cause epileptic attacks [CHECK]

Question 41

Q

How can the brain be protected from excitotoxicity in an ischaemic episode?

Answer

A

NMDA receptor antagonists reduce the excitotoxic effects of excessive glutamate release during cerebral ischaemia.
They are effective even after the ischaemic episode is over.

Question 42

Q

How can epilepsy be treated, in relation to glutamate?

Answer

A

Lamotrigine -> It’s anticonvulsant action includes decreased glutamate release.

Question 43

Q

Is GABA excitatory or inhibitory as a neurotransmitter?

Answer

A

Inhibitory -> It is the main inhbitory NT in the CNS

Question 44

Q

Is glycine excitatory or inhibitory as a neurotransmitter?

Answer

A

Inhibitory

Question 45

Q

What neurons use GABA as a neurotransmitter?

Answer

A

Local circuit interneurons in the cerebral cortex
Sub-cortical neurons

Question 46

Q

What neurons use glycine as a neurotransmitter?

Answer

A

Interneurons in the spinal cord

Question 47

Q

Summarise the synthesis, release, reuptake and recycling of GABA at a synapse.

Answer

A

Synthesis starts with glutamine, which is converted to glutamate by glutaminase
Glutamate is then converted to GABA by glutamate decarboxylase
VGAT is the transporter that packages the GABA into vesicles (in exchange for H+)
Upon an action potential, the calcium flux causes release of the vesicle contents into the synapse
Na+-dependent transporters reuptake the glutamate into the pre-synaptic neuron and other cells (such as glial cells) -> GAT1 pre-synaptically and GAT3 on glial cells
In glial cells, GABA transaminase is used to produce glutamate again, which is converted to glutamine by glutamine synthase
Glutamine is shuttled back to the pre-synaptic neuron using glutamine transporters (SN1/SN2 and then SATs)

Question 48

Q

What are the different types of GABA receptor?

[IMPORTANT]

Answer

A

GABA_A -> Ionotropic, Cl^- channel
GABA_B -> Metabotropic, G_i-coupled

Question 49

Q

What is the effect of stimulating ionotropic and metabotropic GABA receptors?

[IMPORTANT]

Answer

A

Ionotropic GABA_A receptors evoke fast inhibitory postsynaptic potentials (IPSPs) -> Due to influx of chloride.
After this, there is a slower, longer-lasting hyperpolarisation due to the metabotropic GABA_B receptors -> Due to the opening of potassium channels.
The metabotropic GABA_B receptor also lead to decreased calcium influx (due to closing of calcium channels) and decreased intracellular cAMP

Question 50

Q

Describe the structure and binding sites of the GABA_A receptor. How can this be exploited pharmacologically?

[EXTRA?]

Answer

A

Ligand-gated ion channel (Cl^-)
Pentameric structure with multiple chemical binding sites

Receptor site:

GABA -> Inhibited by GABA antagonists

Modulatory sites:

Benzodiazapine binding site -> Benzodiazapine (+), Benzodiazapine antagonists and inverse agonists (-)
Channel modulators (+) -> Including arbiturates & steroidal anaesthetics
Channel-blocking drugs (-) -> These are convulsant agents (thus they are not used therapeutically)

Question 51

Q

Give an example of a benzodiazapine and what its effect is on the GABA_A receptor.

[IMPORTANT]

Answer

A

Valium is an example
Benzodiazapines have neuromodulatory action
They increase the affinity of the receptor for GABA and increase the probability that GABA will open the channel
Thus, this leads to increased CNS inhibition

Question 52

Q

What are some putative functions of GABA as a NT in the brain?

[IMPORTANT]

Answer

A

It is the major inhbitory NT involved in:

Movement control -> In the basal ganglia
Downregulation of anxiety and epilepsy

Question 53

Q

What are some pathologies associated with GABA in the CNS?

Answer

A

Anxiety -> Reduced GABA signalling
Epilepsy -> Reduced GABA signalling
Huntington’s disease -> Loss of GABA-containing long projection neurones leads to uncontrolled movement.

Question 54

Q

How can anxiety be treated, with relation to GABA?

Answer

A

Benzodiazepine agonists (eg. diazepam) relieve anxiety by facilitating GABA_A receptor function.

