long term effects of ADD meds (neurochemically and otherwise)

[ebola?]

okay...check out this:


Title:
Can a therapeutic dose of amphetamine during pre-adolescence modify the pattern of synaptic organization in the brain?

European Journal of Neuroscience. Vol 18(12) Dec 2003, 3394-3399.
Blackwell Publishing, United Kingdom

Abstract
Stimulant drugs such as amphetamine have, for many decades, been the drugs of choice in the treatment of children with attention-deficit/hyperactivity disorder. In the present study we investigated whether repeated exposure of a low dose of amphetamine to juvenile rats could induce long-term morphological alterations in the prefrontal cortex. In addition, to assess possible behavioural consequences of prolonged exposure to this drug, we examined whether changes in the motor response to various dopamine agonists occurred after this treatment. We found that this dose of amphetamine promotes plasma concentrations of amphetamine sulphate in juvenile rats to levels corresponding to the clinical range used for children with attention-deficit/hyperactivity disorder. This treatment produced an increase in dendritic length and branches of pyramidal neurons of the medial prefrontal cortex, but not in the nucleus accumbens. Interestingly, amphetamine pre-treatment did not alter the motor response to various dopamine agonists, including amphetamine. These data suggest that clinical doses of stimulant drugs may be acting as a trophic support at the glutamatergic synapses, thereby enhancing dopamine-glutamate interactions in the prefrontal cortex. (PsycINFO Database Record (c) 2004 APA, all rights reserved)


Any speculations on the ramifications of these types of changes in humans? Also, pertinent meta-analyses I've seen have argued that stims. tend to lose their efficacy (and have overall negative effects) for ADD after a matter of years, but are still quite effective in the window of 24 months of a typical daily regimen.

ebola

 

[lizness]

Altered dopamine-glutamate interactions in the prefrontal cortex are implicated in diseases such as schizophrenia so maybe these patients would be more susceptible to developing these? This is pure speculation though!

I think it's interesting that the rats didn't develop behavioural sensitisation to dopamine agonists after chronic amphetamine treatment. This is a commonly used preclinical model for amphetamine addiction is it not? It suggests that the doses of amphetamine used to treat ADD are not high enough to produce sensitisation/addiction (obviously, or amphetamines would not be used to treat ADD!)

 

[ebola?]

>>Altered dopamine-glutamate interactions in the prefrontal cortex are implicated in diseases such as schizophrenia so maybe these patients would be more susceptible to developing these? This is pure speculation though!
>>

Right, although its better than a shot in the dark, to be sure. Still, do we know what KIND of changes would be implicated in schizophrenia? Of course, not all changes are dammage per se.

>>This is a commonly used preclinical model for amphetamine addiction is it not? It suggests that the doses of amphetamine used to treat ADD are not high enough to produce sensitisation/addiction (obviously, or amphetamines would not be used to treat ADD!)>>

To be frank, I think amphetamines would still be used often even if addiction were a large problem. We don't wanna give our children individualized instruction (or at least our rulers in the state dont wanna foot the bill), so we give them pills and shove them in a box. Pharmaceutical firms only further fuel the fire for their profits.

ebola

 

[BilZ0r]

I think the dose was too low to induce sensitization. Also, inducing sensitization is dependent on numerous things, and in the case, location. I geuss they gave the "chronic" doses in the animals' home cage, but after the challange dose, they would have put them in the light box, or whatever the measured locomation with. You often wont see sensitization after things like that.

 

[Synapse999]

This is probably one of the best sources i have read regarding studies and such of that nature.


With the many different variables and situations that make up the concept of Sensitization, i learned quite a bit.
That, and about actual reversal of tolerance and deSensitization of sorts. From continous/intermittent doses.
They have a few clips on there, showing animals in a psychosis, or in different states depending on there example.
Includes studies, tech information about the presynaptic alterations etc. for adhd as well.

Animals are mostly used in many of these tests, to explain DA systems role on enviorment and doses. Like, the natural behavior for primates is to search for food. they will doit for days straight...if they are trained to press a bar for food..eventually in cases they have stereotyped schitzo behavior.
where they will continously search,investigate, etc. around the bar. now giving them reinforcement that the actual reward of pressing it for food did.
Due to accidental conditioning.

As someone who has been on daily dextroamphetamine, mostly in high-doses. for over 2 years now. I was able to relate/understand and explain alot of things.

Psychopharmacology.- Amphetamines


This is a study with dextroamphetamine and baboons etc. showing differences in methylphenidate etc. has decent tables and charts from PET scans. going to be reading it now.
Amphetamine-Induced Dopamine Release

This is newer study, havnt read...specfic to that.
Role of adenosine receptors in amphetamine sensitization