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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 10 to 34 of 34. Go back in thread:
Posted by bleauberry on April 9, 2009, at 16:11:00
In reply to Dopamine depletion: A myth?, posted by SLS on April 9, 2009, at 8:10:25
I don't know if I could find it again, but one day surfing on pubmed I came across a study on rats where they showed that longterm ssri's caused the excess serotonin to be taken up by dopamine neurons. Theoretically an effort by genetic coding to deal with the artificially increased serotonin. If that is true, it would go a long way to explain poopout and ssri apathy syndrome. Serotonin getting involved in the dopamine circuits could do weird things like that, I imagine.
There must be some crosstalk between circuits. For example, Stahl wrote that Milnacipran will increase dopamine in the frontal cortex by blocking NE reuptake, because dopamine reuptake sites in the frontal cortex are lacking and the dopamine is normally taken up into the NE sites in that area.
I'm not sure about the dopamine depletion theory. I think serotonin taking a ride through the dopamine circuits where it doesn't belong makes more sense.
Posted by garnet71 on April 9, 2009, at 18:39:14
In reply to Re: Dopamine depletion: A myth?, posted by desolationrower on April 9, 2009, at 14:33:04
"i mean it combines a goofy 'theory' with the idea that you can 'feel' the effect of a neurotransmitter"
Hey crabby, er..genious, uh antibrotelligence..
not everyone can stay up all night AND read medical journals
and
not everyone can stay up all night OR read medical journals
Personally, I LIKE talking about "goofy" theories and "feeling" neurotransmitters that I can't even spell or pronounce. So - quit trying to ruin it for us all!
Posted by myco on April 9, 2009, at 18:47:38
In reply to Re: Dopamine depletion: A myth? » desolationrower, posted by garnet71 on April 9, 2009, at 18:39:14
ooo there you go again with the logic....youre just gettin me all ex-thhhited ova'ere
*tickles ya bum*
:oP
----------
> "i mean it combines a goofy 'theory' with the idea that you can 'feel' the effect of a neurotransmitter"
>
> Hey crabby, er..genious, uh antibrotelligence..
>
> not everyone can stay up all night AND read medical journals
>
> and
>
> not everyone can stay up all night OR read medical journals
>
> Personally, I LIKE talking about "goofy" theories and "feeling" neurotransmitters that I can't even spell or pronounce. So - quit trying to ruin it for us all!
Posted by Garnet71 on April 9, 2009, at 18:52:09
In reply to Re: Dopamine depletion: A myth? » garnet71, posted by myco on April 9, 2009, at 18:47:38
Myco, seriously...
I WOULD KICK YOUR *SS
if you ever tried anything like that
Posted by myco on April 9, 2009, at 19:00:59
In reply to Re: Dopamine depletion: A myth? » myco, posted by Garnet71 on April 9, 2009, at 18:52:09
LOL ahhh.. trouble seeing through jokes huh hun. s'ok, we all have our days...you dont know me hun...dont judge :o)
> Myco, seriously...
>
> I WOULD KICK YOUR *SS
>
> if you ever tried anything like that
Posted by Garnet71 on April 9, 2009, at 20:09:25
In reply to Re: Dopamine depletion: A myth? » Garnet71, posted by myco on April 9, 2009, at 19:00:59
Myco, not judging...just my initial reaction. I'm not mad at you.
Don't worry about it...No hard feelings, ok?
:)
Posted by myco on April 9, 2009, at 20:50:30
In reply to Re: Dopamine depletion: A myth?, posted by Garnet71 on April 9, 2009, at 20:09:25
of course not... just know i'm not a bad guy ok.
*hugs
> Myco, not judging...just my initial reaction. I'm not mad at you.
>
> Don't worry about it...No hard feelings, ok?