Question 55

Q

How can epilepsy be treated, with relation to GABA?

Answer

A

Major classes of anticonvulsants:

Increase GABA transmission by facilitating GABA_A receptor function (eg. benzodiazepines, barbiturates)
Inhibit GABA metabolism (valproate)
Inhibit uptake (tiagabine)

Question 56

Q

What are some examples of drugs that:

Inhibit GABA breakdown
Mimick GABA actions

[IMPORTANT]

Answer

A

Inhibit GABA breakdown -> Valproate [IMPORTANT]
Mimick GABA actions -> Benzodiazepines, Barbiturates (Note that these are not GABA receptor agonists, but neuromodulators that sensitise the receptor to GABA)

Question 57

Q

What neurons use GABA as a neurotransmitter?

Answer

A

Brainstem neurons -> Basal forebrain, septum and striatum
Peripheral neurons

Question 58

Q

Summarise the synthesis, release, reuptake and recycling of ACh at a synapse.

Answer

A

Synthesis starts with choline, which is combined with acetate by a choline acetyl transferase (CAT)
VAChT is the transporter that packages the ACh into vesicles (in exchange for H⁺)
Upon an action potential, the calcium flux causes release of the vesicle contents into the synapse
There is no specific transporter for ACh, so it is broken down on the post-synaptic cell membrane by acetylcholinesterase (AChE)
Na⁺-dependent transporters reuptake the choline into the pre-synaptic neuron

Question 59

Q

What enzymes are used to synthesise and breakdown ACh?

Answer

A

Synthesis -> Choline acetyl transferase (CAT)
Breakdown -> Acetylcholinesterase

Question 60

Q

What are the different types of ACh receptor?

[IMPORTANT]

Answer

A

Muscarinic (metabotropic) -> G_q_/i-coupled
Nicotinic (ionotropic) -> Na⁺channels

Both are found in the CNS and periphery.

Question 61

Q

What are some putative functions of ACh as a NT in the CNS?

[IMPORTANT]

Answer

A

Cholinergic neurons rich in basal forebrain (nucleus basalis), septo-hippocampal pathway, and striatum:

Memory
Movement
Reward and motivation

Question 62

Q

What are some pathologies associated with ACh in the CNS?

Answer

A

Amnesia -> Lesions of cholinergic pathways and muscarinic antagonists lead to memory loss
Alzheimer’s disease -> Loss of cholinergic neurons
Nicotine addiction -> Related to ACh interaction with midbrain dopamine (mesolimbic) pathways.

Question 63

Q

How can Alzheimer’s disease be treated, with relation to ACh?

Answer

A

Cholinesterase inhibitors (tacrine) have some therapeutic benefit.

Question 64

Q

How can Parkinson’s disease be treated, with relation to ACh?

Answer

A

Muscarinic antagonists (benzatropine) are helpful in treating tremor.

Answer 64

A

Dopamine
Noradrenaline
Serotonin (5-HT)

Answer 65

A

Neurons that arise from the midbrain.

Answer 66

A

Tryptophan or tyrosine

Answer 67

A

NOTE: This should be covered more in a later lecture. If not, add flashcards.

Answer 68

A

They are all GPCRs, except 5-HT₃.

NOTE: This should be covered more in a later lecture. If not, add flashcards.

Answer 69

A

More than 50

Answer 70

A

Both in the CNS and periphery.

Answer 71

A

Small molecular weight neurotransmitters (e.g. substance P or 5-HT)

Answer 72

A

Tachykinins
Opioids

Answer 73

A

Class: Tachykinins (peptide neurotransmitters)
Receptors: Slow excitatory responses via G-protein coupled receptors (NK1-3)
Localisation: Primary sensory afferents (pain pathways), medulla (vomiting centre) and limbic system (anxiety pathways).
Function: Involved in emesis, pain processes, and behavioural response to anxiety & stress (via NK1 receptors)

Answer 74

A

NK1 (the receptor for substance P) antagonists have antiemetic, analgesic and anxiolytic & antidepressant properties.

