Neurotransmitters 2

Question 1

What is GABA? How is it synthesised? How does it act?

Answer 1

gamma-aminobutyric acid (GABA)
- is a inhibitory neurotransmitter that acts mostly via inhibitory interneurones

GABA is synthesised from glutamate via glutamic acid decarboxylase (GAD)

• GABA enters vesicles and gets released into synaptic cleft
• acts on GABA receptors on the neighbouring neurone and inhibits them

Question 2

How is GABA regulated? Why must it be regulated?

Answer 2

deactivation

• reuptake into the GABAergic neurone by GABA transporters in the synaptic terminal
• breakdown by GABA transaminase

too much GABA
- excessive inhibition
too little GABA
- hyperexcitability

Question 3

What type of receptor is GABAa? What is its effect? What other substances can bind to it? What is their effect?

Answer 3

GABAa
- ionotropic receptor (ligand gated ion channel)
= activation causes the opening of chloride channels. the influx of chloride results in hyperpolarisation and inhibition of neighbouring neurone

benzodiazepines and barbiturates (channel modulators) can bind
- facilitate the opening of the channels
= increased frequency of opening

Question 4

What type of receptor is GABAb? What is its effect? What other substances can bind to it? What is their effect? What drugs can act on it?

Answer 4

GABAb (dimer)

• metabotropic receptor (GPCR)
• inhibits calcium entry, adenylyl cyclase activation, neurotransmitter release
• opens potassium channels causing hyperpolarisation

baclofen can act on it

• inhibits glutamate release
• has an antispastic effect (suppresses muscle spasms)
• treats addiction = alcoholism

Question 5

What is noradrenaline? Where is it found and where does it project to? What is its functions?

Answer 5

is a monoamine
adrenergic neurones reside in the locus coerulus and project to the:
- cortex, amygdala (emotionality), hippocampus (memory), hypothalamus, cerebellum

functions:

• stimulates arousal
• increases heart rate
• associated with drug addiction and gambling (risk taking)
• low levels cause depression
• antihypertensive

Question 6

What are noradrenaline’s receptors?

Answer 6

are all metabotropic receptors (GPCR)
- alpha (A1 and A2) and beta (B1, B2 and B3) adrenergic receptors

presynaptic

• are inhibitory autoreceptors = alpha-2 adrenergic receptors
• carry out negative feedback mechanisms/regulatory systems

post synaptic
- carries the message/signal

Question 7

How can noradrenaline concentrations be regulated?

Answer 7

decrease NA

• reserpine = depletes NA stores by inhibiting NA vesicular uptake
• monoamine oxidase B (MAOb) = metabolises NA

increase (treats depression)

• amphetamine = enters vesicles by displacing NA into the cytoplasm causing increased NA leakage out of the neurone
• cocaine = blocks NA reuptake

Question 8

What are the pathways for DA transmission in the brain?

Answer 8

nigrostriatal

• substanstia nigra to the striatum (basal ganglia)
• for movement regulation (voluntary/purposeful)

mesolimbic

• ventral tegmental area to the nucleus accumbens and amygdala
• for pleasure and reward

mesocorticol

• ventral tegmental area to the cortex (prefrontal cortex)
• for cognition, working memory and decision making

tubero-hypophyseal

• directly into the hypothalamus which is connected to the pituitary gland by the hypothalamic pituitary axis (capillary system)
• for inhibition of milk production by inhibition of prolactin release from the pituitary gland, metabolism, immune system

Question 9

How is dopamine synthesised?

Answer 9

tyrosine is the initial precursor 
- tyrosine hydroxylase acts on it 
DOPA
- DOPA decarboxylase acts on it
dopamine
- dopamine beta-hydroxylase acts on it
noradrenaline 
- phenylethanolamine N-methyltransferase acts on it 
adrenaline

Question 10

What are the classes of DA receptors? What does DA function and dysfunction result in?

Answer 10

D1 receptors - D1 (striatum, hypothalamus) and D5
D2 receptors - D2 (striatum, limbic, thalamus), D3 (limbic) and D4 (cortex and limbic)

function:
- movement, hormone release (prolactin), vomiting
dysfunction:
- addiction, schizophrenia, stereotypy

Question 11

What is serotonin? Where is it found and released? What is it involved in/function?

Answer 11

serotonin
- excitatory neurotransmitter

cell bodies are found in the raphe nuclei and project to:

• cortex (heightened perception)
• hypothalamus (reduced appetite)
• amygdala (elevated mood)
• cerebellum, hippocampus, spinal cord

function:
- mood (anxiety/depression), sleep/wake, psychosis, vomiting, appetite, pain/migraine

Question 12

How is serotonin synthesised?

Answer 12

tryptophan 
- tryptophan hydroxylase acts on it 
5-hydroxytryptophan
- DOPA decarboxylase (L-aromatic acid decarboxylase) acts on it
5-hydroxytryptamine (serotonin)

Question 13

How is serotonin regulated? Why is it important to regulate serotonin concentration?

Answer 13

reuptake by 5-HT transporters
metabolism by monoamine oxidase
inhibition by autoreceptor 5-HT 1D

too much:
- heightened perception, stimulation, reduced appetite, elevated mood

too little:
- depression, pain

Question 14

What are the serotonin receptors?

Answer 14

are all metabotropic except 5-HT3

5-HT1 inhibitory, location: limbic system – mood, migraine
5-HT2 (5-HT2a), excitatory, location: limbic system & cortex
5-HT3 excitatory, location: medulla – vomiting
5-HT4 presynaptic facilitation (ACh) – cognitive enhancement
5-HT6 and 5-HT7 – novel targets, cognition, sleep