Exam 1 (chpt 6 Serotonin) | Quizlet

serotonin synthesis is regulated by

enzymatic activity and precursor availability

what is the neurotransmitter used by serotonergic neurons

Serotonin (5-hydroxytryptamine or 5-HT)

Serotonin is synthesized from tryptophan in two steps

1. catalyzed by tryptophan hydroxylase (TPH), product; 5-hydroxy-tryptophan (5-HTP) (rate-limiting step)

2. catalyzed by aromatic amino acid decarboxylase (AADC) to form 5-HT

synthesized from the amino acid tryptophan in two steps: catalyzed by the enzymes tryptophan hydroxylase and aromatic amino acid decarboxylase

serotonin (5-HT)

two forms of TPH

TPH1 and TPH2

TPH found only in serotonergic neurons

TPH2

TPH found in nonneuronal cells in the gut and pineal gland

TPH1

neuroendocrine tumors in the gut secrete 5-HT; elevated blood levels cause

carcinoid syndrome

carcinoid syndrome can be treated with ______ a nonselective TPH inhibitor; does not cross BBB, only blocks peripherally expressed TPH1

telotristat

TPH1 enterochromaffin cells located in the ______ and melatonin-secreting cells in the ____

gut

pineal gland

serotonin synthesis can be stimulated by

tryptophan or 5-HTP

you can get tryptophan from your

diet

the ratio of tryptophan to other amino acid competitors for transport ccross BBB determines what?

whether serotonin synthesis is stimulated or not

what simulates the uptake of amino acids, except for tryptophan

insulin

a low protein, high carbohydrate meal will do what?

increase ratio of tryptophan to competing large neutral amino acids (LNAA)

transporting and synthesis of serotonin is regulated by the

relative availability of tryptophan vs large neutral amino acids that compete with it for transport across the BBB

what are the two things that can happen as a result of depleting 5-HT and its role in behavior

para-chlorophenylalanine (PCPA)

acute tryptophan depletion (ATD)

selectively blocks 5-HT synthesis by irreversibly inhibiting TPH

para-cholorophenylalanine (PCPA)

large doses of amino acids minus tryptophan

acute tryptophan depletion (ATD)

evelating tryptophan availability has been shown to

enhance cognitive functions such as memory or attention, elevate mood, and improve sleep

administration of pure tryptophan

tryptophan loading

what diet should you take for increase in tryptophan

- supplemented with a-lactalbumin or other high-tryptophan proteins

- consumption of diet rich in carbohydrates but low in protein

reducing brain 5-HT using the AD method seems to do what?

impair memory consolidation of verbal information but has little or no influence on working memory or attention

ATD may also induce a

negative cognitive bias, and reduced sleep duration and quality

individuals display increased sensitivity to threat - or punishment - related stimuli

negative cognitive bias

the effects of ATD may be mediated by reducing

serotonergic activity in an anxiety/fear related circuit that includes the amygdala and medial frontal cortex

95% of ingested tryptophan is metabolized to

kynurenine rather than 5-HT

kynurenine is further metabolized in the

kynurenine pathway; stress and inflammation can stimulate enzymes involved

_____ ___ have been implicated in several psychiatric disorders and neurodegenerative diseases

kynurenine

how do the processes of serotonin and catecholamines compare?

similar processes regulate storage, release, and inactivation of serotonin and the catecholamines

5-HT is transported into synaptic vesicles buy

vesicular monoamine transporter 2 (VMAT2)

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

reserpine (VMAT blocker)

what directly inhibits 5-HT release

terminal autoreceptors

what inhibits the release of 5-HT by slowing the rate of nerve firing

somato-dendritic autoreceptors

release of 5-HT can be stimulated by drugs that are based on the structure of

amphetamine (para-chloroamphetamine, fenfluramine, and MDMA (ecstasy))

in the 1970s, ____ was proposed as a potential adjunct to psychotherapy, but it quickly became a recreational drug

MDMA

what are the effects of MDMA?

heightened arousal, euphoria, enhanced perceptual awareness, and prosocial effects (an ectactogen)

what are the potential toxic effects of MDMDA?

serotonin syndrome (can be life-threatening)

high MDMA dose results in

5-HT depletion in experimental animals; heavy ecstasy use causes serotonergic deficits - determined by neuroimaging

low controlled doses of MDMA have recently been shown to be beneficial as

adjunct to psychotherapy in chronic PTSD

compounds that promote empathy and closeness to others in the absence of hallucinogenic effects

entactogens

inactivation of 5-HT happens by

reuptake by 5-HT transporter (SERT)

antidepressant drugs such as fluoxetine (Prozac) are

selective serotonin reuptake inhibitors (SSRIs)

SERT knockout mice show a variety of

behavioral and physiological abnormalities

5-HT breakdown is catalyzed by

MAO-A to the metabolite 5-hydroxyindoleacetic acid (5-HIAA)

ork?how does Prozac w

By blocking the 5-HT transporter

the serotonergic system originates in the

brainstem and projects to all forebrain areas

serotonergic neurons in the CNS are found along the

midline of the brainstem (medulla, pons, and midbrain), loosely associated with the raphe nuclei

what gives rise to most of the serotonergic fibers in the forebrain

dorsal raphe nucleus (DRN) and median raphe nucleus (MRN)

in the cortex, nerve fibers are _____ at the surface, which has a high

dense

density of dendrites and synaptic connections

the B7 cell group corresponds to the

dorsal raphe

the B8 cell group corresponds to the

median raphe

the firing of dorsal raphe serotonergic neurons varies with

behavioral states

the variability of the firing of dorsal raphe serotonergic neurons is first demonstrated in cats, when a awake each nerve cell does what?

fires at a regular rate (toning firing) , become irregular with slow wave sleep, and stop firing during REM sleep

research with DRN and MRN knockout mice show what about the serotonergic firing?

slow, tonic firing of DRN neurons promotes sleep (Non-rem sleep) burst firing of the same cells favors a state of wakefulness

there is a large family of serotonin receptors, most of which are

metabotropic

how many serotonin receptor subtypes?