Answer 75

A

Enkephalins
Endorphin
Dynorphin
Endomorphin

Answer 76

A

Receptors: Inhibitory, G-protein coupled. CNS effects mainly mediated by inhibitory µ receptors.
Function:
- Mediation of pain transmission -> Opiate analgesics (eg. morphine) act on µ receptors in the spinal cord to relieve pain (also limbic system & brainstem)
- Reward and motivation -> Morphine euphoria & addiction linked to opioid interaction with midbrain dopamine (mesolimbic) pathways.

Answer 77

A

Synthesis: Nitric oxide synthase found in many CNS neurons
Cellular effects: NO diffuses from neurons to increase cGMP and regulate intracellular Ca²⁺
Function: Possible role in learning & memory -> NO facilitates LTP (long-term potentiation) by diffusing from postsynaptic neuron to facilitate release of glutamate (‘retrograde’ transmission)

Answer 78

A

Excessive NO is neurotoxic.

Answer 79

A

NOS inhibitors

Answer 80

A

They are all found in the brainstem. They make up less than 1% of the neurons in the brain, but they are functionally very important.

Answer 81

A

They are globally distributed throughout the brain
A single monoamine neuron can have multiple targets
Monoamine neurotrasmitters are released at varicosities

Answer 82

A

They are found in the locus coeruleus (a nucleus in the pons of the brainstem)
The supply the forebrain, cerebellum and also go down the spinal cord

Answer 83

A

They are found in the:
- Substania nigra pars compacta (a basal ganglia structure in the midbrain of the brainstem)
- Ventral tegmental area (just next to the substantia nigra in the midbrain of the brainstem)
The supply the forebrain

(Note: There is also a small area near the hypothalamus)

Answer 84

A

They are found in the aphe nuclei (along the midline of the brainstem, as part of the reticular formation?)
The supply the forebrain, cerebellum and also go down via the spinal cord

Answer 85

A

(Matsuda, 2009):

Reconstructed the axon of a single dopamine neuron that sent axons to the striatum
This axon occupied 6% of the volume of the striatum, meaning that it had many targets within the striatum

Answer 86

A

They are mostly released at en passant varicosities, which means that the NTs act on more than one target.

Answer 87

A

Spontaneous, rhythmical firing provides constant tone at neuronal targets.

Answer 88

A

Sleep-wake cycle and maintaining arousal (i.e. a waking state)
Encode specific behavioural events:
- Dopaminergic neurons are involved in learning to associate a stimulus with a reward
- 5-HT neurons are involved in learning to associate a stimulus with a punishment (maybe)
Mood regulation
Anxiety and fear mechanisms
Cognition and attention
Motor function
Prolactin secretion
Nausea and vomiting
Feeding

(Note that not all of these are due to each type of monoamine. There are flashcards later that break this down into noradrenaline, dopamine and 5-HT.)

Answer 89

A

(Moruzzi, 1949)

Inducing a lesion at the medulla-spinal cord level has no effect on wakefulness (as shown by the EEG)
Inducing a lesion in the midbrain causes a sleep-like state (as shown by the EEG)
Therefore, somewhere between these two points must be the neurons responsible for wakefulness, which are the monoamine neurons

(Jacobs, 1976)

Found that raphe nuclei cells fired more during wakefulness than during sleep

Answer 90

A

(Schultz, 1997):

In animals that were not conditioned to associate a stimulus with a reward, the firing of dopamine neurons in the midbrain was shown to increase after the reward (shown by the R line on the diagram)
In animals that were conditioned to associate a stimulus with a reward, the firing of dopamine neurons in the midbrain was shown to increase after the stimulus (shown by the CS line on the diagram) -> If no reward occured, then there was a decrease in firing when the reward should’ve been

Answer 91

A

Starting point for synthesis is tyrosine, which is taken in via the diet, then transported across the BBB by an amino acid transporter
Tyrosine is converted to L-DOPA by tyrosine hydroxylase
L-DOPA is converted to dopamine by DOPA decarboxylase
Dopamine is transported into vesicles by VMAT (vesicular monoamine transporter)
Inside the vesicles, dopamine is converted to noradrenaline by dopamine beta-hydroxylase
Noradrenaline is released upon an action potential, due to depolarisation of the membrane leading to an influx of calcium
It can bind to alpha-1/2 or beta-1/2 receptors on the postsynaptic membrane, and alpha-2 autoreceptors on the presynaptic membrane
Reuptake into the presynatic terminal occurs via NET (norepinephrine transporter) and into the postsynaptic terminal via ENT (extraneuronal uptake)
Noradrenaline can then be reused or broken down
Break down occurs by:
- Mostly via MAO (monoamine oxidase) in the presynaptic terminal
- COMT (catechol-O-methyltransferase) on the postsynaptic membrane (although we don’t fully know the location)

