Cns Amine Transmission

Front 1

Amine systems in the CNS? (4)

Back 1

1)Diffuse and widespread
2)Lack of specilised synaptic contacts
3)Modulate fast excitation or inhibition
4)Act at pre or postsynaptic

Front 2

NA pathways in the CNS? (4)

Back 2

1)Origin in Locus Coeruleus
2)C1 nucleus may use adrenaline
3)Diffuse inervations of forebrain (cerebral cortex, hippocampus)
4)Also descending pathways

Front 3

NA in the CNS?
Brainstem
Ascending
Descending

Back 3

Brainstem -blood pressure control via baroreceptors
Ascending - arousal, mood, cognitive processes, learning, memory, movement, attention
Descending - movemnet and pain

Front 4

Effect of Depleation and overactivity of NA?

Back 4

Depletion - depression
Overactivity -mania

Front 5

NA synthesis?

Back 5

Tyrosine =Tyrosine hydroxylase=> DOPA =DOPA decarboxylase=> Dopamine =dopamine beta-hydroxylase in vesicles=>NA (inhibits tyrosine hydroxylase)

Front 6

NA syntheis
Tyrosine hydroxylase blockade and saturation effects?
What increases synthesis?

Back 6

blockade - NA depleation => depression
Saturation - NA unaltered
Syntheis increased by L-DOPA

Front 7

NA inactivation?

Back 7

Uptake 1- into presynaptic cell, most important
Uptake 2 - into glial cell
Degrative enzymes - Monoamine oxidase (MAO), catechol-O-methyltransferase COMT

Front 8

Dopamine origin in the brain?

Back 8

Midbrain origin - substantia nigra (SN) and Ventral tagmental area (VTA)

Front 9

Most important dopamine pathway in brain?

Back 9

Nigro-striantal (N-S)

Front 10

Ventral tegmental area (VTA) to cortex via which dopamine pathway?

Back 10

mesolimbic/mesocortical pathways

Front 11

Dopamine pathway - Tubero Infundibular systems (TI) ?

Back 11

hypothamus to pituritary

Front 12

Dopamine acts on what receptors?

Back 12

D1-5 receptors, all GPCR

Front 13

Dopamine in the CNS?(4)

Back 13

1)movement - N-S parkinsons
2)atention, emotion, reward - VTA to cortex/limbic sys., schizophrenia, drug abuse
3)endocrine - TI sys. pituritary output
4)Vomiting - brainstem

Front 14

Dopamine synthesis?

Back 14

Tyrosine =>Tyrosine hydroxylase=>DOPA=>Dopamine=> transported into vesicles, no D-beta-OH present

Front 15

Dopamine inactivation?

Back 15

uptake transporter specific for DA
MOA, COMT

Front 16

Parkinson's treatment?

Back 16

Due to N-S degeneration
L-DOPA, MAO Inhibitors and COMT Inhibitors

Front 17

Schizophrenia?

Back 17

over-activity in DA mesolimbic/cortical pathways
Psychotropics block DA receptors, Parkinson's like SE, hormonal imbalance via TI pathway

Front 18

5HT origin in brain?

Back 18

raphe nuclei

Front 19

5HT pathway to forebrain and cerebellum from__?

Back 19

dorsal and median raphe

Front 20

5HT pathway, caudal raphe to__?

Back 20

spinal cord and cerebellum

Front 21

5HT receptors?

Back 21

5HT1-7 GPCR
5HT3 ionotropic

Front 22

5HT in CNS?(4)

Back 22

1)mood - cortical/limbic sys, depression
2)sleep - thalamus, activation-wakefulness/insomnia, decreased activity-sleep/sedation
3)feeding - hypothalamus/limbic sys, icreased-loss of apetite, decreased-feeding/weight gain
4)sensory transmission - gating of spinal transmission (pain), cortical inputs dampen sensory overload

Front 23

5HT sysnthesis?

Back 23

Tryptophan (from diet) =tryptophan hydroxylase=>5-hydroxytryptophan=5HTP decarboxylase=>5HT=>transported into vesicles

Front 24

Inactivation of 5HT?

Back 24

reuptake, specific for 5HT, and MAO
blocked by antidepressants - SSRIs

Front 25

Important point on 5HT sysnthesis?

Back 25

Tryptophan hydroxylase not saturated - tryptophan is rate limiting step, increase 5HTP or tryptophan=>increase 5HT=>antidepressant

Front 26

Vesicular uptake of 5HT blocked by?

Back 26

Reserpine =>5HT depleation-depression

Front 27

ACh pathways to cortex/limbic sys. from__?

Back 27

magnocellular neurons

Front 28

ACh pathways to___?

Back 28

hippocampus, thalamus (from brainstem)

Front 29

ACh in CNS? (5)

Back 29

1)receptors both nicotinic (ionotropic) and muscarinic (GPCR)
2)Arousal, sleep, waking - reticular activationg sys. for brainstem, inceasesed ACh=>increased arousal
3)BAsal forebrain neuclei involved in cognition - degeneration in Alzheimers disease
4)learning and memory - septo-hippocampal pathway, alzheimers
5)motor control - basal ganglia (local inter nuerons), parkinsons and huntingtons

Front 30

ACh sysnthesis?

Back 30

Choline (from diet, active uptake) + acetyl CoA (from mitochondria)=choline acetyltransferase=>ACh =>active transport into vesicles

Front 31

ACh inactivation?

Back 31

acetylcholinesterase in synaptic cleft =>choline + acetic acid
Active uptake of choline

Front 32

Rate limiting step in ACh synthesis?

Back 32

Choline acetyl transferase not saturated, choline increases ACh synthesis
Increases ACh - Alzhiemer's therapy