Psycho-Babble Neurotransmitters Thread 883495

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Re: Do SSRI's cause dopamine depletion

Posted by Alexanderfromdenmark on March 6, 2009, at 10:38:05

In reply to Do SSRI's cause dopamine depletion, posted by Alexanderfromdenmark on March 3, 2009, at 10:46:37

I must say this concerns me a bit

"Chronic treatment with fluoxetine (Prozac) has been shown to cause persistent desensitization of 5HT1A receptors even after removal of the SSRI in rats.[25] These long-term adaptive changes in 5-HT receptors, as well as more complex, global changes, are likely to be mediated through alterations of gene expression.[26][27][28][29][30] Some of these gene expression changes are a result of altered DNA structure caused by chromatin remodeling,[31][32] specifically epigenetic modification of histones[33] and gene silencing by DNA methylation due to increased expression of the methyl binding proteins MeCP2 and MBD1.[34] Altered gene expression and chromatin remodeling are also involved in the mechanism of action of electroconvulsive therapy (ECT).[35][36]
Because described gene expression changes are complex, and can involve persistent modifications of chromatin structure, it has been suggested that SSRI use can result in persistently altered cerebral gene expression leading to compromised catecholaminergic neurotransmission and neuroendocrine disturbances,[11] such as decreased testosterone levels[37], reduced sperm counts[38], and reduced semen quality with damaged sperm DNA[39]. However, without detailed neuropsychopharmacological, pharmacogenomic and toxicogenomic[40] research, the definitive cause remains unknown."

 

Re: Do SSRI's cause dopamine depletion » Alexanderfromdenmark

Posted by Phillipa on March 7, 2009, at 12:55:48

In reply to Re: Do SSRI's cause dopamine depletion, posted by Alexanderfromdenmark on March 6, 2009, at 10:38:05

So we should go off all ad's? Phillipa

 

Re: Do SSRI's cause dopamine depletion » Phillipa

Posted by Alexanderfromdenmark on March 8, 2009, at 5:49:25

In reply to Re: Do SSRI's cause dopamine depletion » Alexanderfromdenmark, posted by Phillipa on March 7, 2009, at 12:55:48

> So we should go off all ad's? Phillipa

No, of course not if they help

 

Re: Do SSRI's cause dopamine depletion » Alexanderfromdenmark

Posted by Phillipa on March 8, 2009, at 19:34:49

In reply to Re: Do SSRI's cause dopamine depletion » Phillipa, posted by Alexanderfromdenmark on March 8, 2009, at 5:49:25

They don't. Phillipa

 

Re: Do SSRI's cause dopamine depletion

Posted by Alexanderfromdenmark on March 9, 2009, at 9:25:59

In reply to Re: Do SSRI's cause dopamine depletion » Alexanderfromdenmark, posted by Phillipa on March 8, 2009, at 19:34:49

> They don't. Phillipa

Then what's the point of being on them? This isn't topic about bashing SSRIs, it's just about trying to understand, how they work and how they affect the brain long-term, but if they aren't benefitting you, I don't see any reason not to go off them or switching med strategy.

 

Re: Do SSRI's cause dopamine depletion » Alexanderfromdenmark

Posted by sowhysosad on April 5, 2009, at 16:39:40

In reply to Re: Do SSRI's cause dopamine depletion, posted by Alexanderfromdenmark on March 9, 2009, at 9:25:59

SSRI's also render D2 dopamine receptors supersensitive, which they think might contribute to the antidepressant effect.

That said, so does CBT alone according to some other research, so maybe it's some healing mechanism of the brain as it recovers from depression.

 

Re: Do SSRI's cause dopamine depletion

Posted by Alexanderfromdenmark on April 6, 2009, at 3:06:33

In reply to Re: Do SSRI's cause dopamine depletion » Alexanderfromdenmark, posted by sowhysosad on April 5, 2009, at 16:39:40

> SSRI's also render D2 dopamine receptors supersensitive, which they think might contribute to the antidepressant effect.
>
> That said, so does CBT alone according to some other research, so maybe it's some healing mechanism of the brain as it recovers from depression.


