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Re: Tianeptine: Effective Tolerable Antidepressant

Posted by Shawn. T. on August 2, 2002, at 1:04:35

In reply to Re: Tianeptine: Effective Tolerable Antidepressant, posted by cybercafe on August 1, 2002, at 8:19:17

That's an interesting question; I initially thought that I would be unable to answer it. I'll start with tianeptine. The following may or may not be exactly what happens, but it seems to make some sense.

"The results support the hypothesis that 5-HT(1B)
receptors within the VTA can function as
heteroreceptors to inhibit GABA release(1)."

"Overall, the results of this study suggest that
terminal DA release in the ACB is under tonic GABA
inhibition mediated by GABAA (and possibly GABAB)
receptors, and tonic cholinergic excitation mediated by both muscarinic and nicotinic receptors. Activation of GABAA (and possibly GABAB) receptors within the ACB may be involved in the feedback inhibition of VTA DA neurons (2)."

Increasing serotonin reuptake will reduce the amount of serotonin that is usually available to 5-HT1b receptors. This does not mean that it will not be activated, only that it will be activated less often. That means that the receptor will not be desensitized as easily. (I would say that tianeptine could possibly have effects on 5-HT-moduline, although that is not for certain. If it does, that could possibly explain another mechanism of 5-HT1b sensitization.) So the normal activation of inhibitory 5-HT1b heteroceptors on GABA neurons in the ventral tegmental area will be more difficult to disrupt due to tianeptine. That would result in a net increase in the availability of dopamine to the nucleus accumbens. As for the SSRI's, they do not increase dopamine in the nucleus accumbens. You may be thinking about what happens when serotonin is injected directly into the accumbens.

Fluoxetine (Prozac):
"In conclusion, the 5-HT-induced facilitation of NAc DA neurotransmission described in the literature may not be relevant to the therapeutic action of fluoxetine(3)."

Fluoxetine and Citalopram (Celexa):
"No compound modified dialysate dopamine in the nucleus accumbens(4)."

Sertraline (Zoloft) and desipramine(not an SSRI):
"Fifth, contribution of noradrenaline and serotonin to the observed effects seems unlikely since specific reuptake blockers (desipramine and sertraline, respectively) did not alter them(5)."

Bupropion (Wellbutrin):
"In vivo brain microdialysis studies demonstrate that, after chronic administration, there is an enhancement of bupropion-induced increases in extracellular dopamine in the nucleus accumbens(6)."

"Bupropion decreased DOPAC concentrations, increased 5-HIAA, and had variable effects on homovanillic acid (HVA) (decreases with 10 mg/kg and increases with 25 and 100 mg/kg). The increase in extracellular DA after bupropion (25 mg/kg) was blocked by tetrodotoxin and was therefore action potential-dependent. Bupropion produced similar neurochemical reponses in the striatum and the nucleus accumbens. These results suggest that increases in DA transmission contribute to the behavioral effects of bupropion and are consistent with a role for DA in the antidepressant effects of this drug(7)."

-That would seem to signal that Wellbutrin has effects on serotonin (I'm sure it does, although the effects are weak). I'm not exactly sure about what implications that finding holds, however.

This discussion seems to hold some interesting consequences as far as antidepressant efficacy is concerned.

Shawn

(1)
http://www4.infotrieve.com/newmedline/detail.asp?NameID=11723184&loggedusing=M&Session=102188&SearchQuery=%22SB+216641%22&count=9
(2)
http://www4.infotrieve.com/newmedline/detail.asp?NameID=11841572&loggedusing=M&Session=102188&SearchQuery=gaba+and+VTA+and+dopamine+and+accumbens&count=41
(3)
http://www4.infotrieve.com/search/databases/detailsNew.asp?artID=29798457
(4)
http://www4.infotrieve.com/search/databases/detailsNew.asp?artID=26503862
(5)
http://www4.infotrieve.com/search/databases/detailsNew.asp?artID=18595323
-I should mention that it's actually glutamate neurons that cause dopamine release in the nucleus accumbens; GABA inhibits them.
(6)
http://www4.infotrieve.com/search/databases/detailsNew.asp?artID=7180340
(7)
http://www4.infotrieve.com/search/databases/detailsNew.asp?artID=20353605


>
> so if you block the uptake of 5HT you increase the level of dopamine in the nucleus accumbens, ... whereas if you enhance the uptake of 5HT you increase the level of dopamine in the nucleus accumbens...
>
> any information on this mechanism Shawn ?


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poster:Shawn. T. thread:114758
URL: http://www.dr-bob.org/babble/20020731/msgs/114885.html