Posted by Michael Bell on March 5, 2003, at 10:59:53
In reply to Re: Dopamine agonists » Michael Bell, posted by not exactly on March 5, 2003, at 2:56:34
> > ... I actually disagree with people who claim dopamine levels are too low. Quite the opposite, I think we have high levels of dopamine but LOW NUMBER OF RECEPTORS/POOR TRANSMISSION.
> > ... people with SP have substantially less number of D2 receptors than normal subjects, and they speculate that this may be a result of downregulation due to chronically high levels of dopamine in the brain.
>
> Fascinating! I really like this theory, because it finally explains some things that never made sense before. For example, it would explain why I responded so well to Mirapex (a dopamine agonist) but after a while it completely "pooped out". Perhaps at first it improved the stimulation of the too-sparse dopamine receptors, but eventually there was a compensatory further downregulation. MAOIs would probably have the same limitation. What sort of drug would enhance dopamine transmission without causing this compensation? A dopamine reuptake inhibitor? A pre-synaptic antagonist? Seems like what is really needed is a med that interferes with the downregulation compensation process.
>
> And how could one reverse the downregulation that had already taken place? Would REDUCING the dopamine levels cause the receptors to become more sensitive? Maybe an antipsychotic/neuroleptic would, in the long term, induce an UPregulation? What do you think?
>
> - Bob
>Bob, it's so interesting what you've added to the thread regarding your experiences. I also believe that when we take drugs that increase dopamine, this allows the reduced number of receptors to be stimulated by the increased dopamine - for a while. Then the brain registers this excess dopamine, and further downregulates the number of receptors, hence the poop-out effect. I too am trying to find out about drugs that effect dopamine transmission itself and not just increase overall dopamine levels.
Regarding upregulation - interestingly, in people with Parkinson's disease, studies have shown that as the number of dopamine cells gets lower, the brain upregulates the number of receptors to compensate. However, eventually the number of cells get so low (80% reduction) that even having a higher number of receptors doesn't help. So there is probably a way to increase the number of dopamine receptors, but safety is a big issue.
poster:Michael Bell
thread:205134
URL: http://www.dr-bob.org/babble/20030301/msgs/206110.html