1. Outline the Course and Function of the 3 Diffuse Monoaminergic Pathways in the Brain

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:

v  Long axon systems – Corticospinal tract (Glutamate)

v  Short axon intrinsic systems (GABA)

v  Controlling systems – divergent (monoamines)

Neurotransmitters

Ø  NA, ACh (ANS)

Ø  Glu, GABA

Ø  Monoamines (NA, 5-HT, DA)

Noradrenaline

Biosynthesis & Release:

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

•  NA usually inhibitory (β-receptors)

•  Normally has excitatory action (α1/β1 receptors)

Regulation of BP

•  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

•  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) Hallucinatory effects

•  Centrally acting 5HT analogues have been know to be hallucinogenic (LSD)

•  ¯ Firing brainstem 5HT neurons ® ¯ cortical inhibition ® ? ® hallucinations

b) Sleep, wakefulness & mood

•  Raphé nuclei activity ® sleep

•  Raphé nuclei lesions ® sleep abolition

5HT precursors are often the target of insomnia treatment (tryptophan; 5-hydroxytryptophan)

•  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