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Posted by Shawn. T. on September 28, 2005, at 15:17:37
In reply to Does Ectasy Cause Brain Damage and Depression?, posted by Phillipa on September 28, 2005, at 0:34:25
Ecstasy use doesn't influence the development of depressive symptoms in everyone. For instance, Roiser et al. (2005) have found that unlike people with the ss or ls genotype, ecstasy use is not associated with higher Beck Depression Inventory scores in people with the ll genotype of the serotonin transporter gene (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15741482).
Brain damage is the permanent death or degeneration of brain cells. Is there any strong scientific evidence to suggest that ecstasy is causing the permanent death or degeneration of brain cells? The answer to that question is absolutely not. Last year, Wang and colleagues at the National Institute on Drug Abuse published a report of a groundbreaking study that suggests that MDMA does not induce serotonin nerve terminal degeneration (http://www.erowid.org/references/refs_view.php?A=ShowDoc1&ID=6384). The drug decreases serotonin levels and decreases the amount of serotonin transporters associated with the plasma membrane, but no one has ever shown that it causes any permanent damage to serotonin nerve terminals. MDMA can induce hepatotoxicity, hyperthermia, and other health problems, so it is associated with health risks that should be taken seriously.
Posted by alohashirt on September 28, 2005, at 23:00:19
In reply to Does Ectasy Cause Brain Damage and Depression?, posted by Phillipa on September 28, 2005, at 0:34:25
> Know this sounds wierd coming from me. But I just watched a TV show where someone almost died from ectasy. Said it can cause depression or organ damage. Is it true? Fondly, Phillipa
> Know this sounds wierd coming from me. But I just watched a TV show where someone almost died from ectasy. Said it can cause depression or organ damage. Is it true? Fondly, Phillipa
I think (as is usally the case with interesting questions) the answers are nuanced. When someone takes any illicit drug they have no certyainty that they are really consuming what they think they bought - but I don't think that's what you're discussing.
There have been a number of sudden deaths in people who took ecstacy, sometimes for the first time. Some of these deaths have been attributed to an idiosyncratic reaction involving over-heating.
There have been no controlled studies of MDMA and little serious research about pschiatric uses of MDMA since the drug was classified as schedule 1 in an emergency hearing.
There has been some extremely poor research on MDMA risks to brains. George Ricaurte published a famous NIDA funded study showing neurotoxicit in animals. Unfortunately he to retract the paper because, in fact, mdma was not actually used in the experiment in question. The following link has some interesting data http://www.erowid.org/chemicals/mdma/mdma_media1.shtml
What is clear is that MDMA is much safer than nicotine or acohol
Posted by sleepygirl on September 28, 2005, at 23:09:50
In reply to Does Ectasy Cause Brain Damage and Depression?, posted by Phillipa on September 28, 2005, at 0:34:25
eh...I don't know too much about this, but I've met a few people who took this drug on a regular basis and are quite mentally ill right now - perhaps a coincidence - never a good idea for those predisposed to abuse too many drugs
Posted by djmmm on September 29, 2005, at 7:35:13
In reply to Re: Does Ectasy Cause Brain Damage and Depression?, posted by sleepygirl on September 28, 2005, at 23:09:50
> eh...I don't know too much about this, but I've met a few people who took this drug on a regular basis and are quite mentally ill right now - perhaps a coincidence - never a good idea for those predisposed to abuse too many drugs
You must also take into consideration the many adulterants found in what is sold as "ecstasy"-- mainly methamphetamine.
Also, most peolple that use ecstasy, are polydrug users. These two combining factors make it nearly impossible to accurately determine if MDMA is "neurotoxic" in humans.
I tend to believe, since MDMA is a ring-substituted amphetamine, chronic use/overuse probably causes problems (both neurologic and cardovascular)-- however, there are a few ring-substituted amphetamines (4-methoxyamphetamine, 4-ethoxyamphetamine) that are devoid of neurotoxic effects.
Posted by SLS on September 29, 2005, at 8:05:28
In reply to Re: Does Ectasy Cause Brain Damage and Depression?, posted by alohashirt on September 28, 2005, at 23:00:19
> The following link has some interesting data http://www.erowid.org/chemicals/mdma/mdma_media1.shtml
That link has some interesting allusions to the existence of data, but no citations to the data itself regarding the neurotoxicity of MDMA. The article seems to me to be more a critique of existing critiques.
