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Old 08-02-2008, 13:49
candy_kid candy_kid is offline
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amphetamine dxm tolerance and learning

As I'm sure many know, amphetamine tolerance can (theoretically?) be reduced with the use of NMDA antagonist drugs such as dxm and ketamine. Based on this info, swim typically adds an NMDA antagonist if using amphetamines for any extended period. However, he's not so sure any more if this is a good idea; at least when using for school.

I found this article below which talks about synaptic plasticity caused by dopamine. This is dopamine's ability to strengthen bonds between neurons, a process that is used in learning and memory. The idea behind taking amphetamines for non recreational purposes is typically to help with school work, so in the case of non recreational use one would regard this plasticity as a positive feature.

According to this article, NMDA receptor activity is responsible for dopamine-related plasticity. Deactivating NMDA receptors with NMDA antagonists if I'm reading into this properly would seemingly reduce dopamine-related plasticity and in turn reduce the effectiveness of amphetamines on learning.

If this is in fact the case, it might be good get the info out there so nobody reduces their performance unknowingly; of course preventing tolerance would still be an issue. I'm mostly just curious if anyone has any thoughts on the matter right now, like, is this a realistic situation? would the reduction in learning be small enough that its still worthwhile? Does anyone have any friends who might have anecdotal evidence in either direction? did rambo suck or was it awesome because it was so bad?

"According to Schuman, it was known that dopamine influenced the strengthening of synaptic connections among neurons. It was also known that such strengthening, or plasticity, involved activation of protein synthesis in the dendrites, which somehow led to enhanced activity of other kinds of neurotransmitter receptors. However, she said, the mechanism by which dopamine influenced such local protein synthesis and triggered plasticity was not known."

"The researchers also demonstrated a link between dopamine-related plasticity and NMDA receptor activity. They found that when they blocked NMDA receptors, the dopamine-regulated synthesis of GluR1, as well as enhanced synaptic transmission, were blocked. “This experiment showed that there may be some specificity to dopamine's actions, at least in how it stimulated local protein synthesis,” said Schuman. “You may need both dopamine release and functional NMDA receptors to trigger protein synthesis and plasticity.”"

http://nootropics.com/misc/dopamine.html

Last edited by candy_kid; 08-02-2008 at 14:17.
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Old 08-02-2008, 16:00
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jazzmetalguitar jazzmetalguitar is offline
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Re: amphetamine dxm tolerance and learning

Inquistive, and SWIM is surely not a neurologist, but he thinks SWIY is failing to distinguish amphetamines affinity to D3 dopamine receptors, as well as the receptors of epinephrine and norepinephrine, and the dopamine system as a whole. In SWIM's understanding, amphetamine's drive and energy, to which he attributes the increased "learning skill," pertains only to the instantaneous effects and excitation of the given receptors and that this is independent from plasticity. This plasticity, under Hebbian theory, pertains to the neurons "learning" activation patterns which is the theoretical origin of memory. The plasticity itself is the fact that once stimulation occurs the synapse becomes more sensitive to this stimulation and thus can remember it better. So, in reference to the given article, the synapses remember how the drug stimulates and excites the receptors.

But...SWIM has not slept in days so don't quote him...
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