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36 Cards in this Set

  • Front
  • Back
Serotonin is under which class of monoamines?
What is serotonin synthesized from?
A dietary precursor called tryptophan, an amino acid.
What is the rate limiting step in serotonin synthesis? That is, what is unique for serotonergic neurons?
Tryptophan hydroxylase
What step is common to monoamines?
AADC - aromatic L-amino acid decarboxylase
What degrades serotonin?
MAO-A (Monoamine oxidase-A)
Provide all of the steps for the synthesis and degradation of serotonin.
Synthesized from L-Tryptophan by tryptophan hydroxylase into 5-HTP (L-5-hydroxytryptophan) which is converted into 5-HT or serotonin by AADC (aromatic L-amino acid decarboxylase). Serotonin is degraded by monoamine oxidase-A
Does turkey increase brain levels of tryptophan? Why or why not?
NO - turkey has low levels of tryptophan and competes with other amino acids to cross the blood brain barrier. You are more likely to become tired by eating lots of carbohydrates because this produces insulin which signals amino acid uptake from blood into cells but does not affect tryptophan. The result is a ratio of high tryptophan to low other amino acids that can now compete successfully to cross the BBB, synthesize into serotonin and be converted into melatonin.
What transporter is unique to serotonin?
5-HT transporter (5-HTT or SERT)
What allows vesicular transport of serotonin?
VMAT2, which is common to both serotonin and catecholamines.
What does vesicular storage of serotonin protect this NT from?
Breakdown by monoamine oxidase-A in the axon terminal.
Rostral Raphe
Consists of Dorsal and Median Raphe - ascending projection that consists of B6,7,and 8
Caudal Raphe
Descending projections directly to motor neurons and sympathetic nervous system - consists of B1-4
Dual ascending 5-HT projections (rostral raphe) are located in which part of the brain?
They innervate the forebrain structures.
Compare dorsal and medial raphe
Both (D & M fibers) are the site where projections originate from. They are morphologically distinct; dorsal raphe projections are more diffuse. They both have partially overlapping projection fields and varying degrees of 5-HTT expression (lower in D fibers). Correlated to susceptibility to MDMA neurotoxicity and perhaps indicates site of action of SSRI antidepressants.
Serotonin and repetitive movements
Increases in 200-500% in firing during repetitive movements such as chewing, licking, grooming. Direct application can increase amplitude of simple jaw reflex and increase the rate of repetitive locomotion such as swimming movements.
What is serotonin activity like during rest and during activity?
During rest, it is like regular, clock-like firing at low rates. During activity, it increases 10-30%.
What are two experimental methods of 5-HT depletion? (One for animals and one for humans)
Animals - 5,7 DHT - a neurotoxin that degrades serotonergic terminals and cell bodies. It can be applied to specific regions to target knockouts.
Humans - ATD (acute tryptophan depletion) A cocktail of large, neutral amino acids that compete with tryptophan for entry into the brain. It is transient (~few hours) and reversible
How can 5-HT application stop escape responses?
In descending 5-HT systems, the application of serotonin can stop escape responses evoked by stimulation of the PAG.
How can serotonin decrease activity in the amygdala and its role with fear?
If you give humans ATD - there is a decreased amygdala response to fear.
What role does 5,7 DHT have in animal's amygdala?
Injection of this into the amygdala reduces expression of anxiety in animal models such as the conflict test, where thirsty animals receive occasional shocks when drinking.
What role does 5-HT have with punishment?
In people who have lowered 5-HT levels, there is enhanced sensitivity to punishment. In the experiment of predicting reward and punishment, people with lowered 5-HT levels had a lower error rate for punishment, but not reward.
5-HT1A receptors
Have dual inhibitory functions. They are Gi-coupled (inhibits AC, hyperpolarizes the cell by opening K+ channels)
5-HT1A in raphe
Somatodendritic autoreceptor that produces feedback inhibition (a decreased firing rate of 5-HT neurons)
5-HT1A in forebrain projection regions
Postsynaptic receptor - inhibits neuronal firing
5-HT1B receptors
Located in different regions on the neuron. They are also Gi-coupled receptors
5-HT1B on axon terminals
terminal autoreceptors that produce feedback inhibition (decreases 5-HT release in projection regions)
5-HT1B on non-5-HT neurons
Presynaptic heteroreceptors that inhibits release of different NTs (such as GABA)
Postsynaptic 5-HT2A receptors
Gq-coupled -> stimulates phospholipase C. Highest expression on glutamatergic pyramidal neurons (but also on GABAergic interneurons).
LSD and Clozapine (atypical antipsychotic)
LSD - 5-HT2A agonist
Clozapine - 5-HT2A antagonist
Distribution of 5-HT receptors in the human brain
Different 5-HT receptors have unique distribution patterns in the brain.
5-HT3 receptors
Only ionotropic 5-HT receptors. Pass Na+/Ca2+ ions. Play a possible role in anxiety.
Serotonin 5-HT3 receptor antagonist used in chemotherapy, which blocks nausea and vomiting
Major class of antidepressants also used in treatment of anxiety disorders. They inhibit 5-HTT and lead to increased 5-HT levels in the synapse. Effects can take weeks.
A 5-HT1A antagonist that enhances and speeds up SSRI action.
Reuptake enhancers that function as antidepressants - effects are immediate.
Genetic polymorphism in the 5-HTT gene
Alters levels of 5-HTT transcription. Homozygotes for the short allele have lower reuptake and show increased incidence of depression after stressful events. Leads to lower levels of 5-HT perhaps due to long term adaptations. The actual coding sequence is the same, difference is in the length of a repetitive upstream promoter.