> What is clear is that MDMA is much safer than nicotine or acohol
I believe this is still a matter of opinion and open to investigation rather than being a self-evident, clear, and unambiguous conclusion.
MDMA is a dangerous drug in high dosages, and much more apt to cause fatalities when abused recklessly than nicotine or alcohol. It has a very long half-life and its pharmacokinetics are not linear due to its saturation of liver enzymes. When used in overdose, MDMA does cause the major organs to shut down. This is probably due to hyperthermia, hepatonecrosis, and rhabdomyolysis. Perhaps this is what Phillipa was referring to.
Regarding neurotoxicity, I haven't committed enough study time to refute the great bulk of studies that suggest that MDMA causes damage at serotonin synaptic terminals. At this time, however, I would worry that if methamphetamine (MA) produces neurotoxicity (I'm not convinced that it does), so might methylenedioxy-methamphetamine (MDMA).
- Scott
Posted by SLS on September 29, 2005, at 8:49:15
In reply to Re: Does Ectasy Cause Brain Damage and Depression? » alohashirt, posted by SLS on September 29, 2005, at 8:05:28
Here's a Medline search:
The keywords used were "MDMA AND (neurotoxic OR neurotoxicity OR damage)"
It's something to look at.
- Scott
Posted by SLS on September 29, 2005, at 9:07:33
In reply to Re: Does Ectasy Cause Brain Damage and Depression?, posted by SLS on September 29, 2005, at 8:49:15
Here's a more complete Medline search:
http://tinyurl.com/bw2zf> The keywords used were "MDMA AND (neurotoxic OR neurotoxicity OR toxic OR toxicity OR damage)"
This search produced quite a few more hits.
- Scott
Posted by SLS on September 29, 2005, at 9:14:16
In reply to Ecstacy Neurotoxicity - Use this Medline Search:, posted by SLS on September 29, 2005, at 9:07:33
Posted by ed_uk on September 29, 2005, at 14:15:17
In reply to Re: Does Ectasy Cause Brain Damage and Depression?, posted by djmmm on September 29, 2005, at 7:35:13
I'd like to try MDMA some day
~Ed
Posted by SeekingAdvice on September 29, 2005, at 17:23:43
In reply to Re: Does Ectasy Cause Brain Damage and Depression?, posted by ed_uk on September 29, 2005, at 14:15:17
I did ecstasy on most (not all) weekends for about 2 years, maybe less. If I couldn't get ecstasy I got cocaine, mushrooms, or whatever. There were drug free weekends somewhere in there. Just more drugs in those 2 years than not. You get the picture….
At the time, I made excellent grades and was pretty well-balanced. It wasn't until I got off of it that I had problems with depression and anxiety. I think that it messed up something in my brain. It felt like I used up all my happiness during those 2 years. Like even the reserves were depleted. I felt basically apathetic until I went on meds. I don't know if it was the drugs. And I really hope they didn't have long term effects on me.
One thing I did notice that is weird is that I cannot handle SSRI's. They make me so elated that I want to drink, smoke and just go nuts. I wonder if that is from damaging a part of my brain (dopamine, serotonin- whatever). I know that I used to tolerate SSRI's in the pre-drug use years. (My mom thought I was depressed as a teen. I didn't think so.)
Interesting posts. I'm eager to hear more.
Love,
SeekingAdvice
Posted by Phillipa on September 29, 2005, at 17:25:41
In reply to Re: Does Ectasy Cause Brain Damage and Depression?, posted by SeekingAdvice on September 29, 2005, at 17:23:43
Ed, you would not! Love PJ O
Posted by Phillipa on September 29, 2005, at 17:30:32
In reply to Re: Does Ectasy Cause Brain Damage and Depression? » alohashirt, posted by SLS on September 29, 2005, at 8:05:28
Scott, I did mean organ damage too. To think a TV show lead to so many magnificent minds! Fondly, Phillipa
Posted by med_empowered on September 29, 2005, at 18:53:58
In reply to Re: Does Ectasy Cause Brain Damage and Depression? » SLS, posted by Phillipa on September 29, 2005, at 17:30:32
Ecstasy might cause brain damage but...there's a good bit of debate. The early studies on the effects of E were focused on poly-drug users; they also made liberal use of post-mortem examination of the brain's of these people,without controlling for the ill-effects of other drugs (ex:methamphetamine, cocaine, etc) or illnesses, poor nutrition (common with polydrug users), or injuries. Ecstasy can cause overheating--its always a good idea to drink lots and lots of water if you choose to do it. The biggest problem, though, has been purity; apparently, a number people have died because they were given fake ecstasy that contained dangerous substances. There's research now on using Ecstasy in cases of severe PTSD...I think there is some data on using it in cases of depression, but I'm not sure of that. Anyway, there usually is a pretty sharp drop in mood for a bit after using Ecstasy, but most people recover...in cases where depression does develop, it could be the ecstasy, or it could be the post-ecstasy blues combined with environmental factors and/or pre-existing problems (since people with mood disorder are more likely to use drugs anyway, the odds that drugs will cause problems in these people is probably higher than with the rest of the population).
