D-amphetamine Tolarance:Reduction in Dopamine or Reduction in Dopamine Receptors?

[forensic bob]

" In the presence of amphetamine, however, DAT has been observed to function in reverse, spitting dopamine out of the presynaptic neuron and into the synaptic cleft.[24] Thus, beyond inhibiting reuptake of dopamine, amphetamine also stimulates the release of dopamine molecules into the synapse"

Ok, assuming this is true, how does one's body react to the increased levels of dopamine in the synapse?

Is the excess dopamine(that should not be there in the first place):

A)returned to the presynaptic neuron from which it came.
or
B)metabolized and eliminated from the body.

If anybody can answer the question, it will bring me one step closer to understanding whether the tolerance one gains to the subjectively pleasent dopamine effects of d-amphetamine is the result of a down-regulation of receptors or simply a distruption in the ratio of Dopamine created vs. Dopamine Metabolized.

 

[any major dude]

I believe most long term stimulant users have a reduction in synaptic DA in the nucleus accumbens, IIRC. I'm pretty you'd see down regulation of DA (and possibly NE) receptors as well, though I don't explicity remember reading anything to that effect at the moment.

search pubmed.gov for things like "stimulant abuse disorder" and "amphetamine tolerance," that should give you a more definitive answer.

 

[forensic bob]

I believe most long term stimulant users have a reduction in synaptic DA in the nucleus accumbens, IIRC. I'm pretty you'd see down regulation of DA (and possibly NE) receptors as well, though I don't explicity remember reading anything to that effect at the moment.

search pubmed.gov for things like "stimulant abuse disorder" and "amphetamine tolerance," that should give you a more definitive answer.

I tried pubmed, didnt turn out well.

Regardless, do you believe that if one takes his medication under certain conditions, he might be able to lessen the reduction of DA in the nucleus accumbens and the downregulation of DA receptors (tolerance).

FOr example, if I were to take d-amph upon waking, go back to sleep, and then watch tv all day would the downregulation of DA and DA receptors be more significant than if I were ride my bike, study, or do any other activity that would normaly result in increased DA concentrations whilst not on adderal?

 

[MeDieViL]

Amphetamine has been shown to increase glutamate levels to the point of hyperexcitation. [1],[2],[3].
This glutamate efflux causes dopamine receptors to downregulate wich in turn leads to a dimished response to amphetamine. The most effective way to counteract this is by use of the NMDA antagonist memantine.

NMDA antagonists have been shown to upregulate dopamine receptors in the striatum[4][5][6]. Glutamate hyperactivity in ALS has also been associated with dopamine downregulation[7].

 

[Slapdragonx]

Basically, tripping on dissociatives will reduce or stop your tolerance.

 

[forensic bob]

nice, dxm for the sake of bettering my add. Amen to that.

 

[miconorphine]

would Sulbutiamine help as it increases dopamine receptor density

 

[any major dude]

FOr example, if I were to take d-amph upon waking, go back to sleep, and then watch tv all day would the downregulation of DA and DA receptors be more significant than if I were ride my bike, study, or do any other activity that would normaly result in increased DA concentrations whilst not on adderal?

I doubt that would make any substantial difference. The amount of DA the human body produces for even very strong stimuli pales in comparison to the amount of DA released from a modest dose of amphetamines

 

[Advaneuro]

WHen they describe amphetamine bonding to the DAT they are not reffering to a specific structure(pump) they are reffering more to the outward bound vesculiar transport system which is composed of multipule different proteins actinin for instance.The D2(slow dopamine,tonic) component is very real it increase working memory while significantly narrowing the processing context of central regions of the brain. Lower dose amphetamine is pref because D1 effects on nmda, this is reffered to as phasic dopamine(fast). D-amphetamine cycles up a cascade effecting multipule different system these include MOA-b once it has been methylated it binds with PEA to forming a tri,ring structure that may bind with sigmas 1& but more 2.
The downregulation i have heard is associated with glutamate based damage, specifically NMDA extrasynaptic receptors, nmda antagonist that dont block NR2A are very good to take with amphetamine, memantine is a good example of this.So you want to block nr2bs.

 

[sir_thizzalot]

Hmm, I tend to really study my drugs before using them, but didn't really look into DexAmps damage to Dopamine Receptors.
What could be permanent damage from using Dexamp once a week, dosing once in that day(and not a high rec. dose, I get off from less than most people it seems)? What about twice a week? I'm sure there's a thread just exactly on this, feel free to post it and I'll also go try to find it now!

 

[Advaneuro]

Amphetamine improves postsynaptic dopamine sites, this is observed by behavourial senistization, my mild use of stimulants has improved my motivation and personality while not using. But amphetamine cause oxidative stress particulary targeted to dopamine producing neurons(these are very specialised) this along with changes in other areas of the system make it hard not to use.

Use of amphetamine once a week will definitly have pronouced effects on your personality and mental function these can be both positive and negative. I have no knowledge of your situation, how you will use it,legality etc. You bear the consequence so you decide.
You wouldnt need to be very imaginative to get a script but it would cost a grand or two and would mean that you were diagnoised with a neurological condition(insurance price) for the rest of your life.

I strongly recommend not to use caffinine, in anything but the most moderate dose while using amphetamine.......
Magnesium(100mg++) is vital to take at or when you ingest this is because its a voltage dependent nmda channel blocker.
r-alpha lipolic acid and green tea extract with cocoa are a good idea.

 

[nods]

The problem with D-amp is it increases hormone output from the pituitary gland, this increases adrenalin and noradrenalin. The downside in stimulating the pituitary adrenal axis with any drug is a sharp decline in it's activity when the drug clears from the body. Depending on dosage you get physiological (and psychological) depression, this can last 24-48 hours, post D-amp use makes any activity a real drag, so you pop some more and in 30 mins your back in action, pretty soon many are using it everyday. Then another problem kicks in, in 2-3 weeks the body becomes more efficient at neutralising the drug, so you up the dose. After 2-3 months it may take 10 times the initial dose to get the same effect. Soon folks cannot operate without a daily fix of high dose amps. In the 1960's hundreds of thousands of people got into this drug addiction-thats why they were made Cll in 1970 and use dropped 70-80%.