Perhaps, depends on the SSRI of course. A drug like prozac has actually been shown to an "atypical" antidepressant in that it also inhibits reuptake of noradrenalin and dopamine.

My own experience with lexapro has been quite catastropic in that it just numbed me up, made me fatigued and apathectic, and has caused me secondary hypogonadism and lowered my thyroid hormone t3. Antidepressant my *ss.

 

Re: Do SSRI's cause dopamine depletion

Posted by sowhysosad on April 6, 2009, at 15:08:47

In reply to Re: Do SSRI's cause dopamine depletion, posted by Alexanderfromdenmark on April 6, 2009, at 3:06:33

> > SSRI's also render D2 dopamine receptors supersensitive, which they think might contribute to the antidepressant effect.
> >
> > That said, so does CBT alone according to some other research, so maybe it's some healing mechanism of the brain as it recovers from depression.
>
>
> Perhaps, depends on the SSRI of course. A drug like prozac has actually been shown to an "atypical" antidepressant in that it also inhibits reuptake of noradrenalin and dopamine.
>
> My own experience with lexapro has been quite catastropic in that it just numbed me up, made me fatigued and apathectic, and has caused me secondary hypogonadism and lowered my thyroid hormone t3. Antidepressant my *ss.
>

Pretty much all the SSRI's sensitise D2 receptors from what I've read, or at least fluoxetine, citalopram and paroxetine do:

http://www.ncbi.nlm.nih.gov/pubmed/15820269

As for fluoxetine and noradrenaline/dopamine, you're right in saying it increases levels of those neurotransmitters, at least in the prefrontal cortex. However, it doesn't significantly inhibit reuptake of catecholamines, so it must be doing it through some other mechanism.

 

Re: Do SSRI's cause dopamine depletion

Posted by Alexanderfromdenmark on April 8, 2009, at 17:28:11

In reply to Re: Do SSRI's cause dopamine depletion, posted by sowhysosad on April 6, 2009, at 15:08:47

> > > SSRI's also render D2 dopamine receptors supersensitive, which they think might contribute to the antidepressant effect.
> > >
> > > That said, so does CBT alone according to some other research, so maybe it's some healing mechanism of the brain as it recovers from depression.
> >
> >
> > Perhaps, depends on the SSRI of course. A drug like prozac has actually been shown to an "atypical" antidepressant in that it also inhibits reuptake of noradrenalin and dopamine.
> >
> > My own experience with lexapro has been quite catastropic in that it just numbed me up, made me fatigued and apathectic, and has caused me secondary hypogonadism and lowered my thyroid hormone t3. Antidepressant my *ss.
> >
>
> Pretty much all the SSRI's sensitise D2 receptors from what I've read, or at least fluoxetine, citalopram and paroxetine do:
>
> http://www.ncbi.nlm.nih.gov/pubmed/15820269
>
> As for fluoxetine and noradrenaline/dopamine, you're right in saying it increases levels of those neurotransmitters, at least in the prefrontal cortex. However, it doesn't significantly inhibit reuptake of catecholamines, so it must be doing it through some other mechanism.

But what is the significance of sensitizing d2 receptors? Generally I seem to find that studies show that ssri's downregulate dopamine, as such there is less dopamine and not more, sensitizing d2 receptors ot not.

on the subject on dopamine depletion take a look at this.

http://ajp.psychiatryonline.org/cgi/content/full/162/9/1755

 

Re: Do SSRI's cause dopamine depletion

Posted by sowhysosad on April 8, 2009, at 21:36:35

In reply to Re: Do SSRI's cause dopamine depletion, posted by Alexanderfromdenmark on April 8, 2009, at 17:28:11

> But what is the significance of sensitizing d2 receptors? Generally I seem to find that studies show that ssri's downregulate dopamine, as such there is less dopamine and not more, sensitizing d2 receptors ot not.
>
> on the subject on dopamine depletion take a look at this.
>
> http://ajp.psychiatryonline.org/cgi/content/full/162/9/1755

I'm not entirely sure what the significance is Alexander and the research is quite vague, just speculating that it "contributes to the antidepressant effect" in some way. I'd imagine it makes the brain more sensitive to the effects of what dopamine remains, and thus helps with energy, concentration and sleep regulation.