Posted by alohashirt on September 29, 2005, at 22:54:04
In reply to Re: Does Ectasy Cause Brain Damage and Depression? » alohashirt, posted by SLS on September 29, 2005, at 8:05:28
> > The following link has some interesting data http://www.erowid.org/chemicals/mdma/mdma_media1.shtml
>
> That link has some interesting allusions to the existence of data, but no citations to the data itself regarding the neurotoxicity of MDMA. The article seems to me to be more a critique of existing critiques.
>
> > What is clear is that MDMA is much safer than nicotine or acohol
>
> I believe this is still a matter of opinion and open to investigation rather than being a self-evident, clear, and unambiguous conclusion.
>
> MDMA is a dangerous drug in high dosages, and much more apt to cause fatalities when abused recklessly than nicotine or alcohol. It has a very long half-life and its pharmacokinetics are not linear due to its saturation of liver enzymes. When used in overdose, MDMA does cause the major organs to shut down. This is probably due to hyperthermia, hepatonecrosis, and rhabdomyolysis. Perhaps this is what Phillipa was referring to.
>
> Regarding neurotoxicity, I haven't committed enough study time to refute the great bulk of studies that suggest that MDMA causes damage at serotonin synaptic terminals. At this time, however, I would worry that if methamphetamine (MA) produces neurotoxicity (I'm not convinced that it does), so might methylenedioxy-methamphetamine (MDMA).
>
>
> - Scott
>Scott - look at the numbers. In the US we have between 75,000 and 100,000 annual deaths attributed to alcohol related causes. Thats about 750 deaths per million. At the same time we have between one and seven deaths per million attributed to ecstasy. There is a tremendous amount of panic and rhetoric about the dangers of substance A or B (think ecstacy, Ritalin, steroids, ...) that just isn't backed up by data. If (any of these) are as dangerous as the worry-mongers suggest, where are the bodies? We know where the bodies of alcohol and nicotine related deaths are - I bet you could find one right now at your local ER if you went there. But vested interests and well-intentioned people ignore the elephant in the living room and focus on polishing the table leg caps.
Posted by SLS on September 30, 2005, at 11:06:22
In reply to Re: Does Ectasy Cause Brain Damage and Depression?, posted by alohashirt on September 29, 2005, at 22:54:04
Hi.
> Scott - look at the numbers. In the US we have between 75,000 and 100,000 annual deaths attributed to alcohol related causes. Thats about 750 deaths per million. At the same time we have between one and seven deaths per million attributed to ecstasy. There is a tremendous amount of panic and rhetoric about the dangers of substance A or B (think ecstacy, Ritalin, steroids, ...) that just isn't backed up by data. If (any of these) are as dangerous as the worry-mongers suggest, where are the bodies? We know where the bodies of alcohol and nicotine related deaths are - I bet you could find one right now at your local ER if you went there. But vested interests and well-intentioned people ignore the elephant in the living room and focus on polishing the table leg caps
From what I can see, your statistic regarding fatalities produced by toxic amounts of the MDMA compound itself is accurate. In the US, between the years 1999 and 2001, a total of 102 drug-induced fatalities were declared by coroners. This translates to about 8 fatalities per million people in the general population. In addition, the study I cite here demonstrates a steep increase in toxic fatalities over this 3 year period. I wonder what it would be for 2004. Importantly, however, is that this statistic does NOT represent 8 fatalaties per million MDMA USERS. It represents fatalaties amongst the entire population. The true question is how frequently do fatalities occur among MDMA users.http://www.aemj.org/cgi/content/abstract/11/2/208
Of course alcohol is going to be implicated in the behavior of more people in the general population! The number of alcohol users are orders of magnitude higher than users of MDMA. Additionally, there is a problem with the statistic you cited. It includes all alcohol-RELATED fatalities, including the deaths of all people killed in auto accidents. It does not represent the number of deaths produced by alcohol toxicity.
