CH. 6 Serotonin Flashcards
how is serotonin system wired
cell bodies in the raphe nucleus (B7, B8)
axon projections similar to NE, more than DA
what type of monoamine is serotonin
indolamine
how is serotonin synthesized
tryptophan becomes 5-HTP
5-HTP becomes 5-HT (serotonin)
what enzyme converts tryptophan to 5-HTP
tryptophan hydroxylase
what enzyme converts 5-HTP to 5-HT?
AADC
what other NT does AADC enzyme work on?
dopamine
what types of cells is tryptophan hydroxylase found in?
only serotonergic ones
what does PCPA do?
irreveresibly inhibits tryptophan hydroxylase to prevent 5-HT synthesis
which step in serotonin synthesis is the rate limiting one?
tryptophan to 5-HTP vua tryptophan hydroxylase
what is 5HT synthesis dependent on? why?
the ratio of tryptophan to other amino acids in the blood
they use the same transporter across the BBB so they compete for it
how can you indirectly reduce 5TH synthesis?
by giving aa cocktail not containing tryptophan
what kind of diet would increase tryptophan ratio in the blood? why?
high carb
increased insulin removes aas except tryptophan from blood for protein synthesis
what kind of diet would decrease tryptophan ratio in the blood? why?
high protein
liver activation starts protein synthesis who mainly use tryptophan
what behavioural effects can reducing serotonin have
depression remission
impaired impulse control
vesicle transporter protein for 5HT
VMAT2
what kind of autoreceptors does serotonin have? what do they effect?
presynaptic- reduce 5HT vesicle release
somatodendritic- slow firing rate
how is 5HT removed from the synapse?
by serotonin reuptake transporter
what is the metabolite of 5HT
5-HIAA
what enzyme metabolizes 5HT?
MAO
what drugs work like amphetamines but are more selective for serotonin? how are they similar to amphetamines?
fenfluramine
MDMA
reverse reuptake transporters
fenfluramine effect
appetite surpression
cardiovascular effects
MDMA use/effects
recreational drug
euphoria
therapeutic for PTSD
what do SSRIs do?
blocks SERT
example of an SSRI
fluoxetine
what are SSRIs treatment function?
antidepressants
how many 5HT receptor sub types are there? how many families?
14
7
which receptor familiy is not metabotropic?
3
what is the selectivity of available drugs like on serotonin receptors?
selective across families, non-selective within families
what is 5HT1a receptors function?
inhibits cAMP
hyperpolarizes cell (increase opening of K+ channels
where in the brain are 5HT1a receptors postsynaptic?
forebrain regions
where in the brain are 5HT1a receptors somatodendritic autoreceptors?
raphe nucleus
5HT1a receptors agonists
8-OHDPAT
Buspirone
what 5HT1a receptor agonist is a full agonist?
8-OHDPAT
what 5HT1a receptor agonist is a partial agonist?
buspirone
what do 5HT1a receptor agonists do?
stimulate postynapse
reduce 5HT release
5HT1a receptor antagonist
WAY-100635
5-HT1b/d receptor function
presynaptic autoreceptor
5-HT2a receptor function
postsynape receptor activating the phosphoinositide 2nd messenger system
what other receptor is the 5-HT2a receptor similar to?
a1 adrenergic receptor
5-HT2a receptor agonist
DOI
DOI effect
hallucinogenic
5-HT2a receptor antagonist
ketanserin
what is the general overall function of serotonin
to surpress certain patterns of behaviour
how to investigate serotonin function in humans
compare CSF 5-HIAA metabolites with traits/disorders
response to receptor agonists/antagonists, SSRIs
correlate disorders and SERT/5-HT receptor genetic polymorphisms
how to investigate serotonin function in animals
lesion 5-HT neurons
KO different 5HT receptors
delete 5-HT producing enzyme
psychopharmacological studies
studied functions of serotonin
satiety
anxiety
aggression
impulsivity
serotonin’s role in hunger
acts as short term satiety signal
increases as we eat
what brain area is serotonin using to affect hunger
disinhibits paraventricular hypothalamus neurons
what causes hypophagia
SSRIs
5HT releasers
5HT1b/2c receptor agonists
how do SSRIs shift hunger
reduce food consumed per meal
shift preference away from fatty foods
what causes hyperphasia
reducing 5-HT release
5HT1a agonists (autoreceptor)
how does 5-HT1a postynaptic receptor affect anxiety
activation reduces anxiety
what does buspirone treat
anxiety
how do 5HT2a/2c receptors affect anxiety
increases anxiety
what brain region is 5HT modulating for stress?
BNST
how does serotonin affect aggression?
low serotonin increases aggression
how is aggression tested in animals
resident-intruder paradigm
what role do 5HT1a/b receptors have on aggression
reduce aggression through actions on the postsynapse
how does serotonin affect impulsivity
controls ability to put the brake on impulsive responses
what receptor is responsible for reducing impulsivity
5HT2c