Interesting article about dopamine depletion. I've suffered some of those symptoms recently, which lends weight to my theory that my dopamine levels are low.

 

Re: Do SSRI's cause dopamine depletion

Posted by Amelia_in_StPaul on April 20, 2009, at 17:03:12

In reply to Re: Do SSRI's cause dopamine depletion » Alexanderfromdenmark, posted by sowhysosad on April 5, 2009, at 16:39:40

Not all of the SSRIs do the same thing. Fluoxetine has a different effect on dopamine than other SSRIs.

Fluoxetine as monotherapy in psychotic depression:
Report of 4 cases

(Excerpt) Recent studies demonstrate that serotonin exhibits a regulatory dopaminergic action by inhibiting the release of dopamine through 5-HT2A somatodendritic receptors in the surface of dopaminergic neurons; thus 5-HT2A antagonists (Altanserin) and 5-HT1A agonists (which may exert subtle inhibitory effects on dopaminergic cell bodies in the substantia nigra by means of autoreceptors ; Kelland, M.D. et al., 1990) or injury to the serotonergic tracts (Dray, A. et al., 1978), produce a disinhibition of dopaminergic neurons in the middle brain with modest increases in the release (Ennis, C. et al.,1981) and possibly in the synthesis of dopamine (Spampinato, U. et al., 1985) in the nucleus accumbens and the prefrontal cortex (Waldmeier, P.C. & Delini-Stula, A.A., 1979; Nedergaard, S. et al., 1988; Kelland, M.D. et al., 1990; Leysen, J.E. et al., 1994). On the other hand, some of the effects of the serotonin in the dopaminergic system can be mediated in indirect form through the modulation of the GABA and the cholinergic system (Dewey, S.L. et al., 1993). Fluoxetine and its active metabolite, norfluoxetine, have a serotonergic profile inhibiting serotonin reuptake the synaptic cleft (Lucas, R.A., 1992). However, the effect of the fluoxetine on other monoaminergic systems is not clearly established. Fluoxetine has been associated with the development of bradykinesia and rigidity, akathisia, shuffling gait, cogwheeling, tremor and akathisia, possibly by the activation of 5-HT2a receptors in dopaminergic neurons (Bouchard, R.H. et al., 1989; Lipinski, J.F. Jr. et al., 1989; Arya, D.K., 1994; Coulter, D.M. & Pillans, P.I., 1995) in a proportion similar to 1 out of 1000 individuals that consume SSRIs (Choo, V ., 1993). Fluoxetine, by increasing the serotonergic activity in the projections toward the substantia nigra from the dorsal raphe nuclei, can inhibit the firing rate of dopaminergic neurons, in such a way that the dopamine blockers in combination with fluoxetine can lead to extrapyramidal effects in patients even when they havent experienced adverse effects when treated only with antipsychotics (Levinson, M.L. et al., 1991). In spite of such findings, fluoxetine has relatively few side effects, especially when compared with the tricyclic antidepressants (Cooper, G.L., 1988) or with Amoxapine (Anton, R.F. & Burch, E.A., 1990).

Effects of fluoxetine on dopamine D2 receptors in the human brain: a positron emission tomography study

