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Re: SSRI/dopamine antagonism

Posted by rod on December 18, 2004, at 8:27:44

In reply to Re: SSRI/dopamine antagonism » Mistermindmasta, posted by zeugma on December 15, 2004, at 13:33:30

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"

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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]

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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


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poster:rod thread:428740
URL: http://www.dr-bob.org/babble/20041217/msgs/431169.html