Does anyone know what sort of negative feedback there is to a state of dopamine surplus? I always assumed it involved some kind of downregulation, thinking along the lines of receptor downregulation, and maybe reuptake channel/MAO-A/catechol-o-methyl transferase upregulation. But I just saw a mechanism of neurotransm. desensitization mentioned that I hadn't seen before, on a page discussing MDMA: "A few hours later, there is a decrease in serotonin levels, amplified by the reduced activity of tryptophane[sic] hydroxylase, the enzyme responsible for synthesizing serotonin." Could there be an analogous system for dopamine? Is tyrosine hydroxylase deactivated by dopaminergic overstimulation? I can't find any literature on the subject. I'm damned curious as to how it the feedback works*, if it does, and if a chemical can be designed/found that can inhibit this inhibition, mitigating the nasty rebound from dopaminergics might be possible. Something which could have application in those who take methylphenidate (ritalin) for half the day and become increasingly dysfunctional in the evenings. lates, cotarded. *p.s. I'm guessing it's a presynaptic receptor that initiates a second messenger response... but I still can't find information. edit: had accidentally said mao-a/catechol... etc. downregulation when I meant upregulation.