Agonists vs re-uptake inhibitors?

[NorthernNinja]

Are re-uptake inhibitors less likely to reduce long-term depletion of the respective neurotransmitters than agonists? For example do SSRI's reduce long-term depletion levels of serotonin, if so is it less than serotonin agonists do? Same with noradrenaline and dopamine i.e. is Ritalin (a dopamine and noradrenaline re-uptake inhibitor I think) less likely to reduce long-term levels than an agonist of these neurotransmitters (I think amphetamines)?

My logic is if you are inhibiting re-uptake then you are still producing your own neurotransmitters just not losing as much. Whereas when you are giving them to your brain you will start producing less of you own (like steroid users with testosterone).

This is all based on my logic and minimal scientific knowledge so I would be grateful if anyone could give me some information.

[painstaking]

They are the same. The effect is the same if you think of the mechanism at work. I most cases, your body exhibits negative or positive feedback loops. That is to say, with more activation of the receptor or presence of the substance, it will signal back that there is a ton of that chemical, and you need to slow production. Or, you are lacking an effector, and signals are sent back to say, hey you need to produce more. So when you inhibit breakdown of the substance as is the case with MAOI's or reuptake with SSRI's, it is still active and thus your body still thinks that you are producing too much.

[etinin]

It really depends on what substances we're talking about. Though the endogenous chemicals are expected not to be significantly addictive, there may be exceptions. Some agonists are more powerful than the native chemical and are more addictive. Cocaine and meth, for example, are significantly more addictive than methylphenidate. Cocaine acts both directly at serotonin receptors and as reuptake/transport inhibitor. But amphetamine is only marginally more deleterious than methylphenidate. You can't really generalize; the comparisons must be made individually.

And you can't really talk about serotonin agonists, for example, since the most common ones are anti-emetics and psychedelics, which are not addictive at all. Serotonergic or dopaminergic ergot alkaloids are not addictive either.

[painstaking]

@etinin I may have missed something, but was the OP asking about addiction?

I thought the question had to do with depletion of neurotransmitters with reuptake inhibitors or through enzyme inhibition of the breakdown versus pure agonism.

[etinin]

Erm, true, I didn't read the post, properly xD

The answer is that it depends as well. Theoretically, it shouldn't make real difference because the body doesn't care where the agonism comes from, as was said by @painstaking . But some types of receptor activation cause the release of neurotransmitters.
The examples which come to my mind are pseudoephedrine releasing catecholamines and MDMA releasing serotonin, but other drugs surely do the same to a lesser or bigger aspect. That kind of action surely induces faster depletion of neurotransmitters. For most drugs, though, depletion isn't really a significant aspect. Receptor up and down-regulation is the most significant mechanism involved in long-term issues, which is why dependence came to my mind. The feedback loops such as the ones mediated by alpha-2 receptors are fast-acting and the body doesn't generally get "lazy" like it does with steroid usage.