Answer 92

A

α₁
- Excitatory?, G_q-coupled
- Leads to an increase in PLC activity, so that IP₃ and DAG are increased, mobilising Ca²⁺
- [ADD MORE]
α₂
- Inhibitory, G_{<span>i</span>}-coupled
- Leads to a decrease in cAMP
- On pre-synaptic membrane (autoreceptor) AND post-synaptic membrane
β₁ and β₂
- Excitatory, G_s-coupled
- Leads to an increase in cAMP

Answer 93

A

Decrease transmission:

Inhibit synthesis -> e.g. α-methyl-p-tyrosine inhibits tyrosine hydroxylase
Inhibit VMAT -> e.g. Reserpine
Inhibit adrenoceptors -> e.g. Propranolol is a beta antagonist, Prazosin is an α₁ antagonist
Stimulate inhibitory adrenoceptors -> e.g. Clonidine is an α₂ agonist [CHECK]

Increase transmission:

Stimulate exocytosis -> e.g. Ritalin or amphetamine
Inhibit reuptake -> e.g. Reboxetine inhibits NET
Inhibit metabolism -> e.g. Phenelzine inhibits MAO, Tolcapone inhibits COMT

Answer 94

A

Prazosin -> α₁ antagonist
Phenelzine -> MAO inhibitor
Propranolol -> β antagonist

Answer 95

A

α-methyl-p-tyrosine inhibits tyrosine hydroxylase. This is not selective for NA though.

Answer 96

A

Reserpine -> Used to treat hypertension

Answer 97

A

Prazosin -> Used to treat hypertension and PTSD symptoms

Answer 98

A

Clonidine -> Used to treat hypertension, ADHD and drug withdrawal.

Answer 99

A

Ritalin or amphetamine -> Ritalin is used to treat ADHD.

Answer 100

A

Reboxetine inhibits NET -> Used as an antidepressant.

Answer 101

A

Phenelzine inhibits MAO -> Used as an antidepressant
Tolcapone inhibits COMT -> Used to treat Parkinson’s disease

Answer 102

A

Sleep-wake cycle
Arousal
Mood regulation
Anxiety & fear mechanisms
Cognition (such as attention)

Answer 103

A

Starting point for synthesis is tyrosine, which is taken in via the diet, then transported across the BBB by an amino acid transporter
Tyrosine is converted to L-DOPA by tyrosine hydroxylase
L-DOPA is converted to dopamine by DOPA decarboxylase
Dopamine is transported into vesicles by VMAT (vesicular monoamine transporter)
There is no dopamine beta-hydroxylase enzyme, so it is not converted to noradrenaline
Dopamine is released upon an action potential, due to depolarisation of the membrane leading to an influx of calcium
It can bind to D_1-5 receptors on the postsynaptic membrane, and D_2-3 autoreceptors on the presynaptic membrane
Reuptake into the presynatic terminal occurs via the dopamine transporter (homologous to the norepinephrine transporter)
Doapmine can then be reused or broken down
Break down occurs by:
Mostly via MAO (monoamine oxidase) in the presynaptic terminal
COMT (catechol-O-methyltransferase) on the postsynaptic membrane (although we don’t fully know the location)

Answer 104

A

D₁ receptors (D₁, D₅):

G_s-coupled, Stimulate adenylate cyclase to increase cAMP

D₂ receptors (D₂, D₃, D₄)

G_i-coupled, Inhibit adenylate cyclase to decrease cAMP
D₂ and D₃ are also on the pre-synaptic membrane

Answer 105

A

Some neurons express the D₁ family (D₁ and D₅), while others express the D₂ family (D_2-4).

