Posted by SLS on April 28, 2009, at 7:38:15
In reply to Re: Dopamine depletion: A myth?, posted by brot on April 27, 2009, at 20:43:41
Hi.
Thanks for posting this.
This sounds like a reasonable mechanism by which dopamine depletion could occur. If 5-HT makes it past the outer cell membrane, it most likely will end up in the synaptic vesicles and displacing DA, as I believe the VAT2 is not selective for any one amine. It would be nice to see if there is an upregulation of dopamine receptors to compensate for this lack of dopamine. I think that would go a long way to supporting the dopamine depletion theory.
- Scott
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> http://www.ncbi.nlm.nih.gov/pubmed/12065714?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
>
> 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.
poster:SLS
thread:889604
URL: http://www.dr-bob.org/babble/neuro/20090129/msgs/893231.html