Term
| Serotonin is synthesized from the amino acid... |
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Definition
| tryptophan (obtained from the diet) |
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Term
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Definition
| Tryptophan -> 5-HTP (by tryptophan hydroxylase - the rate limiting step). Then 5-HTP -> 5-HT (by aromatic amino acid decarboxylase AADC) |
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Term
| True/False: Trypophan hydroxylase only found in serotonergic cells |
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Definition
| TRUE (like tyrosine hydroxylase is only found in catecholinergic cells) |
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Term
| What kind of monoamine is 5-HT? |
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Definition
| 5-HT is an indoleamine (not a catecholamine like DA or NE) |
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Term
| True/False: 5-HT is found in plants, invertebrates, and vertebrates...it is phyolgenetically ancient. |
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Definition
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Term
| In mammals, where are high levels of 5-HT found? |
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Definition
| In the brain, lungs, and gut |
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Term
| The 2 types of tryptophane hydroxylase and their differences. |
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Definition
| TPH1 is found in the periphery while TPH2 is found specifically in the brain. (TPH1-/- mice express normal amounts of 5-HT in the brain but none in the periphery..show now behavioral differences from wildtype) |
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Term
| 5-HT is metabolized by _____ into _____ |
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Definition
| 5-HT is metabolized by Monoamine Oxidase A (MAO-A) into 5-hydroxyindoleacetic acid (5-HIAA) |
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Term
| MAO-A preferentially breaks down... |
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Definition
| MAO-A preferentially breaks down 5-HT but also NE and DA |
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Term
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Definition
| MAO-B breaks down phenylethylamines and benzylamines |
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Term
| True/False: MAO-A is present in the brain, MAO-B present in the rest of the body. |
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Definition
| FALSE...MAO-A and MAO-B BOTH are present in the brain AND throughout the body |
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Term
| MAO-A and MAO-B are encoded by two tightly linked genes on... |
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Definition
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Term
| 5-HT is packaged into vesicles by... |
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Definition
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Term
| What is the effect of para-chlorophenylalanine (PCPA) on rodents? |
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Definition
| PCPA irreversibly inhibits tryptophan hydroxylase...5-HT reduced by 80-90% for up to 2 weeks |
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Term
| Effect of dietary acute trypophan depletion (ATD) in humans?..what is it? |
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Definition
| ATD is a cocktail of large, neutral amino acids that compete with tryptophan for entry into the brain. It only lasts a few hours and is reversible. |
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Term
| Source of 5-HT projections in the rat brain |
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Definition
| Raphe nuclei in the brainstem |
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Term
The rostral group (B5-B9) in the rat brain projects (5-HT projections) widely to..
The caudal group (B1-B4) projects to.. |
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Definition
| The rostral group projects widely to the forebrain. The caudal group projects to the brainstem, cerebellum and spinal cord |
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Term
In humans, 85% of 5-HT cells are in _______ which projects to...
The other 15% of 5-HT cells are in ____ and project to... |
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Definition
| In humans, 85% of 5-HT cells are in the Rostral Raphe Nuclei (RRN), which projects to Cortical and Subcortical Regions. The other 15% of 5-HT cells are in the Caudal Raphe Nuclei (CRN) and project to the Brainstem and Spinal Cord |
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Term
| Dual 5-HT innervation of the forebrain by..and how do they differ? |
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Definition
| D and M fibers - They differ in their locations of 5-HT cell bodies.. D fiber cell bodies located in the dorsal raphe nucleus. M fiber cell bodies in the medial raphe nucleus. |
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Term
| Physiological functions of 5-HT |
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Definition
| Gut motility, vomiting, and vascular functions |
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Term
| How many serotonin receptor families and subtypes? Are they metabotropic or ionotropic? |
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Definition
| 7 receptor families (5-HT1 thru 5-HT7), 15 subtypes, and most are metabotropic, except for 5-HT3 |
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Term
| Activation of 5-HT1A receptors have what effect on the cell? |
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Definition
| 5-HT1A receptors are coupled to inhibitory G proteins..once activated, the G protein inhibits AC and hyperpolatizes the cell by opening K+ channels |
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Term
| What is the function of 5-HT1A in the raphe? |
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Definition
| In the raphe, 5-HT1A is a somatodendritic autoreceptor that decreases the firing rate of 5-HT neurons via feedback inhibition. |
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Term
| What is the function of 5-HT1A receptors in the forebrain projection regions? |
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Definition
| In the forebrain projection regions, 5-HT1A are found on the postsynaptic neuron and inhibit neuronal firing. |
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Term
High densities of 5-HT1A found in...
