Exam 1 (chapter 5 catecholamines) | Quizlet

catecholamines are

monoamines (a catechol + an amine group)

catecholamines are synthesized by a multistep pathway in which _____ catalyzes the ______ step

tyrosine hydroxylase

rate-limiting

factors that affect TH activity

1. DA and NE levels in the nerve terminal (negative feedback)

2. cell firing stimulates TH activity through phosphorylation of the enzyme by protein kinases

what catalyzes the conversion of DOPa to dopamine

aromatic amino acid decarboxylase (AADC)

what catalyzes the conversion of dopamine to norepinephrine

dopamine - b - hydroxylase (DBH)

drugs that reduce synthesis inhibit one of the enzymes: ________ blocks _______

a-methyl-para-tyrosine (AMPT) blocks TH

catecholamine storage and release are regulated by

vesicular uptake

autoreceptor activity

cell firing rate

catecholamines are located into synaptic vesicles by

vesicular monoamine transporters (VMAT)

VMAT can be blocked by

reserpine

what is reserpine?

an irreversible inhibitor that causes sedation and depressive symptoms (blocks VMAT)

reversible inhibitors of VMAT are used to

reduce uncontrolled movements in huntington's disease and tardive dyskinesia

VMAT1 is found in the

adrenal medulla

VMAT2 is present in the

brain

both VMAT1 and VMAT2 can be

blocked by reserpine

reversible VMAT2 inhibitors:

tetrabenazine (trade name: Xenazine)

deutetrabenazine (austedo)

valibenazine (ingrezza)

types of catecholamines

dopamine

norepinephrine

epinephrine

adjective forms of the catecholamines

dopaminergic

noradrenergic

adrenergic

the ____ ___ secretes EPI and NE into the bloodstream where they act as ____

adrenal medulla

hormones

amines made by living organisms

biogenic amines

transmitters that have one amine group

monoamines

catecholamines are synthesized from

tyrosine

what is the rate-limiting enzyme

tyrosine-hydroxylase (TH)

catecholamines are synthesized from the precursor amino acid

tyrosine

tyrosine hydroxylase and aromatic amino acid decarboxylase are found in all

catecholaminergic neurons

dopamine - b - hydroxylase is present only in

cells that use norepinephrine as their neurotransmitter

catecholamine synthesis can be increased by administering

precursors such as tyrosine or L-DOPA

precursor used to treat Parkinson's disease

L-DOPA

the membrane of a dopaminergic neuron possesses

autoreceptors

when these are stimulated, they inhibit subsequent DA release by the cell

psychostimulants ____ and _____ cause release of catecholamines without nerve firing

amphetamine

methamphetamine

with amphetamine and methamphetamine in animals, they show increased activity; at high doses

stereotyped behaviors occur

in humans, drugs (psychostimulants) effects include

alertness, high energy levels, euphoria, insomnia

what are those stereotyped behaviors seen in lab animals taking psychostimulants?

intense sniffing, repetitive hand and limb movements, and licking and biting

dopamine release is inhibited by

autoreceptors

apart from autoreceptors, what also influences dopamine release

neuron firing pattern

what are the two forms of neuron firing pattern that influence dopamine release

single-spiking mode and burst mode

action potentials appear at irregular intervals

single-spiking mode

(tonic release)

type of release associated with single-spiking mode

tonic release

trains of 2-20 spikes at higher frequency, transmitter release occurring faster than it can be cleared and/or metabolized

burst mode

(phasic release)

type of release associated with burst mode

phasic release

the autoreceptors inhibit neurotransmitter release through two combined mechanisms

1) inhibiting action of voltage-gated ca2+ channels - reduces DA release by directly reducing amount of activity mediated Ca2+ influx needed for vesicular exocytosis

2) enhancing the opening of a type of voltage-gated K+ channel - indirectly reduces Ca2+ influx by shortening the duration of action potentials

what catecholamine axons form en passant (in passing) synapses

dopamine and norepinephrine

fibers have repeated swellings called _______ along their length, filled with synaptic vesicles

varicosities

what are some details about varicosities and their role as releasing sites for DA?

but only 30% of varicosities have release sites for Dopamine; questions regarding their function remain

after catecholamines are released what happens?

they are recycled by the process of reuptake

how does reuptake work for DA and NE?

DA and NE transporters return the transmitters to the releasing cell for breakdown or repackaging into vesicles

uptake of catecholamines through

by postsynaptic cell or glial cells by non-selective transporters

what do transporter-blocking drugs do?

enhance DA or NE transmission by increasing the amount of the NT available

compounds that block both DA and NE reuptake include

methylphenidate (Ritalin) and amphetamine (Adderall)

what are Ritalin and Adderall typically for?

standard treatments for ADHD

compounds that block NE transporters include

atomoxetine (Strattera) and reboxetine (edronax)

?what is Strattera for

newer adhd medication

what is reboxetine for?

newer generation antidepressant drug

compounds that block combinations of catecholamine and serotonin (5-HT) reuptake:

tricyclic antidepressants, which block the NE and 5-HT transporters, and cocaine, which inhibits reuptake of all three major monoamine transmitters

what are the three monoamine transmitters?