>
> :)
Posted by Phillipa on April 9, 2009, at 21:25:35
In reply to Re: Dopamine depletion: A myth? » Garnet71, posted by myco on April 9, 2009, at 20:50:30
Myco well doesn't everyone know that already? Greatest person I know. Love Phillipa
Posted by yxibow on April 10, 2009, at 2:14:59
In reply to Dopamine depletion: A myth?, posted by SLS on April 9, 2009, at 8:10:25
> Yes, I have heard for years that SSRIs cause dopamine depletion, and that this might be responsible for the induction of apathy/amotivation/anhedonia or a loss of therapeutic effect ("poop-out"). However, where is there scientific evidence to support this notion? I would say that chronic SSRI usage might produce a change in the activity of neural pathways afferent to dopaminergic structures and circuits. However, to think that neurons actually run out of neurotransmitter seems unlikely to me. They probably are just not being stimulated to release the dopamine that they keep in storage.
>
> What do you think? Is there any scientific evidence that demonstrates that an SSRI can produce dopamine depletion downstream?
>
>
> - Scott
>
I'm not sure about long term effects but I know, at least by evidence based psychiatry that a large dose of Luvox appeared to 'downregulate' dopamine. To this day with my orphan disorder the source of D2 accentuation is unknown, but before I started on Seroquel I did try a test with high dose Luvox. It helped a bit with the bright lights and the milieu of other symptoms.(See Luvox posting)
So if that's an example of depleting in the present sense, then I guess that fits in that picture.
There is one exception to current SSRIs -- Zoloft actually has a very minor action at D2, possibly blockading like an AP, but its unclear.
-- Jay
Posted by myco on April 10, 2009, at 13:25:44
In reply to Re: Dopamine depletion: A myth?, posted by desolationrower on April 9, 2009, at 14:33:04
I can feel the effect to some extent....when I tool tyrosine and "listened" closely to my body and feelings I could feel stages coming on...from head dizzyness, enlightenment, sleepyness, then energy and irritation....pretty much in order. I am on nardil but this was evident in terms of feel. So can you argue that this is the "feel of neuros"? I dunno...but knowing the theory of what these neuros are supposed to do to you...I can actually correlate that to some extent. Those that are on so many meds...I doubt can pick out what is doing what with any real confidence....but mabye my own experience is placcbo..who knows. But something is there...its not goofy at all. Just misunderstood....isnt that in the nature of modern understanding of the brain anyway?
m
------
> well, this seems like a theory thought up by people who think they can understand the brain (i don't mean, 'idiots', i mean, overconfident and not realizing the complexity). i mean it combines a goofy 'theory' with the idea that you can 'feel' the effect of a neurotransmitter.
Posted by garnet71 on April 11, 2009, at 10:21:20
In reply to Dopamine depletion: A myth?, posted by SLS on April 9, 2009, at 8:10:25
Well here's another (non-technical) article I came across..I was looking at addiction stuff because I remember reading a similar article about low dopamine and addictions in the past that came from "addiction" studies.
http://floridadetox.com/graphics/images/AntidepressantsCanIncreaseDepressionDecreasingDopamine.pdf
Maybe there's more information in addiction research about this than we know, rather than in the neuro and pharma journals.
Posted by garnet71 on April 11, 2009, at 10:31:33
In reply to Dopamine depletion: A myth?, posted by SLS on April 9, 2009, at 8:10:25
well here's some links to some full text research, though older, the links are embedded in text on the site. I don't know if its the right stuff you are looking for or if it would help answer your question, because i generally don't read this technical stuff or need a translator. (I have no clue)
http://www.nature.com/npp/journal/v20/n5/full/1395291a.html
Functional interactions between central serotonin (5-HT) and dopamine (DA) systems have been well documented. Electrophysiological, biochemical, and behavioral evidence suggests that the ascending serotonergic pathways from the medial and dorsal raphe modulate or control the function of the mesolimbic and mesostriatal dopamine systems (Joyce 1993; Zazpe et al. 1994; Kapur and Remington 1996). The modulating effect of serotonin on striatal dopamine release is, however, controversial. For example, there is evidence that serotonin may inhibit (de Belleroche and Bradford 1980; Ennis et al. 1981; Westfall and Tittermary 1982; Blandina et al. 1988) as well as stimulate DA release in the striatum (Benloucif et al. 1993; West and Galloway 1996; De Deurwaerdere et al. 1997). Similarly, local application of 5-HT or 5-HT agonists have been shown to reduce (de Belleroche and Gardiner 1982) and facilitate dopamine efflux in the nucleus accumbens (Guan and McBride 1989; Parson and Justice 1993). In respect to the 5-HT2 receptor agonist properties of psilocybin, it is of particular note that 3,4-methylenedioxymethamphetamine (MDMA), a potent 5-HT releasing agent, has been shown to increase impulse-mediated striatal dopamine release through 5-HT2 receptor activation (Schmidt et al. 1992; Palfreyman et al. 1993; Schmidt et al. 1994; Yamamoto et al. 1995; Gudelsky and Nash 1996). Thus, 5-HT2A receptors located on dopaminergic and/or GABAergic neurons within the striatum and nucleus accumbens might provide an anatomical substrate for a serotonin-mediated psilocybin-induced dopamine release (Palacios et al. 1991).