We have previously reported that repeated dosing with the selective serotonin reuptake inhibitor (SSRI) citalopram decreases striatal [11C]raclopride binding in healthy volunteers. As the SSRI-class antidepressant drugs are believed to have a similar mechanism of action, we wanted to explore whether the prototype SSRI drug, fluoxetine, shares the effects of citalopram on subcortical dopamine neurotransmission. Eight healthy male volunteers were studied using a randomized double-blind placebo-controlled study design. Striatal and thalamic D2-receptor binding was measured at baseline, after a single oral dose (20 mg) of fluoxetine, and after repeated dosing (2 wk, 20 mg/d). The D2-receptor binding potential (BP) was assessed using [11C]raclopride and 3D positron emission tomography. Repeated dosing of fluoxetine decreased BP in the right medial thalamus (p=0.022). Fluoxetine did not decrease striatal BP, but there was a trend (p=0.090) towards increased BP in the left putamen after repeated dosing. A single dose of fluoxetine did not affect BP in the thalamus or striatum. Fluoxetine appears to have a regionally selective effect on the dopaminergic neurotransmission in various areas of the brain. The current results after fluoxetine together with our previous data on citalopram suggest that the modulatory effects of these drugs on striatal dopaminergic neurotransmission are different upon repeated dosing and further substantiates pharmacological differences between SSRI-class drugs.

 

Re: Do SSRI's cause dopamine depletion

Posted by sowhysosad on April 21, 2009, at 7:08:07

In reply to Re: Do SSRI's cause dopamine depletion, posted by Amelia_in_StPaul on April 20, 2009, at 17:03:12

> Not all of the SSRIs do the same thing. Fluoxetine has a different effect on dopamine than other SSRIs.

...which would explain why many people find they're more motivated and energetic on fluoxetine than with other SSRI's ("activating" in the marketing spiel), and why it seems to work pretty well for atypical depression.

 

Re: Do SSRI's cause dopamine depletion

Posted by sowhysosad on April 21, 2009, at 7:26:14

In reply to Re: Do SSRI's cause dopamine depletion, posted by sowhysosad on April 21, 2009, at 7:08:07

Due to sleep deprivation and general stupidity I just posted without even reading the research, thinking it was this old chestnut:

Résumé / Abstract
Rationale: The selective serotonin uptake inhibitor (SSRI) fluoxetine has been shown to not only increase the extracellular concentrations of serotonin, but also dopamine and norepinephrine extracellular concentrations in rat prefrontal cortex. The effect of other SSRIs on monoamine concentrations in prefrontal cortex has not been thoroughly studied. Objective: The aim of this study was to compare the ability of five systemically administered selective serotonin uptake inhibitors to increase acutely the extracellular concentrations of serotonin, norepinephrine and dopamine in rat prefrontal cortex. Methods: The extracellular concentrations of monoamines were determined in the prefrontal cortex of conscious rats using the microdialysis technique. Results: Fluoxetine, citalopram, fluvoxamine, paroxetine and sertraline similarly increased the extracellular concentrations of serotonin from 2- to 4-fold above baseline. However, only fluoxetine produced robust and sustained increases in extracellular concentrations of norepinephrine and dopamine after acute systemic administration. Fluoxetine at the same dose blocked ex vivo binding to the serotonin transporter, but not the norepinephrine transporter, suggesting that the increase of catecholamines was not due to non-selective blockade of norepinephrine uptake. Prefrontal cortex extracellular concentrations of fluoxetine at the dose that increased extracellular monoamines were 242 nM, a concentration sufficient to block 5-HT2C receptors which is a potential mechanism for the fluoxetine-induced increase in catecholamines. Conclusion: Amongst the SSRIs examined, only fluoxetine acutely increases extracellular concentrations of norepinephrine and dopamine as well as serotonin in prefrontal cortex, suggesting that fluoxetine is an atypical SSRI.

I'm far too tired to get my head around that second piece of research that Amelia posted - is it contradicting other studies which say SSRI's reduce D2 receptor availability? Does the reduced binding potential mean the fluoxetine is acting as a D2 antagonist? I've also previously read that SSRI's supersensitise D2 receptors. My brain hurts...

