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Do biogenic amines produce fast or slow transmission in neurotransmitters?
slow
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What kind of structure does Serotonin have?
indoleamine structure
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What converts tryptophan to 5-hydroxytryptophan?
tryptophan hydroxylase
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What is the molecular precursor to serotonin and what is the difference between the two molecules?
- 5-hydroxytryptophan
- serotonin is the decarboxylated form of 5-hydroxytryptophan
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What happens when there is serotonergic dysfunction in the CNS?
- depression
- anxiety
- OCD
- panic attacks
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How much of the brain is composed of serotonin pathways?
<1%
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Where do serotonin pathways come from and go to?
from ralphe nuclei and go to cortex (& down spinal cord)
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What is the pre-synaptic release modulating receptor in serotonin pathways?
5-HT1A
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What is "SERT"?
Plasma Membrane Serotonin Transporter: it removes serotonin from the synaptic cleft
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What are four common TCAs?
- amitryptiline
- imipramine
- clomipramine
- doxepin
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What does TCA stand for?
Tri-cyclic Antidepressants
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What are 6 common SSRI's?
- fluoxetine
- paroxetine
- fluvoxamine
- sertraline
- citalopram
- escitalopram
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What does SSRI stand for?
Selective Serotonin Reuptake Inhibitor
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What is depression the result of?
Reduced levels of biogenic amines in the CNS
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What are two discrepancies in the biogenic amine theory?
- Drugs take 2-3 weeks to work, even though the molecular aspect is working in several days
- Not all anti-depressant drugs inhibit transport of 5-HT or NE or MAO
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What does the updated biogenic amine theory say?
- That first there is receptor signalling dysfunction
- Then there is receptor supersensitivity and that drugs chronically work to reverse this
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Describe SSRIs and their effects on 5-HT1A.
Acutely: elevates Serotonin in Dorsal Raphe Nuclei and causes activation of 5-HT 1A Receptors. This causes a decrease in firing of the serotonergic receptors. Meanwhile SSRIs increase serotonin release in the forebrain. The combination of decreased firing and increase release is canceled out acutely.
Chronically: eventually cell bodies in the Dorsal Raphe Nuclei are normalized and normal firing resumes. Now, the SSRI can act in the forebrain unimpeded and increases the release of biogenic amines.
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How do the short and the long alleles of the 5-HTT gene differ with one another?
- They differ with respect to expression of the transporter and therefore serotonin uptake
- People with the s- or ss copies of the 5-HTT gene mean decrease in 5-HTT, increase in synaptic 5-HT, increase in excitatory 5-HT receptorsIn other words, people with the ss alleles are more likely to develop depression under similar stress factors
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What is the effect of high expression of the 5-HT1A Receptor?
increase in inhibition at somotodentritic sites, decreasing frequency of action potentials, decreasing release of serotonin (biogenic amines), increasing behavioral despair (depression)
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Will a neuron that has high expression of 5-HT1A receptors respond well to fluoxetine?
Nope
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What is the difference between the serotonergic dysfunction of depression and OCD?
- anatomy really
- orbitofrontal cortex is where the problem for OCD lies
- Pre-frontal cortex is where the problem for depression lies
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What is attributed to the enhanced release of serotonin in the orbitofrontal cortex?
densensitization of terminal 5-HT1B Receptors
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Why do SSRIs have fewer side effects than TCAs?
because SSRIs, such as fluoxetine, have little to no affinity for alpha1, histamine, and muscarinic receptors
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What is the locus ceruleus associated with in the brain?
noradrenergic pathways
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How many subtypes of noradrenergic receptors have been demenstrated in the brain?
- 8:
- alpha1A, 1B, 1C, 2A, 2B, 2Cbeta1, 2
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What role do adrenergic receptors play in the CNS?
regulation of mood, vigilance, and cardiovascular function
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Which pathway of catecholaminergic neurons degenerates in PD?
Nigrostriatal pathway
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Which dopamine pathways constitute the reward pathways of the brain?
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What controls pro-lactin release?
dopamine projection from the arcuate nucleus of the hypothalamus to the intermediate lobe of the pituitary
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Where do the reward pathways of the brain originate?
ventral tegmentum
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Describe the dopaminergic synapse
- Well, dopamine is synthesized from tyrosine->L-Dopa->Dopamine.
- Dopamine is transported into vessicles whose formation is regulated by synthesis modulating autoreceptorThere is also a release modulating autoreceptorfinally there are Ca++ channels that determine when the vessicles should be released
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How is the affinity for D2 Dopamine receptors related to the anti-psycotic dose?
They are directly related. The greater the affinity, the less the dose
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Describe the mesolimbic dopamine rewards loop.
- Well, it starts in the ventral tegmentum whose axon projects to the Nucleus Accumbens. These are the rewards when NT is released and there is also a -feed back loop from the nucleus accumbens and interneurons that project back to the ventral tegmentum
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Where do opiods and alcohol affect the rewards systems?
On the somatodendritic parts of the interneuron, nucleus accumbens and the synapses to the cortex
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Where can you find cholinergic nuclei in the brain?
No where in particular, they are very wide spread
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Does Nicotine affect the rewards circuitry?
Yes
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