Amine Neurotransmitters

Question 1

Amine Neurotransmitters

Answer 1

Noradrenaline
Dopamine
5-hydroxytryptamine
Acetylcholine

Question 2

Key roles of amine neurotransmitters

Answer 2

Roles in arousal, attention, sleep and survival

Question 3

Speed of amine system modulation

Answer 3

Can modulate fast excitation or inhibition.
Via multiple receptors

Question 4

Location of amine systems

Answer 4

Cell bodies restricted to a small number of brainstem nuclei
Gathered together in clusters, based on which NT they produce
Axons project widely and diffusely throughout the nervous system

Question 5

Unlike glutamate and GABA, amine NTs lack…

Answer 5

Specialised synaptic contacts

Question 6

Noradrenaline pathways in the CNS

Answer 6

Origin in the brainstem (locus coeruleus)
Diffuse innervation of forebrain, particularly the cerebral cortex
Also descending pathways

Question 7

Where does noradrenaline bind

Answer 7

α1, α2, β1 and β receptors – GPCRs
Not at ligand gated ion channels

Question 8

Noradrenaline in the brainstem

Answer 8

Blood pressure control
Baroreceptor reflex

Question 9

Noradrenaline in descending pathways

Answer 9

Movement and pain

Question 10

Noradrenaline in Ascending pathways

Answer 10

Arousal and mood
Cognitive processes, learning and memory, movement, attention

Question 11

Noradrenaline synthesis

Answer 11

Tyrosine to L-DOPA by tyrosine hydroxylase
Decarboxylated to dopamine by dopamine dopadecarboxylase.
Taken into vesicles by vesicular monoamine transporter
Dopamine-b-hydroxylase converts it

Question 12

Modulation of Noradrenaline synthesis

Answer 12

Hydroxylation of tyrosine to L-DOPA is rate limiting.
TH and DβOH synthesis can in increased on demand

Question 13

Noradrenaline inactivation

Answer 13

Reuptake by NA transporters into presynaptic terminals
Degradation here by monoamine oxidase (MAO) and catechol-o-methyltransferase (COMT)

Question 14

Modulation of Noradrenaline inactivation

Answer 14

Uptake 1 is the most important transporter and can be blocked
Cocaine blocks uptake
Amphetamine makes reuptake transporters release NA

Question 15

Dopamine pathways in the CNS have … origin

Answer 15

Midbrain

Question 16

Dopamine pathways

Answer 16

Nigro-striatal
Mesolimbic/mesocortical
Tuber-infidibular

Question 17

Mesolimbic/mesocortical pathways

Answer 17

VTA to cortex to hippocampus
(Ventral Tegmental Area)

Question 18

Tuber-infidibular system

Answer 18

From hypothalamus to pituitary

Question 19

Where does Dopamine act in the CNS

Answer 19

At D1-5 receptors
All GCPRs

Question 20

Effects of dopamine

Answer 20

Control of movement (nigro-striatal)
Control of attention, emotion and reward
Control of endocrine function
Brainstem - vomiting

Question 21

Synthesis of dopamine

Answer 21

Tyrosine to L-DOPA by tyrosine hydroxylase
Decarboxylated to dopamine by dopamine dopadecarboxylase.
Taken into vesicles by vesicular monoamine transporter

Question 22

Inactivation of dopamine

Answer 22

Reuptake by DA transporters into presynaptic terminals
Degradation here by monoamine oxidase (MAO) and catechol-o-methyltransferase (COMT)

Question 23

Schizophrenia is caused by …

Answer 23

An overactivity on DA mesolimbic/cortical pathways

Question 24

5HT pathways

Answer 24

Arise from raphe nuclei
Forebrain and from dorsal and median raphe
Caudal raphe to cerebellum
Pontine neurones to spinal cord

Question 25

5HT receptors

Answer 25

5HT 1-7

Question 26

Areas of 5HT action

Answer 26

Cortical/limbic system
Thalamus
Hypothalamus/limbic system
Gating of spinal transmission

Question 27

5HT in the cortical/limbic system

Answer 27

Control of mood
Dysfunction in depression

Question 28

5HT in the thalamus

Answer 28

Control of sleep
Activation = wakefulness/insomnia
Decreased activity = sleep and sedation

Question 29

5HT in the hypothalamus/limbic system

Answer 29

Control of feeding
Increase = loss of appetite
Decrease = feeding/weight gain

Question 30

5HT in spinal transmission

Answer 30

Control of sensory transmission
Gating of spinal transmission (pain)
Cortical inputs dampen sensory overload

Question 31

5HT synthesis

Answer 31

Tryptophan is taken up and hydroxylated
Decarboxylation by AADC
Concentration into vesicles

Question 32

Modulation of 5HT synthesis

Answer 32

Tryptophan hydroxylase is not saturated, therefore consuming more tryptophan can cause greater production.
Vesicular uptake can be blocked by reserpine

Question 33

Reuptake of 5HT

Answer 33

Inactivation and reuptake by MAO
Uptake is specific for 5HT and can be blocked by SSRIs

Question 34

Acetylcholine pathways in the CNS

Answer 34

Projection to cortex/limbic system from magnocellular neurons
Projection to hippocampus
Projections from brainstem to thalamus and other sites
Local interneurons in basal ganglia

Question 35

Receptors for Ach

Answer 35

Both nicotinic (ionotropic) and muscarinic (GPCR)

Question 36

Ach in the brainstem

Answer 36

Reticular activating system
Arousal, sleep and waking
Increased Ach = arousal

Question 37

Ach in the basal forebrain nuclei

Answer 37

Cognition

Question 38

Ach in the septo-hippocampal pathway

Answer 38

Learning and memory

Question 39

Ach synthesis

Answer 39

Same as NMJ
Choline is taken up (active uptake)
Acetyl CoA is added by ChAT
Active transport into vesicles

Question 40

Modulation of Ach synthesis

Answer 40

ChAT is not saturated, so dietary choline is rate limiting

Question 41

Inactivation of Ach

Answer 41

Inactivation by acetylcholinesterase in the synaptic cleft, into free choline + acetic acid.
Active uptake of choline