 

Re: Do SSRI's cause dopamine depletion

Posted by Alexanderfromdenmark on April 26, 2009, at 17:43:58

In reply to Re: Do SSRI's cause dopamine depletion, posted by sowhysosad on April 21, 2009, at 7:26:14

> Due to sleep deprivation and general stupidity I just posted without even reading the research, thinking it was this old chestnut:
>
> Résumé / Abstract
> Rationale: The selective serotonin uptake inhibitor (SSRI) fluoxetine has been shown to not only increase the extracellular concentrations of serotonin, but also dopamine and norepinephrine extracellular concentrations in rat prefrontal cortex. The effect of other SSRIs on monoamine concentrations in prefrontal cortex has not been thoroughly studied. Objective: The aim of this study was to compare the ability of five systemically administered selective serotonin uptake inhibitors to increase acutely the extracellular concentrations of serotonin, norepinephrine and dopamine in rat prefrontal cortex. Methods: The extracellular concentrations of monoamines were determined in the prefrontal cortex of conscious rats using the microdialysis technique. Results: Fluoxetine, citalopram, fluvoxamine, paroxetine and sertraline similarly increased the extracellular concentrations of serotonin from 2- to 4-fold above baseline. However, only fluoxetine produced robust and sustained increases in extracellular concentrations of norepinephrine and dopamine after acute systemic administration. Fluoxetine at the same dose blocked ex vivo binding to the serotonin transporter, but not the norepinephrine transporter, suggesting that the increase of catecholamines was not due to non-selective blockade of norepinephrine uptake. Prefrontal cortex extracellular concentrations of fluoxetine at the dose that increased extracellular monoamines were 242 nM, a concentration sufficient to block 5-HT2C receptors which is a potential mechanism for the fluoxetine-induced increase in catecholamines. Conclusion: Amongst the SSRIs examined, only fluoxetine acutely increases extracellular concentrations of norepinephrine and dopamine as well as serotonin in prefrontal cortex, suggesting that fluoxetine is an atypical SSRI.
>
> I'm far too tired to get my head around that second piece of research that Amelia posted - is it contradicting other studies which say SSRI's reduce D2 receptor availability? Does the reduced binding potential mean the fluoxetine is acting as a D2 antagonist? I've also previously read that SSRI's supersensitise D2 receptors. My brain hurts...

I think all this far too complicated for us depressed brain foggers. Fx, the insomnia caused by the SSRI's could cause increased dopamine in the following day, because the brain is compensating for the lack of sleep. However I do feel that most SSRI side effects and things like hyperprolactima are definite pointers toward inhibition of dopamine.

 

Re: Do SSRI's cause dopamine depletion

Posted by Alexanderfromdenmark on April 26, 2009, at 17:48:50

In reply to Re: Do SSRI's cause dopamine depletion, posted by Alexanderfromdenmark on April 26, 2009, at 17:43:58

Also I think there's a difference between acute admnistration and long term adminitstration. Fx the brain in reponse to the huge increase in serotonin made say "F*ck man, lets pump out some dopamine to balance things out", so you get an increase dopamine, then you take an SSRI again and the brain again says "F*ck it man, keep that dopamine going, pump it up!", then after a period of weeks or months "The adujustment period", the brain just says"f*ck it, no more, we'll just get used to all that f*ck*ng serotonin and stop pumpting the dopamine" and that's when stuff like SSRI apathy, fatigue and PSSD complications set in.

 

Re: Do SSRI's cause dopamine depletion » Alexanderfromdenmark

Posted by sowhysosad on April 26, 2009, at 22:30:20

In reply to Re: Do SSRI's cause dopamine depletion, posted by Alexanderfromdenmark on April 26, 2009, at 17:48:50

> Also I think there's a difference between acute admnistration and long term adminitstration. Fx the brain in reponse to the huge increase in serotonin made say "F*ck man, lets pump out some dopamine to balance things out", so you get an increase dopamine, then you take an SSRI again and the brain again says "F*ck it man, keep that dopamine going, pump it up!", then after a period of weeks or months "The adujustment period", the brain just says"f*ck it, no more, we'll just get used to all that f*ck*ng serotonin and stop pumpting the dopamine" and that's when stuff like SSRI apathy, fatigue and PSSD complications set in.

You could be right. Weirdly though, SSRI's can also increase dopamine through other mechanisms. As I understand it, the dopamine reuptake pump starts to soak up some of that excess serotonin floating around, thus preventing reuptake of dopamine and leaving more in the synapse. Maybe that's how fluoxetine boosts dopamine in some parts of the brain?