DA, NE, and 5-HT

extracellular DA levels are strongly elevated by

treatment with a DA reuptake inhibitor

catecholamine levels are regulated by

metabolizing enzymes

breakdown of catecholamines involves

monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT)

what metabolizing enzyme was used to treat depression but had dangerous side effects

nonselective MAO inhibitors

types of selective MAO inhibitors

moclobemide (MAO-A) selegiline (eldepryl) rasagiline (azilect) (MAO-B)

selective MAO inhibitors used for depression

moclobemide (MAO-A)

selective MAO inhibitors used for Parkinson's disease

Selegiline (Eldepryl) and rasagiline (Azilect)

what are the two types of MAO

MAO-A and MAO-B

MAO expressed by catecholamine neurons

MAO-A

MAO found in other types of neurons and glial cells (astrocytes)

MAO-B

nonselective mao inhibitors block both

MAO A and MAOB

what nonselective MAo inhibitors are used to treat depression and have dangerous side effects

phenelzine (nardil)

tranylcypromine (parnate)

COMT acts on compounds containing the

catechol structure

action of MAO and COMT produce metabolites:

DA metabolite

NE metabolites

what is the DA metabolite

homovanillic acid (HVA)

what is the NE metabolites?

3-methoxy-4-hydroxy-phenylglycol (MHPG) in the brain and vanillymandelic acid (VMA) in PNS

levels of metabolites in blood, urine, and CSF provide an indication of

catecholaminergic activity

COMT inhibitors that enhance l-DOPA availability in Parkinson's patients

entacapone (comtan)

opiscapone (ongentys)

tolcapone (tasmar)

What type of compound would reduce the availability of NE?

b. Tyrosine hydroxylase inhibitor

two important dopaminergic cells groups are found in the

midbrain

(A9 and A10)

A9 is in the

substantia nigra (midbrain)

axons ascend to the dorsal striatum in the forebrain (the nigrostriatal tract)

A10 is in the

ventral tegmental area (VTA)

pathways of the A10

mesolimbic dopamine pathway

mesocortical dopamine pathway

VTA to limbic system

mesolimbic dopamine pathway

VTA to the cerebral cortex

mesocortical dopamine mathway

a small groups of cells in the hypothalamus gives rise to the

tuberohypophyseal dopamine pathway

important in controlling secretion of prolactin by the pituitary gland

tuberohypophyseal dopamine pathway

there are also DA-containing neurons within

sensory structures such as the olfactory bulbs and the retina

the ascending DA systems can be divided into

3 pathways

nigrostriatal pathway

mesolimbic pathway

mesocortical pathway

the nigrostriatal pathway originates in the _____ and innervates the _______

substantia nigra (a9 cell cluster)

caudate-putamen (dorsal striatum)

the mesolimbic pathway originates in the _____and innervates various ____

VTA (A10 cell cluster)

limbic system structures (nucleus accumbens, hippocampus, lateral septum, amygdala)

the mesocortical pathway originates in the _____ and innervates the

VTA

cerebral cortex

______ dopamine pathways have been implicated in several important behavioral functions

ascending

____ tract facilitates voluntary movement

nigrostriatal

parkinson's disease has been linked with

loss of DA neurons in the substantia nigra

mutations in genes for TH, AADC,

tetrahydrobiopterin (TH cofactor)

(rare inborn errors of metabolism)

experimental lesions of the nigrostriatal tract by

neurotoxins

(6-hydroxydopamine 6-OHDA and 1-methyl-4-phenyl-1,2,3,4,5,6 - tetrayhydropyridine)

mice have been genetically engineered to lack

dopamine dopamine

what is a dopamine-deficient (DD) mouse

gene for TH is knocked out but not the gene for DBH - NE can be synthesized but not DA

DD mice exhibit severe

aphagia, adipsia, and hypoactivity

lack of feeding behavior

aphagia

lack of drinking

adipsia

the behaviors of DD mouse can be restored by

L-DOPA

mouse models confirmed a critical role for the ___ ___ in many of the activational, motivational, and cognitive functions of DA

dorsal striatum

activates arousal and locomotor behavior: different neurons mediate the effects of rewarding and aversive stimuli

mesolimbic dopamine pathway

input to the PFC helps regulate cognitive functions such as attention and working memory

mesocortical pathway