Low to none found in... |
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Definition
| High densities of 5-HT1A found in the frontal cortex, amygdala, hippocampus, and raphe. Low to none found in the striatum and cerebellum |
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Term
| Activation of 5-HT1B has what effect on the cell? |
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Definition
| 5-HT1B receptors work in the same way as 5-HT1A receptors...the G protein is inhibitory. The G protein inhibits AC and hyperpolarizes the cell by opening K+ channels |
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Term
| What are the inhibitory functions of 5-HT1B? |
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Definition
-Gi couples (inhibits AC and opens K+ channels)
-They act as TERMINAL autoreceptors (on axon terminals) which decreases 5-HT release in projection regions via feedback inhibitions.
-Also act as Presynaptic Heteroceptors (on NON-5-HT neurons)..they inhibit the release of DIFFERENT NTs (e.g.GABA) |
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Term
| 5-HT1B/1D/1F receptor agonists are used as... |
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Definition
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Term
| What is the effect of activating a postsynaptic 5-HT2A receptor? |
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Definition
| 5-HT2A is Gq-coupled..when the Gq protein is activated, it stimulates phospholipase C (PLC) |
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Term
| Highest expression of 5-HT2A receptors are on... |
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Definition
| Highest expression of 5-HT2A receptors are on glutamatergic pyramidal neurons ***but also on GABAergic interneurons |
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Term
| What kind of drug is LSD? What kind of drug is Clozapine? |
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Definition
| LSD is a 5-HT2A agonist. Clozapine (atypical antipsychotic) is a 5-HT2A antagonist. |
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Term
| What kind of receptors are 5-HT3A receptors? |
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Definition
| 5-HT3A receptors are ionotropic and are 5-HT Na+/Ca2+ channels |
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Term
| High expression of 5-HT3A receptors in the rat brain found in... |
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Definition
| the frontal cortex, cingulate, primary and secondary motor areas, spinal cord, and in peripheral nerves. |
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Term
| True/False: 5-HT3A receptors are expressed both by glutamatergic and GABAergic neurons. |
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Definition
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Term
| Antiemetic agents to treat nausea and vomiting during chemotherapy are what kinds of drug |
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Definition
| 5-HT3 antagonists (high density in the area postrema) |
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Term
Name Pathway and Function/Localization of the following receptor types:
5-HT1A.
5-HT1B. |
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Definition
5-HT1A:Gi/o coupled..Somatodendritic autoreceptors and postsynaptic receptors.
5-HT1B:Gi/o coupled..Terminal autoreceptors and Presynaptic heteroceptors (on non-5-HT neurons)
5-HT2:Gq-coupled..Postsynaptic receptors
5-HT3:Ionotropic(Na+/Ca2+)..Postsynaptic.
5-HT4,6,7:Gs-coupled..Postsynaptic receptors
5-HT5:unknown..mainly on astrocytes? |
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Term
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Definition
| Pindolol is a 5-HT1A antagonist that helps speed up SSRI action. |
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Term
| Why does it take weeks for SSRIs to begin to work? |
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Definition
| Probably due to the delayed down-regulation of 5-HT1 receptors. |
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Term
| Serotonergic, dopaminergic, and noradrenergic autoreceptors all inhibit their respective NTs by... |
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Definition
| using terminal autoreceptors that directly inhibit the NT release, and using somatodendritic autoreceptors which indirectly inhibit release by slowing the rate of firing of the neurons. |
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Term
| The synthesis of brain 5-HT in rats can be enhanced by the consumption of... |
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Definition
| low protein, high carb meals |
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Term
| In rodents, 5-HT2A agonists produce... In humans, 5-HT2A agonists produce... |
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Definition
| In rodents, 5-HT2A agonists produce head twitches while in humans they produce hallucinations (LSD) |
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