NEUROPSYCHOPHARMACOLOGY: Unit 2 Review

amino acid tyrosine

catecholamine synthesis begins with this

dopamine, norepinephrine, epinephrine

catecholamines include

monoamines

catecholamines belong to this larger group called

adrenal medulla, hormones

__ secrets epinephrine and norepinephrine into the bloodstream, with them acting as __

increased cat. levels of terminal, neuron firing rate

activity of TH is regulated by

precursors

cat. synthesis can be increased by administering

vesicular monoamine transporter (VMAT)

a transporter on the vesicle membrane that is responsible for catecholamine uptake

adrenal medulla and kidney

VMAT 1 catecholamine uptake transporter is found in

the brain

VMAT 2 catecholamine uptake transporter is found in

reserpine

VMAT can be blocked by this drug

sedation and depression-like

if DA and NE are not protected in a vesicle, they are broken down and this behavior occurs

through admission of DOPA

how can behavior induced by lack of NE and DA be reversed

amphetamine and methamphetamine

these drugs cause cat. release independent of cell firing

increased locomotor activity and stereotyped behavior

dopamine meth + amph symptoms

D2

subtype of dopamine receptor that acts as an autoreceptor

they inhibit VGCC + enhance opening of potassium channels to shorten duration of action potentials

how do autoreceptors stop exogenesis

alpha 2

subtype of norepinephrine receptor that is an auto receptor

drugs that inhibit cat. release, increase auto receptors

drugs that stimulate cat. release, inhibit auto receptors

yohimbine

alpha 2 antagonist that blocks the auto receptors and increases norepinephrine release

reuptake and breakdown

how are catecholamines inactivated

reuptake

movement of DA and NE from the synaptic cleft into the nerve terminal via specific membrane transporter proteins for repackaging or break down

MAO-A

metabolizes NE in humans and rodents and DA in rodents

MAO-B

metabolizes DA in humans

COMT

metabolizes both NE and DA

homovanillic acid (HVA)

DA metabolite

3-methoxy-4-hydroxy-phenylglycol (MHPG)

NE metabolite in the brain

vanillylmandelic acid (VMA)

NE metabolite in the PNS

CSF —> bloodstream —> peed out (urine)

path of metabolites

MAO inhibitors

used to enhance catecholamine levels by inhibiting breakdown enzymes

COMT inhibitors

enhance the effectiveness of L-DOPA in treating Parkinson’s disease

three; brainstem

number of primary ascending dopaminergic system pathways that originate in the __

cells in the substantia nigra extend to the caudate-putamen or striatum

nigrostriatal (mesostriatal) tract

nigrostriatal (mesostriatal) tract neurons

these neurons atrophy in Parkinson’s disease

ventral tegmental area (VTA)

meso-tracts refers to cells in the

goes from the VTA to the prefrontal cerebral cortex and hippocampus

mesocortical dopamine pathway

cognition, attention, working memory, schizophrenia, ADHD

implicated in the mesocortical pathway

goes from the VTA to various structures of the limbic system

mesolimbic dopamine pathway

reward processing, arousal, locomotion, addiction

implicated in the mesolimbic pathway

D1 + D5, D2+D3+D4

these dopamine receptor and similar

D1-like receptors

includes D1 and D5 receptor subtypes

D2-like receptors

includes D2, D3, and D4 receptor subtypes

in dorsal striatum and nucleus accumbens

where DA receptor subtypes are found

postsynaptic, autoreceptors, postsynaptic receptors

D1 are most ( ) while D2 are either ( ) or ( )

adenylyl cyclase and synthesis of cAMP

D1 receptor activation stimulates

regulates potassium channels and/or calcium channels via its G Protein

D2 receptor activation inhibits adenylyl cyclase but

Gq-coupled proteins activate PLC

these initiate calcium-signaling

higher affinity

DA has ( ) ( ) for D2 receptors over D1 receptors

phasic

DA firing that engages D1 receptors

tonic

DA firing that engages postsynaptic D2 receptors

striatum (caudate/putamen), globus pallidus (GPe/GPi), subthalamic nucleus, substantia nigra

direct and indirect pathways of movement in the basal ganglia

noradrenergic system central components

cell bodies in the brainstem (pons and medulla) send projections to the forebrain

arousal, cognition, and consolidation of emotional memories

noradrenergic central implicated in

noradrenergic system peripheral components

fight or flight response/sympathetic response

pons and medulla of the brainstem

where NE neurons in the brain are

locus coeruleus

located in the pons; a dense collection of NE neurons

forebrain, cerebellum, and spinal cord

where NE neurons end

adrenal glands

where NE is secreted as a hormone and it plays a key role in the fight-or-flight response

metabotropic, alpha, beta

adrenergic receptors are ( ) and have two subtypes: ( ), ( )