"Alcohol-induced mortality
In 1999 a total of 19,171 persons died of alcohol-induced causes in the United States (table 21). The category ‘‘alcohol-induced causes’’ includes not only deaths from dependent and nondependent use of alcohol but also accidental poisoning by alcohol. It excludes accidents, homicides, and other causes indirectly related to alcohol use as well as deaths due to fetal alcohol syndrome."
Alcohol toxicity = 68 deaths per 1,000,000.
http://www.cdc.gov/nchs/data/erratas/nvsr49_08p10.pdf
If we move away from the issue of toxic fatalities and towards that of the potential toxic effects MDMA might have amongst the living, I think this would be more relevant to those considering its use.
- Scott
Posted by Nickengland on September 30, 2005, at 17:19:31
In reply to Does Ectasy Cause Brain Damage and Depression?, posted by Phillipa on September 28, 2005, at 0:34:25
The thing is with ecstacy (MDMA) is what has already probably been said in this thread but i'll mention it again
:-) ~ When you take ecstacy (or any street drug) you never know what you are actually taking.
For example, ecstacy maybe produced in large "batches" by *chemists* lets say in this example that 10,000 pills are produced within this certain batch. These pills maybe considered high quality, as in they contain a high ratio of MDMA and little else other drugs mixed in.
Another *chemist* produces another "batch" of lets say 20,000 pills. These also contain MDMA, however the ratio and quality is not the same as the previous batch of 10,000. These also contain a fairly high ratio of amphetamine.... and maybe ketamine, perhaps also heroin just for good measure.
Lastly there is a *chemist* who produces an ecstacy tablet, which contains very little MDMA (he likes to cut his costs and make easy money like a cheap generic drug company lol)
Now, take a group of people who go out to take Ecstacy - which pill will they end up with in this example? One of three..perhaps they might even take a mixture of all three. Out of the group there is a death. How accurate can you see how the death would occur with the varying quaulity of drug? Was alchohol involved? Were other drugs involved, perhaps smoking cannabis, perhaps sniffing cocaine? Although the cause of death maybe considered to be because of MDMA its hard these days when people go out and take these drugs to firstly know what they were taking and would what actually cause the death eg if they didnt have that vodka and 2 beers would they have not died? Needless to say though, taking MDMA all by itself can kill.
One way which is can kill, can depend on how much water you drink. Not enough can kill you. But drinking too much can kill you also.....by drinking too much water when taking ecstacy you can cause you brain to swell inside your skull, you fall into a coma and die....this has happened. Another way is that basically the heart cannot control it and it virtually explodes.
If you speak to people who took ecstacy in the late 80's early 90's they will tell you it was very diferent (or different) from what it is like to take today. they will tell you it was far better back in the early 90's/late 80's. This shows the varying quality once again.
If you speak to people who took prozac back in the early 90's, the thing is the drug was just what it says it was ~ 20mg of fluoxetine, whereas esctacy ~ even though its MDMA, the formulation was different and is always changing depending on the batch.
Also back in the late 80's, early 90's people would generally only need to take 1 tablet. Now days people will go out and take 5 or 6. Again showing the difference in the quality.
Taking ecstacy, MDMA does something to the brain which in a sense you could say is damage depening on how you look at it. It will give you the happiest feeling of your life. The cost of that can be an after effect of depression lasting anywhere from up to a day to a week, not usually longer.
Some people however pick up a cigarette and within 6 months have cancer and die. Some smoke large amounts for 50 years plus and never even seem to have a cough and be as fit as a fiddle.
Likewise with ecstacy, they are some, they can take 1 single tablet and it could kill them then and there. At the same time this weekend in the UK hundreds of thousands of people will consume the drug and not be hardly effected from the after effects by monday morning and will repeat what they've done again in a week or 2, and these same people have been doing this for the past few years.
