exam 2

three types of main catecholamines

dopamine, norepinepherine, epinepherine

catecholamines are

monoamines

monoamines

a large group of neurotransmitters derived from aromatic amino acids

example of monoamines

phenylanine, tyrosine, tryptophan, and thyroid hormones

catecholamine synthesis

begins with amino acid tyrosine

in catecholamine synthesis TH

is the raqte limiting enzyme in the pathway, it determines the overall rate of DA or NE synthesis

neurons that are positive for TH make__ and are likely___ neurons

dopamine, dopaminergic

Neurons that are positive for DBH make___ and therefore are _

norepinephrine and are likely noradrenergic neurons.

reasoning for neurons.

The reasoning is that TH (tyrosine hydroxylase) is required to make L-DOPA → dopamine, while DBH (dopamine β-hydroxylase) converts dopamine → norepinephrine

neurotransmitter function of epi is relatively

minor

epinepherine is a major

circulationg catecholamine in Hu

adrenal medulla secretes and act as

epi 80% and NE 20%, hormones

TH in the rodent brAIN

regions containing catecholamine processing neurons

activity of TH is regulated by

Neurons firing at a high rate or negative feed back

Neurons firing at a high rate increase activity of TH

promoting the synthesis of catecholamines such as epinephrine and norepinephrine. accelerates. happens during like stress

negative feedback

decrases TH activity, limiting catecholamine synthesis. high levels of catecholamines inhibit further synthesis.

catecholamine synthesis can be increased by

administering a precursor L-DOPA

catecholamine synthesis can be blocked by

A AMPT

post synthesis catecholamines are packed into vesicles by

vesicular monoamine transporter

VMAT can be blocked by the drug

reserpine, which inhibits catecholamine storage. dopamine and norepinepherine are not protected and broken down

resperine backround

arvid carlsson, decreases DA and NE causing sedation and depression loss of movement conrtrol

how is resperine reversed

L-DOPA

resperine led to the

development of the cathecholamine thory of depression and understanding of parkinsons

AMPH increases

DA levels and behavioral activation

at higher dose of AMPH

increased activity is replaced by stereotyped behaviors (intense. sniffing, licking,biting)

catecholamines are normally released by _____ when a nerve impulse reaches the ___

exocytosis,terminal

some drugs cause release independently of

cell firing (non-vesicular release)

catecholamine release is inhibited by

auto receptors

autoreceptors enhance the opening by opening ____ this then shortens the duration of AP ns reduces ___ decreasing vessicle exocytosis

voltage gated k+ channels, ca2+ influx

DA autoreceptor subtype

d2

Ne autoreceptor subtype

a2

drugs that stimulate autoreceptors decrease catecholamine autoreceptor antagonists increase rate of _

release,release

what happens if d2 auto receptor is removed

mice become more active and sensitive to cocaine

clonidine reduces

anxiety, agitation, muscle aches, runny nose

cloninidine a2 agonist

withdrawal from the opiod drugs activates the noradrenergic system= withdrawl symptoms. clonodine is used to treat the symptoms

yohimbine a2 aantagonist

increases NE release, provokes withdrawl symptoms and drug craving in opiod patients

inactivation of catecholamines after release

transporter reuptake by DAT/NET to nerve terminals, repackaging by VMAT Breakdown by MAO/COMT

datnet brings it back vmat stores it and maocomt

destroys it

breakdown of catecholamines

tyrosine, dopa, dopamine, norepinepherine, epinepherine

dopamine with monoamine oxidase turns into

dopac

dopac via COMT

HVA

NE through mao/comt

VMA

Metabolites pass ___ then bloodstream and the eliminated by urine

CSF

levels of metabolite in urine is a indication of

catecholaminergic activity

no DA transporters (DAT knockout) leads to

hyperactivity. no DA reuptake +prolonged extracellular DA= HYPERACTIVITY

No DAT mean less likely to administer

cocaineand other stimulant drugs, as they rely on DA transporters for their effects.

drugs that alter catecholamine uptake

tricylic antidepressants inhibit reup of NE and 5HT, reboxetine and straterra block NE transporters, COCAINE inhibits the reuptake of all monoamine transmiterrs DA,NE,5ht

MAO inhibitors are used to treat

depression

COMT inhibitors

enhance LDOPA treat parkinsons by preventing breakdown of DOPA

dopamine acts as

motivation currency, motor or action modulator,

dopamine is a modulator for action/ motor because

it regulates the initiation and execution of movements, influencing both voluntary actions and automatic responses.