After 3+ years on escitalopram followed by a lovely bout of sertraline-induced akathisia, it feels like I've been in a hypodopaminergic state for like 8 months now. All the symptoms seem to bear this out. Other AD's I've taken in the meantime seem to have somehow made it worse. As I mentioned elsewhere, NADH seems to be reversing the effect, thank f***.

 

Re: Do SSRI's cause dopamine depletion to d/r

Posted by Meltingpot on May 17, 2009, at 10:25:42

In reply to Re: Do SSRI's cause dopamine depletion, posted by desolationrower on March 4, 2009, at 20:54:14

Hi,

I thought wellbutrin acted more on norepinephrine thant on dopamine??

Denise

 

Re: Do SSRI's cause dopamine depletion to d/r

Posted by Alexanderfromdenmark on May 17, 2009, at 10:41:41

In reply to Re: Do SSRI's cause dopamine depletion to d/r, posted by Meltingpot on May 17, 2009, at 10:25:42

> Hi,
>
> I thought wellbutrin acted more on norepinephrine thant on dopamine??
>
> Denise


I think there are some conflicting views on that. Some sources say that wellbutrin equally inhibits NA and DA uptake, and some say it inhibits NA more than DA, and some DA more than NA. You might be right though. Why do you ask?

 

Re: Do SSRI's cause dopamine depletion to d/r

Posted by Meltingpot on May 17, 2009, at 11:19:12

In reply to Re: Do SSRI's cause dopamine depletion to d/r, posted by Alexanderfromdenmark on May 17, 2009, at 10:41:41

Hi,

That was a quick response :-) I ask because I tried Wellbutrin 350mg for two weeks and I felt nothing on it. I was thinking/hoping that perhaps this is because it does not act on dopamine so much as norepinephrine.

The reason I hoped this was the case was because at some point I would like to try a dopamine agonist but if Wellbutrin does act strongly on dopamine then this would increase my chances of not responding to a dopamine agonist.

Denise

 

Re: Do SSRI's cause dopamine depletion to d/r

Posted by Alexanderfromdenmark on May 17, 2009, at 11:39:47

In reply to Re: Do SSRI's cause dopamine depletion to d/r, posted by Meltingpot on May 17, 2009, at 11:19:12

> Hi,
>
> That was a quick response :-) I ask because I tried Wellbutrin 350mg for two weeks and I felt nothing on it. I was thinking/hoping that perhaps this is because it does not act on dopamine so much as norepinephrine.
>
> The reason I hoped this was the case was because at some point I would like to try a dopamine agonist but if Wellbutrin does act strongly on dopamine then this would increase my chances of not responding to a dopamine agonist.
>
> Denise


I don't think you should use Wellbutrin as your reference for a dopamine agonist. There's a lot of other definitive dopamine drugs out there.

 

Re: Do SSRI's cause dopamine depletion to d/r

Posted by garnet71 on May 17, 2009, at 16:32:03

In reply to Re: Do SSRI's cause dopamine depletion to d/r, posted by Meltingpot on May 17, 2009, at 11:19:12

The last time I tried Wellbutrin, it did not work at all for me; a few weeks later, I started taking dextro-amp which works much of the time....though I can't see it as a long term solution..However, I don't think Wellbutrin is comparable to other psychotropics-at least none I know of...

450 mg of WB worked best for me in the past....

Don't give up :-)

 

Re: Do SSRI's cause dopamine depletion » sowhysosad

Posted by Amelia_in_StPaul on May 18, 2009, at 23:30:16

In reply to Re: Do SSRI's cause dopamine depletion » Alexanderfromdenmark, posted by sowhysosad on April 26, 2009, at 22:30:20

I have cited studies that conclude exactly that (and specifically in regards to fluoxetine). Maybe in this thread? Anyway, yes, I believe that's what happens.

