Posted by KaraS on December 18, 2004, at 17:52:36
In reply to Re: SSRI/dopamine antagonism, posted by rod on December 18, 2004, at 8:27:44
> Hi,
>
> Maybe this has been said before in this thread, because I havent read all posts, but I personally find this very interesting: Something called "Transmitter relocation"
>
> ---------------
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12065714
>
> The selective serotonin reuptake inhibitor citalopram induces the storage of serotonin in catecholaminergic terminals.
>
> Suarez-Roca H, Cubeddu LX.
>
> Pharmacology Section, Instituto de Investigaciones Clinicas, School of Medicine, University of Zulia, Maracaibo, Venezuela.
>
> We investigated whether selective inhibition of serotonin (5-hydroxytryptamine; 5-HT) transporter with citalopram leads to accumulation of 5-HT in catecholaminergic neurons. In the rabbit olfactory tubercle, citalopram (1-10 microM) inhibited [(3)H]5-HT uptake; however, the maximal degree of inhibition achieved was 70%. Addition of nomifensine (1-10 microM) was required for complete inhibition of [(3)H]5-HT uptake. In slices labeled with 0.1 microM [(3)H]5-HT, cold 5-HT (0.03-1 microM) induced a large increase in the efflux (release) of stored [(3)H]5-HT, an effect blocked by coperfusion with 1 microM citalopram. Similar concentrations (0.03-1 microM) of norepinephrine (NE) or dopamine (DA) failed to release [(3)H]5-HT. When labeling with 0.1 microM [(3)H]5-HT was carried out in the presence of citalopram, 1) low concentrations of 5-HT failed to release [(3)H]5-HT; 2) DA and NE were more potent and effective in releasing [(3)H]5-HT than in control slices; 3) coperfusion of NE, DA, or 5-HT with citalopram enhanced the release of [(3)H]5-HT induced by the catecholamines but not by 5-HT; and 4) coperfusion of NE or DA with nomifensine antagonized NE- and DA-evoked [(3)H]5-HT release, with a greater effect on NE than on DA. These results suggest that in the rabbit olfactory tubercle, where there is coexistence of 5-HT, NE, and DA neurons, inhibition of the 5-HT transporter led to accumulation of 5-HT in catecholaminergic terminals. Thus, during treatment with selective serotonin uptake inhibitors (SSRIs), 5-HT may be stored in catecholaminergic neurons acting as a false neurotransmitter and/or affecting the disposition of DA and/or NE. Transmitter relocation may be involved in the antidepressant action of SSRIs.
>
> PMID: 12065714 [PubMed - indexed for MEDLINE]
>
> ------------------
>
> Does anybody know if 5-ht in dopaminerigc neurons cause similar neurotoxicity like (as far as I know) MDMA induced serotonin cell death via dopamine deamination in serotonergic nerves storage vesicles?
>
> I am wondering if my years of SSRI treatment (which caused overall worsening) are responsible for my resistand depression now (which is linked to a hypodopaminrgic state in my opinion. Also my doc thinks there is something wrong with my dopamine receptors)???
>
>
> bye
> Roland
Hi Roland,Interesting abstract. I've been wondering if several years usage of SSRIs has done the same thing to me. I have no drive or motivation though I've been off of the SSRIs for a few months now. (I had none while I was on them either.) When I try to add in dopaminergics like Ritalin, selegiline (and a couple of holistic ones), I get put to sleep. If I take it for a few days, I start to feel sick. Something is definitely wrong.
Dr. Jay Goldstein theorized that hypersensitive dopamine autoreceptors could be the problem - at least for some people. I don't know for certain that is my problem but I do think that the problem is related somehow to faulty dopamine production or utlization.
I don't like to think too much about whether it was caused by the SSRIs. It's too upsetting. I'm just trying to figure out what to do about it now. There aren't many things out there now that can downregulate the DA autoreceptors but I am going to try them next.
K
poster:KaraS
thread:428740
URL: http://www.dr-bob.org/babble/20041217/msgs/431363.html