norepinephrine acts a alertness amplifier by

boosting attention and vigilance, fight or flight regulation

brain catecholamines act as the nervous systems

motivation,attention, and motor action network. It helps decide what to focus on and respond

dopaminergic system originates in several cell groups mostly in the

brainstem a9,a10

da neurons make up

1%of neurons in the brain but have effect on behavior

4 major dopaminergic pathways in the brain

nigrostriatal, mesolimbic, mesocortical, tuberoinfundibular pathway

nigrostriatal pathway anatomy

cell bodies in the substantai nigra, extend to the caudate putamen and play a key role in movement control, posture, muscle tone.

parkinsons involves the loss of DA neurons in the substantia nigra and denerves the

striatum

neurotoxins 6-odha and MPTP have been used to damage

nigrostriatal pathway

cell bodies in the ventral tegmental area give rise to two pathways

mesolimbic pathway and misocortical pathway

mesolimbic pathway

from the VTA to various structures in the limbic system, reward pathway compulsive behaviors, addiction

mesocortical pathway

from vta to prefrontal cerebral cortex, abnrmal function in psychoses, associated with negative symptoms in schizophrenia

tuberoinfundibular pathway

hypothalamus sends to da into mediaNA eminence- portal vessels, anterior pituitart\text{, regulates prolactin secretion from the anterior pituitary, influencing lactation and reproductive functions.}

how many dopamine receptor subtypes are there

5, d1to d5

d1 and d5 receptors are

alike

d2,3,4 receptors are a seperate

family (d2 like receptors)

d1 receptor ___ adenylyl cyclase and synthesis of cAMP

stimulates

d2 receptor ____ adenylyl cyclase and synthesis of cAMP

inhibits

dopamine recepto antagonist

supress exploratory and locomotor activity, d2 receptors

forepaw on horizontal bar test

is a behavioral test used to assess motor coordination and balance in rodents by placing them on a horizontal bar. testing lack of spontaneous movement

catalepsy

is a state of waxy flexibility and unresponsiveness, often seen in certain neurological conditions or as a side effect of antipsychotic medications. It can result in a lack of voluntary movement.

d1 receptor knockout mice exhibhot deficits in

several kinds of cognitive tasks

D2 knockout mice show impairment in

spontaneous movement, coordination and posture control

doubl knockout of d1 and d2 lead to

fatality in 2-3 weeks

if a d2 receptor is given to rats on a long term basis rats develop

behavioral supersensitivity

behavioral supersensitivity

increased density of d2 receptors on post synaptic cells in the striatum resulting in heightened responsiveness to dopamine.

haloperiodol

aantagonist of d2 receptors ap

apomorphine

is a dopamine agonist that stimulates both D1 and D2 receptors, often used in the treatment of Parkinson's disease.

quinpiriole

stimulates d2 and d3 receptors agonist

noradrenergic system has

CNS and PNS components

cns noradrenergic system

cell bodies in the brainstem LC that project to various brain regions, including the cortex and limbic system. It plays a key role in arousal, attention, and stress response.

LC is located in the

pons

afrenergic receptor subtypes, both are _ and _

alpha and beta, metabotropic

alpha 2 receptors

Gi inhibit adenylyl cyclase and reduce synthesis of cAMP (autoreceptors) inhibit calcium

alpha 1

Gq calcium, operate phosphoinositoid second messanger system

beta 1 and 2 adrenoceptors

stimulate adenylyl cyclase to enhance synthesis of cAMP and activate protein kinase A.

noradrenergic system behaviors

arousal, cognition, consolidation of memories related to emotional experiences

noradrenergic system arousal

lc neurons fire more rapid awake, lc to medial septal and preoptic areas

alpha 1 and b agonist produce

awakefulness

phenylephrine

mimics adrenaline, alpha 1 receptor agonist, casoconstriction decreases swelling, cause nervousness and restlessness

lc also projects to the

prefrontal cortex (attention, working memory)

alpha 1 adrenergic agonist impairs

spatial working memory

how do a alpha 1 vs alpha 2 receptor affect NEs affect on cognition

moderate NE-a2-improves PFC cognition

high stress NE -a1-impairs PFC cognition

are all a2 receptors autoreceptors

no presynaptic a2 can be autoreceptors, most pfc aitoreceptors are postsynaptoic

NE has a higher affinity for A2 receptors than

a1

administration of a alpha 1 antagonist can restore PFC function and neuron

firing during stress

NE modulates the consolidation of emotional memories in the

nasolateral amygdala

passiveavoidance learning yohibine

proves alpha 2 improved memory consolidation

adrenergic agonists or antagonist are used in treatment of

non psychyatric disorders

anxiety

beta antagonist