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  • N&PD Moderators: Skorpio

Is this a good analogy for the stimulants?

TO the OP(didn't read other posts yet): Your analogy is a bit spot on, but also consiider that neurons, when damaged in the CNS, are usually permanently damaged -this is different in the PNS where damaged neurons can be restored- But damaged CNS neurons undergo a quick deletion response from your body- probably a protective mechanism to protect against aberrant neuronal activity.
BUT neurons also can GROW MORE densely and abundantly in the CNS if you do things like: Exercise, sex, listen to classical music - these things increase a protein called BDNF - Brain Derived Neurotrophic Factor - which grows your neurons (-troph means growth). Exercise greatly increases BDNF, and all marketed antidepressents that have been found to be effective, regardless of other mechanisms, increase BDNF.

Some drug-induced brain damage is also probably effecting FAT: fast-axonal-transporter which moves the vesicles of neurochemichals and BDNF throught the neuron. In Huntington's-Disease, the braid actually "corrodes" because the FAT cannot get BDNF to the parts of your brain because the FAT is genetically non-functional. AND SO HD patients have a brain that has it's matter shrunken or "eaten", almost like an alzheimers patients, except more with movement-disorder-areas.
 
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Cotcha Yankinov said:
Is this because because the presynaptic neuron has degenerated or because of adaptive changes?

I remember you've said the efficacy of 5-HT2A antagonism for Parkinson's disease related psychosis/hallucinations is probably due to 5-HT2A sensitization with Parkinson's. Is that because the presynaptic neuron might have degenerated, therefore with less typical axon serotonin release the 5-HT2A are very sensitive to volume transmission?

I suppose with loss of the pre-synaptic SERTs clearing the volume transmission related serotonin there could be more serotonin binding post-synaptically than before when you had pre-synaptic serotonin efflux but also presynaptic SERTs?
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NO, PD hallucinations are a result of medication that increases DOPAMINE which is the same chemichal that is overproduced in the brains of shizophrenics - that's why MEDICATED PD patients have psychotic symptoms at times, due to MEDICATION that increases DOPAMINE.
 
serotonin2A said:
Norepinephrine also makes a substantial contribution to stimulant effects.

I don't really understand why the analogy you proposed would be useful.

The comparisons are arbitrary and they don't really make the pharmacology easier to understand. Stimulants don't "borrow" transmitters from terminals -- a better analogy with amphetamine would be poking holes in the bottom of a water bottle so that the water leaks out. But even that would be silly because it doesn't really accurately reflect the pharmacology.
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NE doesn't really do shit to produce noticable effects- look at STRATTERA- it is all NE and does NOT DO SHIT. Now increased NE is responsible for a lot of drug-WD symptoms.
 
There are two subpopulations of TrkB receptor (target of BDNF binding), the low affinity one is involved in neuronal apoptotic regulation, whilst the high affinity one is responsible for the neurotrophic, antidepressant effects etc) also the location within the brain where BDNF is released is important, release/agonism in the hippocampus is antidepressant, and also memory enhancing, whilst in the prefrontal cortex it actually impairs memory.

Some ligands are selecive for high vs low affinity TrkB receptor subtypes.
 
serotonin2A said:
Supersensitivity is usually defined functionally, not on the basis of receptor number. In addition to changes in receptor expression, it could reflect downstream changes, eg, altered G protein coupling.
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Interesting. Do we know much about the possible downstream changes - as in, is it altered neurotransmitter concentrations that lead to development of altered signaling cascades, or is it more Parkinson's disease related in the sense of Tau/Amyloid beta interfering with the cell's function?

I guess I'm curious if the signaling cascades may be abberrantly altered with say, psychedelics and other neurotransmission modifiers, or if genuine Parkinson's disease pathology is required. Still trying to figure out the role of 5-HT2A in causing LTCs and HPPD, and why adverse MDMA effects (LTCs) so often coincide with HPPD, and why some people have mini-LTCs from psychedelics before their MDMA LTC.
 
Cotcha Yankinov said:
Interesting. Do we know much about the possible downstream changes - as in, is it altered neurotransmitter concentrations that lead to development of altered signaling cascades, or is it more Parkinson's disease related in the sense of Tau/Amyloid beta interfering with the cell's function?

I guess I'm curious if the signaling cascades may be abberrantly altered with say, psychedelics and other neurotransmission modifiers, or if genuine Parkinson's disease pathology is required. Still trying to figure out the role of 5-HT2A in causing LTCs and HPPD, and why adverse MDMA effects (LTCs) so often coincide with HPPD, and why some people have mini-LTCs from psychedelics before their MDMA LTC.
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Tau/ amyloid was, i thought, mostly Alzheimers
 
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