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Re: NRIs are infact dopamine uptakin inhibitors ? zeugma

Posted by SLS on February 20, 2006, at 9:34:00

In reply to Re: NRIs are infact dopamine uptakin inhibitors ? SLS, posted by zeugma on February 20, 2006, at 6:15:08

I think we are getting our cortical wires crossed.

:-)

The point I was trying to make is that the dopamine found in the cortical areas we are talking about is not released into the synapses of NE neurons, but is mainly found just diffusing passively within the interstitial fluids (extracellularly), having been released by DA neurons elsewhere. It looks for any dopamine receptors it can find. This distant non-synaptic neurotransmission is sometimes called volume neurotransmission. It turns out that the NET is the only uptake pump in some areas able to clear this rogue dopamine. The rest is probably metabolized by catechol-o-methyltransferase (COMPT). Nevertheless, this diffused dopamine does affect the activity of these cortical areas and plays a role in regulating attention and working memory.

I guess the bottom line is that NE uptake inhibitors help to regulate the "tone" of dopaminergic neurons by sweeping up their mess for them. If the brooms break, the tone of DA neurons increases, leading them to become more easily stimulated by the messages they are meant to propogate.

Up until now, we have been talking mainly about the *reuptake* of synaptic neurotransmitters for reuse when we consider its inhibition by drugs. In this case, however, it is the *uptake* and mostly destructive clearance of heterogenous neurotransmitter that is at issue.

To complicate the issue, not all of the DA taken up by NE terminals is deactivated. Some of it still manages to make its way into protective storage vesicles to be released with the next NE action potential.


- Scott

 

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