Gq, PLC3, IP3, DAG

alpha 1 receptors use ( ) proteins and operate via ( ), ( ), ( )

G /o, cAMP

alpha 2 receptors use ( ) proteins and reduce synthesis of ( )

Gs, adenylyl cyclase, cAMP

beta 1 and beta 1 adrenoreceptors use ( ) proteins and stimulate ( ) ( ), thus enhancing synthesis of ( )

prefrontal cortex

the locus coeruleus projects to ( ) ( )

working memory

activation of alpha 2 receptors in the PFC enhances ( ) ( )

alpha 1

NE has a lower affinity for ( ) receptors; increase NE associated with stress increase this activation

deleterious

activation of alpha 1 receptors in the PFC has a ( ) effect on cognitive functions

tryptophan

serotonin is synthesized from the amino acid ( )

tryptophan hydroxylase

() () converts tryptophan to 5-HTP

expressed by serotonergic neurons

TPH2 is a form of the tryptophan hydroxylaseTPH gene that is ( )

expressed by 1. 5-HT-secreting cells in the gut and 2. melatonin-secreting cells in the pineal gland

TPH1 is a form of the tryptophan hydroxylase gene that is

tryptophan hydroxylase

the rate-limiting step in serotonin

serotonergic neurons

tryptophan hydroxylase is found only in ( ) ( )

AADC

is found in the synthesis of catecholamines and 5-HT

high carb / low protein

this type of diet can increase 5HT synthesis

stimulates insulin release leading to uptake of amino acids in depot sites which reduces competition for tryptophan to enter the brain

how does a high carb/low protein diet increase 5HT synthesis

serotonin synthesis

condition that results in serious negative symptoms that are often a result of increased 5HT signaling in the body

VMAT2

serotonin is transported into vesicles by ( )

reserpine

depletes 5-HT, which is broken down when not protected in vesicles

5-HT1B, 5-HT1D

terminal autoreceptors such as ( ) and ( ) directly inhibit 5-HT

somatodendritic autoreceptors

indirectly inhibit release by slowing the rate of neuron firing

5-HT transport, SERT

after release, 5-HT is rapidly removed from the synaptic cleft via reuptake by the ( ) also known as ( )

selective serotonin reuptake inhibitors

SERTs are blocked by ( ) ( ) ( ) ( )

cocaine, MDMA

( ) and ( ) can nonselectively block SERT

MAO-A, 5-hydroxyindoleacetic acid

breakdown of 5-HT is catalyzed only by ( ) to yield ( )

activity, serotonergic neurons

levels of 5-HIAA in the brain or CSF are used as a measure of the ( ) of ( ) ( )

midline of the brainstem, dorsal, medial raphe nuclei

most 5HT neurons in the CNS are found along the ( ) ( ) ( ) ( ), particularly the ( ) and ( ) ( ) ( )

forebrain

almost all ( ) regions receive 5HT projections

14, metabotropic

there are ( ) receptors for 5-HT, and most are

hippocampus, septal area, amygdala, dorsal raphe nucleus

5-HT1A receptors are concentrated in the ( ), ( ) ( ), ( ), and ( ) ( ) ( )

autoreceptor, heteroreceptor

5HT1A receptors function as a ( ) or ( )

hyperpolarization

5-HT1A increase the opening of potassium channels and membrane ( )

cAMP, adenylyl cyclase

5-HT1A receptors use the G i/o protein to reduce ( ) synthesis by inhibiting ( ) ( )

mood, cognition, memory

5-HT1A receptors are implicated in the control of ( ), ( ), and ( )

WAY 100635

( ) is a 5-HT1A receptor antagonist

cortex

5-HT2A receptors have large numbers in the ( )

Gq, phosphoinositide

5-HT2A receptors activate the ( ) protein, which then activate the ( ) second-messenger system

calcium, postsynaptic, PKC

5-HT2A receptors increase ( ) levels in ( ) cells and also activate ( )

DOI

5-HT2A agonist which results in characteristic head twitch

hallucinogenic

DOI and related drugs are ( )

5HT1B/1D

triptans are ( ) agonists that cause constriction of the vessels in the brain that ease headache pain

heteroreceptors

many of the 5-HT1B/1D are ( )