14, 5-HT1a and 5-HT2a are most well known

receptors concentrated in the hippocampus, septal area, amygdala and DRN

5-HT1a

receptors that inhibit adenylyl cyclase do decrease cAMP synthesis, increase opening of K+ channels and membrane hyperpolarization

5-HT1a

____ receptor agonists include buspirone, ipsapirone, and 8-hydroxy-1 (di-n-propylamino) tetralin (8-OHDPAT)

5-HT1a

_________ is a 5-HT1a receptor antagonist

WAY 100635

5-HT1a receptors inhibit ____ production and activate ____ channel opening

cAMP

K+

5-HT2a receptors increase intracellular ____ levels and stimulate protein ____ via the phosphoinositide second messenger system

Ca2+

kinase C

5-HT2a receptors occur in the

cortex and other brain areas

function via the phosphoinositide second messenger system; increase Ca2+ levels in the postsynaptic cell' also activate protein kinase C (PKC)

5-HT2a

1-(2,5-dimethoxy-4-iodophenyl) 2-aminopropane (DOI)

5-HT2a agonist

ketanserin and ritanser

5-HT2a antagonist

DOI and related drugs are

hallucinogenic in humans

hallucinogenic effects of lysergic acid diethylamide (LSD) may stem from

its ability to stimulate 5-HT2a receptors

several drugs used to treat schizophrenia with reduced motor side effects act as

inverse agonists at 5-HT2a and/or 5-HTsc receptors

inverse agonists don't merely block a receptor, they

exert the opposite effect than an agonist would produce

serotonin drugs that stimulate cerebral vasoconstriction

for migraine headaches

5-HT1b/1d agonists (triptans)

serotonic drug that reduces activity in the pain pathway

5-HT1f agonist Lasmiditan (reyvow)

5-HT3 antagonists such as ondansetron (Zofran) , granisetron (Kytril) and palonosetron (Aloxi) can counteract

nausea and vomiting associated with chemotherapy and radiation treatments

sumatriptan (Imitrex or zecuity)

zolmitriptan (zomig)

frovatriptan (frova)

naratriptan (amerge)

triptans

most serotonergic neurons in the CNS are located in the

raphe nuclei

methodological approaches in human clinical research

- compare levels of 5-HIAA in CSF or 5-HT and 5-HIAA in postmortem brain regions with behavioral traits or neuropsychiatric disorders

- assess responses to SSRIs or receptor agonists and antagonists

- identify associations between psychiatric disorders and polymorphisms in the genes for SERT or for serotonergic receptors

para-chloroamphetamine

MDMA

5,6-dihydroxytryptamine (5,6-DHT)

and 5,7-DHT

serotonergic neurotoxins

lesioning of serotonin systems result in changes in

hunger and eating behavior, anxiety, pain sensitivity, and learning and memory

TPH2 knockout mice have a complete loss of

5-HT in the brain; can be temporarily restored with 5-HTP

most consistently observed behavioral effect of eliminating 5-HT

large increase in aggressive behavior measured by the resident-intruder test

reversed by 5-HTP plus carbidopa (AADC inhibitor)

AADC inhibitor that doesn't cross the blood-brain barrier - blocks AADC conversion of 5-HTP to 5-HT in peripheral tissues 5-HTP to 5-HT. This method permits more 5-HTP to be available to the brain.

carbidopa

other behaviors of TPH-2 knockout mice

more impulsive and compulsive

less anxious

have poor social communication and social behaviors, including maternal deficit

physiological deficits of TH+PH-2 knockout mice

poor thermoregulation

abnormal respiration, including apnea

abnormalities in the serotonergic system may play a critical role in some cases of

sudden infant death syndrome (SIDS)

____ has a key role in regulation of anxiety

5-HT

SSRIs are use dto treat

anxiety disorders, they target 5-HT1a receptors

(buspirone (buspar) vilazodone (viibryd))

in experimental animals, partial and full 5-HT1a receptor agonists have

anxiolytic effects

5-HT1a knockout mice show increased

anxiety-like behavior

experiments show that excitation of the serotonergic nerev terminals

increases 5-HT release, had an anxiolytic effect - increased time in open-arm of elevated plus-maze, inhibition of the terminals was anxiogenic

results of experiments that show excitation of serotonergic nerve terminals indicate the importance of?

postsynaptic 5-HT1a receptors in reducing anxiety

response to provocation, threat, or frustration; accompanied by anger or rage

reactive aggression

planned, to achieve a benefit

proactive aggression

neural circuit underlyijng reactive aggression in humans includes

cortical areas, striatum, amygdala, BNST, hippocampus, hypothalamus, and periaqueductal gray

what areas process threatening stimuli

amygdala and BNST

the amygdala receives sensory input from the ___, contextual input from the ____, and evaluative/regulatory inputs from the _____

thalamus

hippocampus

cerebral cortex

what is the serotonin deficiency hypothesis of aggression?

low CNS serotonergic activity is associated with hyperaggressiveness; supported by animal studies

the SSRI sertraline can

reduce anger and irritability in a variety of psychiatric disorders

relationship between 5-HT and aggression in humans may be

more complex

serotonin influences

hunger and eating behavior