>, As I understand it, the dopamine reuptake pump starts to soak up some of that excess serotonin floating around, thus preventing reuptake of dopamine and leaving more in the synapse. Maybe that's how fluoxetine boosts dopamine in some parts of the brain?
>

 

Re: Do SSRI's cause dopamine depletion

Posted by desolationrower on May 19, 2009, at 0:44:55

In reply to Re: Do SSRI's cause dopamine depletion » sowhysosad, posted by Amelia_in_StPaul on May 18, 2009, at 23:30:16

yeah, studies different NA/DA effect of wellbutrin. and it might be an na releaser. or wrok by tnf-alpha inhibition. i don't think you can say its the same as pramiprexole or d-amp or desipramine.

-d/r

 

Re: Do SSRI's cause dopamine depletion » sowhysosad

Posted by SLS on May 20, 2009, at 5:44:34

In reply to Re: Do SSRI's cause dopamine depletion » Alexanderfromdenmark, posted by sowhysosad on April 26, 2009, at 22:30:20

> > Also I think there's a difference between acute admnistration and long term adminitstration. Fx the brain in reponse to the huge increase in serotonin made say "F*ck man, lets pump out some dopamine to balance things out", so you get an increase dopamine, then you take an SSRI again and the brain again says "F*ck it man, keep that dopamine going, pump it up!", then after a period of weeks or months "The adujustment period", the brain just says"f*ck it, no more, we'll just get used to all that f*ck*ng serotonin and stop pumpting the dopamine" and that's when stuff like SSRI apathy, fatigue and PSSD complications set in.
>
> You could be right. Weirdly though, SSRI's can also increase dopamine through other mechanisms. As I understand it, the dopamine reuptake pump starts to soak up some of that excess serotonin floating around, thus preventing reuptake of dopamine and leaving more in the synapse. Maybe that's how fluoxetine boosts dopamine in some parts of the brain?


Don't forget circuitry.

I think it has more to do with serotoninergic pathways modulating dopaminergic neurotransmission downstream. Perhaps there is a dysinhibition of dopamine activity as specific 5-HT receptors downregulate as a result of chronic exposure to SRI drugs like fluoxetine. Fluoxetine is a strange drug that is often considered to be an atypical SSRI. It does more than just inhibit the reuptake of serotonin.


- Scott


*********************************************

Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex
by
Bymaster FP, Zhang W, Carter PA,
Shaw J, Chernet E, Phebus L, Wong DT, Perry KW.
Neuroscience Research Division,
Lilly Research Laboratories,
Lilly Corporate Center, Indianapolis, IN 46285-0510, USA.
[email protected]
Psychopharmacology (Berl) 2002 Apr;160(4):353-61

ABSTRACT

RATIONALE: The selective serotonin uptake inhibitor (SSRI) fluoxetine has been shown to not only increase the extracellular concentrations of serotonin, but also dopamine and norepinephrine extracellular concentrations in rat prefrontal cortex. The effect of other SSRIs on monoamine concentrations in prefrontal cortex has not been thoroughly studied. OBJECTIVE: The aim of this study was to compare the ability of five systemically administered selective serotonin uptake inhibitors to increase acutely the extracellular concentrations of serotonin, norepinephrine and dopamine in rat prefrontal cortex. METHODS: The extracellular concentrations of monoamines were determined in the prefrontal cortex of conscious rats using the microdialysis technique. RESULTS: Fluoxetine, citalopram, fluvoxamine, paroxetine and sertraline similarly increased the extracellular concentrations of serotonin from 2- to 4-fold above baseline. However, only fluoxetine produced robust and sustained increases in extracellular concentrations of norepinephrine and dopamine after acute systemic administration. Fluoxetine at the same dose blocked ex vivo binding to the serotonin transporter, but not the norepinephrine transporter, suggesting that the increase of catecholamines was not due to non-selective blockade of norepinephrine uptake. Prefrontal cortex extracellular concentrations of fluoxetine at the dose that increased extracellular monoamines were 242 nM, a concentration sufficient to block 5-HT(2C) receptors which is a potential mechanism for the fluoxetine-induced increase in catecholamines. CONCLUSION: Amongst the SSRIs examined, only fluoxetine acutely increases extracellular concentrations of norepinephrine and dopamine as well as serotonin in prefrontal cortex, suggesting that fluoxetine is an atypical SSRI.