Answer 106

A

Decrease transmission:

Inhibit synthesis -> e.g. α-methyl-p-tyrosine inhibits tyrosine hydroxylase
Inhibit VMAT -> e.g. Reserpine
Inhibit receptors -> e.g. Haloperidol is a D₂ antagonist

Increase transmission:

Stimulate exocytosis -> e.g. Amphetamine
Inhibit reuptake -> e.g. Cocaine inhibits the dopamine transporter
Inhibit metabolism -> e.g. Selegiline inhibits MAO_B, Tolcapone inhibits COMT
Stimulate receptors -> e.g. Ropinerole is a D₂ agonist

Answer 107

A

Haloperidol -> D₂ receptor antagonist

Answer 108

A

Haloperidol is a D₂ antagonist -> Antipsychotic medication [IMPORTANT]
Ropinerole is a D₂ agonist -> Used to treat Parkinson’s disease

Answer 109

A

Selegiline inhibits MAO_B -> Used to treat Parkinson’s and depression

Answer 110

A

Motor function
Reward and motivation
Cognition
Prolactin secretion

Answer 111

A

From substantia nigra to striatum -> Nigrostriatal
- Motor function
From ventral tegmental area to nucleus accumbens -> Mesolimbic
- Reward and motivation
From ventral tegmental area to prefrontal cortex -> Mesocortical
- Cognition
From hypothalamus to median eminence -> Tuberoinfundibular
- Prolactin secretion

Answer 112

A

Starting point for synthesis is tryptophan, which is taken in via the diet, then transported across the BBB by an amino acid transporter
Tryptophan is converted to 5-HTP by tryptophan hydroxylase
5-HTP is converted to 5-HT by 5-HTP decarboxylase
5-HT is transported into vesicles by VMAT (vesicular monoamine transporter)
5-HT is released upon an action potential, due to depolarisation of the membrane leading to an influx of calcium
It can bind to 5HT₁_-7 receptors post-synaptically, and some autoreceptors on the pre-synaptic membrane (CHECK what types)
Reuptake into the presynatic terminal occurs via the serotonin transporter (homologous to the norepinephrine transporter)
5-HT can then be reused or broken down
Break down occurs by:
Mostly via MAO (monoamine oxidase) in the presynaptic terminal

Answer 113

A

5-HT receptors are very complex (there are 14 types) and you probably don’t need to know all of the details:

Some are G_q-coupled -> Such as 5-HT_{2A, 2C}
Some are Gi-coupled -> Such as 5-HT_1A
Some are Gs-coupled -> Such as 5-HT_{4, 6, 7}
5-HT₃ is the only ionotropic receptor, allowing sodium in

There are also presynaptic receptors (autoreceptors).

Answer 114

A

Decrease transmission:

Inhibit synthesis -> e.g. PCPA inhibits tryptophan hydroxylase
Inhibit VMAT -> e.g. Reserpine
Inhibit receptors -> e.g. Risperidone is a 5-HT₂ antagonist, Ondansetron is a 5-HT₃ antagonist,

Increase transmission:

Inhibit reuptake -> e.g. Fluoxetine inhibits the serotonin transporter
Inhibit metabolism -> e.g. Phenelzine is a MAO inhibitor
Stimulate receptors -> e.g. Triptans are agonists at 5-HT₁ receptors, Buspirone is a partial agonist at 5-HT_1A receptors

Answer 115

A

Fluoxetine
Ondansetron
Phenelzine
Buspirone

Answer 116

A

PCPA inhibits tryptophan hydroxylase

Answer 117

A

Risperidone is a 5-HT₂ antagonist -> Used as an antipsychotic
Ondansetron is a 5-HT₃antagonist [IMPORTANT] -> Used to prevent nausea and vomiting
Triptans are agonists at 5-HT₁ receptors -> Used to treat migraines and headaches
Buspirone is a partial agonist at 5-HT_1Areceptors [IMPORTANT] -> Used to treat anxiety

Answer 118

A

Fluoxetine inhibits the serotonin transporter -> Used as an antidepressant

Answer 119

A

Phenelzine is a MAO inhibitor -> Used as an antidepressant

Answer 120

A

(Smith, 1997):

Patients who had recovered from depression and were now stable were given an amino acid mixture, either containing tryptophan or not
In the group containing tryptophan, no return of depressive symptoms was seen
In the group without tryptophan, the depressive symptoms returned after several hours -> This suggested the importance of 5-HT in mood control (since tryptophan is a precursor of 5-HT)