Posted by garnet71 on April 11, 2009, at 10:42:23
In reply to Dopamine depletion: A myth?, posted by SLS on April 9, 2009, at 8:10:25
okay, one more.
http://www.mcmanweb.com/dopamine.html
it's more aggregate and contextual (my kind of article)
I'm still interested in this topic, let me know what you guys think
Posted by myco on April 11, 2009, at 11:33:47
In reply to Re: Dopamine depletion: A myth? » SLS, posted by garnet71 on April 11, 2009, at 10:21:20
I totally agree with you garnet...addiction research should play an integral role along side the biochem/physiol/psychopharm research. More angles reduce bias in thinking.
:o)
> Well here's another (non-technical) article I came across..I was looking at addiction stuff because I remember reading a similar article about low dopamine and addictions in the past that came from "addiction" studies.
>
> http://floridadetox.com/graphics/images/AntidepressantsCanIncreaseDepressionDecreasingDopamine.pdf
>
> Maybe there's more information in addiction research about this than we know, rather than in the neuro and pharma journals.
Posted by linkadge on April 12, 2009, at 7:24:27
In reply to Re: Dopamine depletion: A myth? » garnet71, posted by myco on April 11, 2009, at 11:33:47
The documentation of SSRI induced apathy is fairy comprehesnive. SSRIs are associated with increased likelyhood of developing parkinsons and sympom worsening in parkinsons disease. In animal models the SSRI's have also been linked to neuroanatomical changes to brain structures involved in movement.
Linkadge
Posted by linkadge on April 12, 2009, at 7:26:27
In reply to Re: Dopamine depletion: A myth? » garnet71, posted by myco on April 11, 2009, at 11:33:47
Some suggest the accumulation of serotonin in dopaminergic nerve terminals is part of the theraputic effect. Some suggest that it is detrimental to the theraputic effect.
Linkadge
Posted by myco on April 12, 2009, at 12:14:50
In reply to Re: Dopamine depletion: A myth?, posted by linkadge on April 12, 2009, at 7:26:27
Ya this is still controversial in the literature.
Nice to see you back Link :o)
> Some suggest the accumulation of serotonin in dopaminergic nerve terminals is part of the theraputic effect. Some suggest that it is detrimental to the theraputic effect.
>
> Linkadge
Posted by Alexanderfromdenmark on April 13, 2009, at 9:00:30
In reply to Dopamine depletion: A myth?, posted by SLS on April 9, 2009, at 8:10:25
5-htp depletes dopamine
Posted by myco on April 13, 2009, at 11:25:58
In reply to Re: Enjoy, posted by Alexanderfromdenmark on April 13, 2009, at 9:00:30
Of course it does.....the dopamine pathway and the seratonin pathway are link through other compounds....you increase on and it "uses up" more than its normal share of enzymes thus reducing the availability of that enzyme for the other pathway.
> 5-htp depletes dopamine
>
> http://www.neuroassist.com/5-HTP-depletes-dopamine.pdf
Posted by Alexanderfromdenmark on April 13, 2009, at 12:18:53
In reply to Re: Enjoy » Alexanderfromdenmark, posted by myco on April 13, 2009, at 11:25:58
> Of course it does.....the dopamine pathway and the seratonin pathway are link through other compounds....you increase on and it "uses up" more than its normal share of enzymes thus reducing the availability of that enzyme for the other pathway.
