Neuropharmacology: Monoamines: Catecholamines (DA, NE) & 5-HT (Nestler, Hyman, Malenka 2009, Ch 6.1)

Описание: I. Introduction to Widely Projecting Systems
Monoamine neurotransmitters project widely throughout the brain.
These include dopamine, norepinephrine, and serotonin.
Cell bodies sit in the brainstem but axons reach diverse areas.
This organization coordinates responses to global state changes.
Key functions include regulating sleep, arousal, and attention.
They modulate neural activity rather than sending precise data.

II. Dopamine Pathways & Functions
Dopamine is synthesized from the amino acid tyrosine.
The rate-limiting enzyme is tyrosine hydroxylase.
Major cell bodies are in the substantia nigra and VTA.
The nigrostriatal pathway controls motor behavior.
Degeneration of this pathway causes Parkinson disease.
VTA neurons project to the limbic forebrain and cortex.
These projections are critical for motivation and reward.
Dopamine confers motivational salience to rewarding stimuli.
Antipsychotic drugs work by blocking D2 dopamine receptors.

III. Norepinephrine & Arousal Mechanisms
Norepinephrine is synthesized in the locus ceruleus.
This nucleus provides norepinephrine to the cerebral cortex.
It regulates vigilance, attention, and memory consolidation.
Firing rates increase in response to threatening stimuli.
This system interacts with amygdala circuits to process fear.
Norepinephrine acts on alpha and beta-adrenergic receptors.
Beta-blockers can dampen memories formed under strong emotion.
Stress and drugs can up-regulate synthesis enzymes.

IV. Serotonin Synthesis & Regulation
Serotonin is synthesized from dietary tryptophan.
Cell bodies are located in the raphe nuclei of the brainstem.
These neurons innervate virtually every part of the brain.
Functions include mood, emotion, and sensory processing.
Tryptophan depletion can cause a return of depressive symptoms.
There are at least 13 different serotonin receptors.
The 5HT3 receptor is a unique ligand-gated ion channel.
All other serotonin receptors are G protein-coupled.

V. Neurotransmitter Transporters & Clearance
Transporters clear transmitters from the synapse to end signals.
Specific transporters exist for dopamine, norepinephrine, and 5HT.
Reuptake limits the duration of receptor activation.
Monoamine oxidase (MAO) metabolizes these transmitters.
COMT also degrades catecholamines like dopamine.
MAO inhibitors are used to treat depression and anxiety.
Psychostimulants like cocaine block monoamine transporters.

VI. Clinical Pharmacology & Drug Targets
L-Dopa is used to treat Parkinson disease.
It bypasses the rate-limiting step in dopamine synthesis.
SSRIs block the serotonin transporter to treat depression.
Tricyclic antidepressants block norepinephrine reuptake.
Antipsychotics target D2 receptors to reduce symptoms.
Hallucinogens like LSD are partial agonists at 5HT2A receptors.
Stimulants for ADHD interact with dopamine transporters.

VII. Additional Resource Support
See NourishED RFI's NotebookLM Resource Support Page.
https://notebooklm.google.com/noteboo...

VIII. Source
Nestler, E. J., Hyman, S. E., & Malenka, R. C. (2009). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). McGraw-Hill Medical.

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