I'd say yes, esctacy in certain cases can cause Brain damage, depression and death. (depending on quality and dosage)
Also i'd say that many other drugs (legal) can cause in certains cases brain damage, depression and death. (depending on dosage - however the quality is what it says on the box ~ the quality of ecstacy is what your told it is by the dealer or other people who have taken the substance, unless you have a good relationship with the manufacturing *chemist* which would be very rare.
Posted by Shawn. T. on September 30, 2005, at 17:35:59
In reply to Re: Does Ectasy Cause Brain Damage and Depression?, posted by Nickengland on September 30, 2005, at 17:19:31
"I'd say yes, esctacy in certain cases can cause Brain damage..."
Could you please cite a peer-reviewed reference that supports your claim?
Shawn
Posted by Nickengland on September 30, 2005, at 18:27:20
In reply to Re: Does Ectasy Cause Brain Damage and Depression? » Nickengland, posted by Shawn. T. on September 30, 2005, at 17:35:59
Hi Shawn
>Could you please cite a peer-reviewed reference that supports your claim?
Yes. The brain damage im refering to in certain cases is that of brain swelling which leads to coma and death. Where I live in the UK and when I was at school back in 95 a girl died of this way by taking MDMA. It was her first time. Although the water caused the brain to swell ~ taking the MDMA caused her to drink so much water in the first place. Not alot of people are worried about drinking water that their brain might swell and put them in a coma, but give someone ecstacy and this is a very real danger and has happened. I remember this particular incident as this particular girls father came to my school to give us a talk on the danger of the drug after her daughter had died. He also went around the whole of the UK making children aware of the dangers as to not have this happen again, there was much media attention.
Taken from
http://www.drugsinfofile.com/ecstasy.html
Brain swelling
Because you're so hot, you may drink too much water too quickly. This can cause the brain to swell, leading to unconsciousness and rapid death (within 12 hours).Thats what I was refering to when I used the term brain damage, albeit losely but having your brain swell does sound quite damaging to me!
Also it says..
Brain damage
Ecstasy can interrupt blood flow to the brain and cause a stroke (yes, even in young people), resulting in paralysis, dementia (loss of memory and the ability to think clearly) and Parkinson's disease (when the body shakes and twitches uncontrollably).And from some other souces ..
Ecstasy" Damages the Brain and Impairs Memory in Humans
http://www.drugabuse.gov/NIDA_Notes/NNVol14N4/Ecstasy.html
Ecstasy brain damage link
http://news.bbc.co.uk/2/hi/health/1076381.stm
Health
Ecstasy link to brain damage
http://news.bbc.co.uk/1/hi/health/203784.stm
Persistent neuropsychological problems after 7 years of abstinence from recreational Ecstasy (MDMA): a case study
http://mdma.net/toxicity/ex-user.html
The death I was refering too...
Perhaps the most high profile ecstasy victim was Leah Betts of Latchingdon, Essex who died in November 1995 after taking the drug at her 18th birthday party.
http://news.bbc.co.uk/1/hi/uk/1319460.stm
http://news.bbc.co.uk/1/hi/education/1848638.stm
http://news.bbc.co.uk/1/hi/scotland/693267.stm
Kind regards
Nick
Posted by Phillipa on September 30, 2005, at 19:17:00
In reply to Re: Does Ectasy Cause Brain Damage and Depression? » Shawn. T., posted by Nickengland on September 30, 2005, at 18:27:20
Nick, it sounds like DIC disseminated incoagulation . When the body bleeds out of every orifice and nothing can stop it. The clotting mechanism will no longer work. And death is imminent. Fondly, Phillipa
Posted by SLS on October 1, 2005, at 10:13:02
In reply to Re: Does Ectasy Cause Brain Damage and Depression? » Nickengland, posted by Shawn. T. on September 30, 2005, at 17:35:59
> "I'd say yes, esctacy in certain cases can cause Brain damage..."
>
> Could you please cite a peer-reviewed reference that supports your claim?
>
> Shawn
Hi Shawn.How do you feel about the many, many studies that report neurotoxicity produced by MDMA in animals?
Semantically speaking, do you consider neurotoxicity a form of brain damage?
- Scott
Posted by SLS on October 1, 2005, at 10:25:52
In reply to Re: Does Ectasy Cause Brain Damage and Depression? » Nickengland, posted by Shawn. T. on September 30, 2005, at 17:35:59
Hi Shawn.
How do you feel about the potential for fenfluramine to damage serotonergic neurons as is often reported?