 

Re: Do SSRI's cause dopamine depletion » sowhysosad

Posted by SLS on May 20, 2009, at 5:46:21

In reply to Re: Do SSRI's cause dopamine depletion » Alexanderfromdenmark, posted by sowhysosad on April 26, 2009, at 22:30:20

> > Also I think there's a difference between acute admnistration and long term adminitstration. Fx the brain in reponse to the huge increase in serotonin made say "F*ck man, lets pump out some dopamine to balance things out", so you get an increase dopamine, then you take an SSRI again and the brain again says "F*ck it man, keep that dopamine going, pump it up!", then after a period of weeks or months "The adujustment period", the brain just says"f*ck it, no more, we'll just get used to all that f*ck*ng serotonin and stop pumpting the dopamine" and that's when stuff like SSRI apathy, fatigue and PSSD complications set in.
>
> You could be right. Weirdly though, SSRI's can also increase dopamine through other mechanisms. As I understand it, the dopamine reuptake pump starts to soak up some of that excess serotonin floating around, thus preventing reuptake of dopamine and leaving more in the synapse. Maybe that's how fluoxetine boosts dopamine in some parts of the brain?


Don't forget circuitry.

I think it has more to do with serotoninergic pathways modulating dopaminergic neurotransmission downstream. Perhaps there is a dysinhibition of dopamine activity as specific 5-HT receptors downregulate as a result of chronic exposure to SRI drugs like fluoxetine. Fluoxetine is a strange drug that is often considered to be an atypical SSRI. It does more than just inhibit the reuptake of serotonin.


- Scott


*********************************************

Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex
by
Bymaster FP, Zhang W, Carter PA,
Shaw J, Chernet E, Phebus L, Wong DT, Perry KW.
Neuroscience Research Division,
Lilly Research Laboratories,
Lilly Corporate Center, Indianapolis, IN 46285-0510, USA.
[email protected]
Psychopharmacology (Berl) 2002 Apr;160(4):353-61

ABSTRACT

RATIONALE: The selective serotonin uptake inhibitor (SSRI) fluoxetine has been shown to not only increase the extracellular concentrations of serotonin, but also dopamine and norepinephrine extracellular concentrations in rat prefrontal cortex. The effect of other SSRIs on monoamine concentrations in prefrontal cortex has not been thoroughly studied. OBJECTIVE: The aim of this study was to compare the ability of five systemically administered selective serotonin uptake inhibitors to increase acutely the extracellular concentrations of serotonin, norepinephrine and dopamine in rat prefrontal cortex. METHODS: The extracellular concentrations of monoamines were determined in the prefrontal cortex of conscious rats using the microdialysis technique. RESULTS: Fluoxetine, citalopram, fluvoxamine, paroxetine and sertraline similarly increased the extracellular concentrations of serotonin from 2- to 4-fold above baseline. However, only fluoxetine produced robust and sustained increases in extracellular concentrations of norepinephrine and dopamine after acute systemic administration. Fluoxetine at the same dose blocked ex vivo binding to the serotonin transporter, but not the norepinephrine transporter, suggesting that the increase of catecholamines was not due to non-selective blockade of norepinephrine uptake. Prefrontal cortex extracellular concentrations of fluoxetine at the dose that increased extracellular monoamines were 242 nM, a concentration sufficient to block 5-HT(2C) receptors which is a potential mechanism for the fluoxetine-induced increase in catecholamines. CONCLUSION: Amongst the SSRIs examined, only fluoxetine acutely increases extracellular concentrations of norepinephrine and dopamine as well as serotonin in prefrontal cortex, suggesting that fluoxetine is an atypical SSRI.


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Psycho-Babble Neurotransmitters | Extras | FAQ


[dr. bob] Dr. Bob is Robert Hsiung, MD, [email protected]

Script revised: February 4, 2008
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