Catecholamines

Catecholamines are synthesized from ________

Tyrosine

How is Tyrosine obtained?

Diet protein

Tyrosine —> ______ via _____ —> Dopamine via ______ —> Norepinephrine via _____

DOPA, TH, AADC, DBH

Which step is rate limiting in catecholamine synthesis?

TH

Products of a synthesis pathway inhibit synthesis (negative feedback loop)

End-product inhibition

What happens if you add more TH, AADC, or DBH?

More dopamine or norepinephrine

If Parkinson’s Disease is a result of not enough dopamine, how can we treat it?

Precursor loading with DOPA

Why is it better to give a patient with Parkinson’s Disease DOPA instead of straight Dopamine?

Unlike dopamine, DOPA can pass through the BBB

What happens when L-DOPA is taken alone?

Most of it is converted to dopamine outside of the brain in the PNS by AADC which cannot cross the BBB causing negative side effects

Carbidopa is a ______ inhibitor, preventing the premature conversion of DOPA into dopamine in the PNS allowing more DOPA to reach the brain

AADC

Why is Carbidopa only effective in the PNS and not the CNS?

Cannot cross the BBB

What is the role of VMAT in catecholamine NTs?

Packaging of NTs into vesicles

What happens if you block VMAT?

Decrease in dopamine and norepinephrine

Irreversible VMAT inhibitors result in _____ in animals and _______ in humans.

sedation, depression

Reserpine (VMAT inhibitor) reversal with administration of ______ results in ______

DOPA, happiness

Reversible VMAT inhibitors allows for ________ blocking of dopamine vesicle storage, decreasing dopamine for people with excessive ___________ disorders (i.e. Huntington’s Disease, Tourettes, and Tardive Dyskinesia)

temporary, movement

What are the 2 ways dopamine or norepinephrine increase in release rate?

1. Action potentials

2. Amphetamines without action potentials

Dopamine and norepinephrine release can be decreased by inhibiting ____________

Ca+ channels

Dopamine and norepinephrine release can be decreased by opening _________

K+ channels

What do MAOs do to catecholamines?

Metabolize them

What do MAO-I (MAO Inhibitors) do to catecholamines?

Increase catecholamines

What are MAOIs used to treat if they increase catecholamine (dopamine)?

Depression

Where are a majority of dopaminergic neurons found?

Substantia nigra and VTA

What is dopamine’s involvement in alcohol addiction?

Increase alcohol = increase dopamine = reinforcement = increase dopamine signaling and release (disinhibition hypothesis)

Drugs that impact the VTA (increasing ______) may influence reinforcement, making it more likely to take that drug again, affect activational, motivational, and other cognitive functions.

dopamine

Norepinephrine is synthesized from _________

Dopamine

What is a indicator of a noradrenergic neuron when stained?

DBH

Where are a majority of noradrenergic neurons located?

Locus Coeruleus

Norepinephrine mediates the communication between neurons leaving the __________ and the noradrenergic neurons during flight or flight

spinal cord

Which behavioral response system is norepinephrine involved in?

Fight or flight

Norepinephrine mediates which nervous system?

PNS

Norepinephrine receptors are ___________

metabotropic

What happens when you inhibit norepinephrine autoreceptors?

Increase norepinephrine = Increase PNS activity = Increase anxiety

What happens when you activate norepinephrine autoreceptors?

Decrease norepinephrine = Decrease PNS activity = Decrease anxiety

What are norepinephrine autoreceptor activators used to treat?

Withdrawal symptoms

Norepinephrine is used as a NT in the _____________ cells to target organs

post-ganglionic

Norepinephrine is released by adrenals as a _______ to affect organs

hormone

Agonist of A1 norepinephrine receptors will increase ___________ in certain parts of the Locus Coeruleus

wakefulness

Locus Coeruleus containing the prefrontal cortex means agonism of norepinephrine receptors results in increased ________

cognition

___________- receptors bind norepinephrine and each has a different effect based on its location and metabotropic effects.

Adrenergic