>
>
> > 5-htp depletes dopamine
> >
> > http://www.neuroassist.com/5-HTP-depletes-dopamine.pdf
>
>Well wasn't that question the point of this thread?
Posted by SLS on April 13, 2009, at 15:23:08
In reply to Re: Enjoy, posted by Alexanderfromdenmark on April 13, 2009, at 12:18:53
> > Of course it does.....the dopamine pathway and the seratonin pathway are link through other compounds....you increase on and it "uses up" more than its normal share of enzymes thus reducing the availability of that enzyme for the other pathway.
> >
> >
> > > 5-htp depletes dopamine
> > >
> > > http://www.neuroassist.com/5-HTP-depletes-dopamine.pdf
> >
> >
>
> Well wasn't that question the point of this thread?
This is a fascinating study. One must remember, though, what it is they actually looked at - synaptosomes. These are little droplets of cell membrane extracted from the brain and placed in petri dishes outside the animal (in vitro). This is not the natural environment within which neurons function (in vivo). In vitro, the entire set of synaptosomes are being bathed in a liquid containing 5-HTP and serotonin (5-HT). Serotonin will not enter a cell without having a serotonin transporter (SERT) to facilitate it. That leaves us with the possibility that serotonin is entering the synaptosome through passive transport, rather than being excluded from entry as it is in vivo.This is a study of membranes produced artificially and bathed in a synthetic medium with a substance normally not found outside the cell in vivo. What it is not, is a study of circuits.
I don't know enough to be able to comment on whether or not this study is an accurate representation of what we are looking for. Is dopamine being displaced by serotonin entering the cell, or are dopamine circuits being turned off by the overactivity of serotonin circuits?
- Scott
Posted by sowhysosad on April 13, 2009, at 17:11:17
In reply to Re: Enjoy, posted by SLS on April 13, 2009, at 15:23:08
Thanks for appraising that research in more easy-to-understand terms Scott.
Posted by desolationrower on April 14, 2009, at 2:41:01
In reply to Re: Dopamine depletion: A myth? » desolationrower, posted by garnet71 on April 9, 2009, at 18:39:14
> "i mean it combines a goofy 'theory' with the idea that you can 'feel' the effect of a neurotransmitter"
>
> Hey crabby, er..genious, uh antibrotelligence..
>
> not everyone can stay up all night AND read medical journals
>
> and
>
> not everyone can stay up all night OR read medical journals
>
> Personally, I LIKE talking about "goofy" theories and "feeling" neurotransmitters that I can't even spell or pronounce. So - quit trying to ruin it for us all!hey, i make posts sometimes about theories, but everyone is all "UM ENGLISH PLEASE!LOL!"
-d/r
Posted by metric on April 14, 2009, at 11:38:24
In reply to Dopamine depletion: A myth?, posted by SLS on April 9, 2009, at 8:10:25
> Yes, I have heard for years that SSRIs cause dopamine depletion, and that this might be responsible for the induction of apathy/amotivation/anhedonia or a loss of therapeutic effect ("poop-out"). However, where is there scientific evidence to support this notion? I would say that chronic SSRI usage might produce a change in the activity of neural pathways afferent to dopaminergic structures and circuits. However, to think that neurons actually run out of neurotransmitter seems unlikely to me. They probably are just not being stimulated to release the dopamine that they keep in storage.
>
> What do you think? Is there any scientific evidence that demonstrates that an SSRI can produce dopamine depletion downstream?The term "dopamine depletion" is in this context certainly a lay simplification intended to describe a subjectively hypodopaminergic state characterized by a reduced capacity to experience pleasure, diminished arousal, etc. I agree that it would be more accurate to describe this as a "functional deficiency" of dopamine, which is more encompassing.
Posted by garnet71 on April 19, 2009, at 16:06:36
In reply to Re: Dopamine depletion: A myth? » garnet71, posted by desolationrower on April 14, 2009, at 2:41:01
hey, i make posts sometimes about theories, but everyone is all "UM ENGLISH PLEASE!LOL!"
-d/r
Well I could probably use some of your genious ideas right now....
This is the end of the thread.
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