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Do they increase it, or is the effect mostly neutral?

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In its current form, this question can be answered in one sentence by a simple Google search. Can you be more specific and expand your question? –  yamad Jan 20 '12 at 13:00
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1 Answer

up vote 2 down vote accepted

Amphetamine and methylphenidate are not (direct) dopamine agonists.

Dopamine agonists are the substances that would specifically bind to dopamine receptors and activate them, thereby mimicking the effects of dopamine release.

Amphetamine/methylphenidate are so-called indirect sympatomimetics. This means that they stimulate the simpatyc nervous systems (with neurotransmitters noradrenaline and dopamine in CNS), but in indirect way: they don't bind to the receptors. Rather, they promote the massive neurotransmitter release from the presynaptic part. The released transmitter (DA, NA) then just diffuses to the postsynaptic membrane and binds to its own receptors.

There are some works done on investigating the effect of these substances on parasympatic system with acetylcholine as neurotransmitter.

Sympatomimetics like amphetamine generally lead to increase of acetylcholine release throurout the nervous system: in hippocampus and caudate nucleus, nucleus accumbens and generally in forebrain and cortex.

This effect of amphetamine is indeed in many cases mediated through dopamine receptors. Same time some direct dopamine receptor agonists were found to supress ACh release in some brain regions.

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