Download Neuroscience 4 – Neurochemistry

Neuroscience 4 – Neurochemistry
Anil Chopra
1. Outline the course and function of the 3 diffuse monoaminergic pathways in the
brain.
2. List the main 5-HT and dopamine receptors and give examples of drugs that
modify their action.
There are 3 main types of Neurotransmitter system:
 Long axon systems – Corticospinal tract (Glutamate)
 Short axon intrinsic systems (GABA)
 Controlling systems – divergent (monoamines)
Neurotransmitters
 NA, ACh (ANS)
 Glu, GABA
 Monoamines (NA, 5-HT, DA)
Noradrenaline
Biosynthesis & Release:
Tyrosine
Tyrosine
hydroxylase
DOPA
DOPA decarboxylase
Tyrosine
Dopamine
Dopamine
Dopamine 
hydroxylase
Noradrenaline
Metabolites
Monoamine
oxidase A
(MAO-A)
Noradrenaline
Action potential
Uptake 1
Noradrenaline
Ca++
Uptake 2
Noradrenaline
Adrenoceptor
Noradrenaline Pathways
Cell body clusters: pons & medulla
i) Locus coeruleus (LC)
ii) Reticular formation (RF)
These are nuclei where noradrenalin is
synthesised.
Functional aspects of Noradrenaline
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NA usually inhibitory (β-receptors)
Normally has excitatory action (α1/β1 receptors)
Regulation of BP
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Central and peripheral NA systems
Clonidine reduces the production of noradrenalin by binding to α2 receptors.
(baroreceptor reflex pathway) This therefore makes clonidine useful as an
anti-hypertensive drug.
[Ca2+ antagonists, ACE inhibitors etc]
Arousal & mood
LC (locus coeruleus) activity is associated with behavioural arousal and mood.
NA deficiency  depression
NA excess
 mania
Amphetamines increase wakefulness + alertness
LC neurons are the site of NA release and increase NA release in times of stress.
Many antidepressant drugs target the neurones to increase NA-ergic transmission e.g.
MAOIs (monoamine oxidase inhibitors) and TCAs (tri-cyclic antidepressants).
5-HYDROXYTRYPTAMINE (5HT)
NB – also known as serotonin.
5HT Pathways
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Distn widespread; similar to NA
Cell body clusters: pons & upper medulla
It is released from the raphe nuclei.
Rostral  ascending pathways (MFB)
Caudal  descending pathways
Functional aspects of 5 –Hydroxytryptamine
a)
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b)
Hallucinatory effects
Centrally acting 5HT analogues have been know to be hallucinogenic (LSD)
 Firing brainstem 5HT neurons   cortical inhibition  ?  hallucinations
Sleep, wakefulness & mood
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Raphé nuclei activity  sleep
Raphé nuclei lesions  sleep abolition
5HT precursors are often the target of insomnia treatment (tryptophan; 5hydroxytryptophan)
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MA theory of depression: 5HT
Currently used antidepressant drugs:
inhibit 5HT breakdown: MAOIs
inhibit 5HT re-uptake TCAs (tricyclic antidepressants); SSRI’s (selective
serotonin reuptake inhibitor)
Subtype-selective 5HT receptor agonists
Dopamine Pathways