- Scott
Posted by Shawn. T. on October 1, 2005, at 18:44:24
In reply to Re: Does Ectasy Cause Brain Damage and Depression? » Shawn. T., posted by Nickengland on September 30, 2005, at 18:27:20
Cases of brain swelling due to MDMA are rare. I imagine that just as many people die of brain swelling caused by excessive drinking during physical exertion. But that is a good point, and people should know better than to drink too much water. There are some cerebrovascular risks as well, but such problems are also not common. My main point is that the sort of brain damage commonly associated with MDMA, neurotoxicity involving serotonin neurons, is not well-supported by scientific evidence. Finding a decreased number of serotonin transporters with PET imaging does not imply brain damage. Tests where people are deprived of tryptophan cannot diagnose brain damage. Findings that suggest that MDMA can cause long-term neuropsychological problems do not imply brain damage. There's simply no evidence available that shows that MDMA causes the death or degeneration of serotonin neurons.
Shawn
Posted by Shawn. T. on October 1, 2005, at 18:53:05
In reply to Re: Does Ectasy Cause Brain Damage and Depression? » Shawn. T., posted by SLS on October 1, 2005, at 10:25:52
On the matter of neurotoxicity, I feel that people, especially non-scientists, often jump to conclusions about evidence that they haven't carefully considered. According to Rothman et al. (2004) at the National Institute on Drug Abuse, D-fenfluramine and parachloroamphetamine "did not change expression of glial fibrillary acidic protein (GFAP), a hallmark indicator of neuronal damage, in whole brain minus caudate in the 2-week group. These results support the hypothesis that D-FEN- and PCA-induced decreases in tissue 5-HT and SERT binding sites reflect neuroadaptive changes rather than neurotoxic effects."
Shawn
Posted by Nickengland on October 1, 2005, at 20:17:38
In reply to Re: Does Ectasy Cause Brain Damage and Depression? » Nickengland, posted by Shawn. T. on October 1, 2005, at 18:44:24
Hi Shawn,
>Cases of brain swelling due to MDMA are rare.
Yes, definitely I agree.
>I imagine that just as many people die of brain swelling caused by excessive drinking during physical exertion.
What kind of physical exertion?...the kind which is increased by the effects of MDMA where people dance non stop till 6:00am? lol
>people should know better than to drink too much water.
Judging from the brain damage that was caused from MDMA in the case of Leah Betts on her taking ecstacy, its very good in a very sad sense, that now alot of people do know better through her death of water intake linked with MDMA that occured..
>My main point is that the sort of brain damage commonly associated with MDMA, neurotoxicity involving serotonin neurons, is not well-supported by scientific evidence. Finding a decreased number of serotonin transporters with PET imaging does not imply brain damage.
Ahhh I see... My point of brain damage was completely different. Nothing to do with serotonin. I guess its probably fair to say that the drug does not damage some areas of the brain but it does have the potential to damage other parts. Perhaps my point is, ecstacy can cause the brain to swell as in some rare cases because the need for extra water intake, therefore it will cause the person to fall into a coma, which is brain damage.
Kind regards
Nick
Posted by SLS on October 1, 2005, at 22:37:01
In reply to Re: Does Ectasy Cause Brain Damage and Depression? » SLS, posted by Shawn. T. on October 1, 2005, at 18:53:05
Hi Shawn.
> On the matter of neurotoxicity, I feel that people, especially non-scientists, often jump to conclusions about evidence that they haven't carefully considered.
I'm sure some people do. I'm sure some people don't. I'm betting on our neuroscientists to carefully consider the evidence while that evidence evolves as our experiments are refined and our understanding expands.
> According to Rothman et al. (2004) at the National Institute on Drug Abuse, D-fenfluramine and parachloroamphetamine "did not change expression of glial fibrillary acidic protein (GFAP), a hallmark indicator of neuronal damage,
Are there any other putative indicators that they did not assay for that perhaps don't depend on glial cells to reflect?
> These results support the hypothesis that D-FEN- and PCA-induced decreases in tissue 5-HT and SERT binding sites reflect neuroadaptive changes rather than neurotoxic effects."
Interesting way of looking at things. This might be very true. However, this one aspect of neuronal function and adaptation does not exclude the possibility that toxic events are not localized elsewhere in the neuron. What about the synaptic vesicles, their transporters, and the areas of the terminal membrane upon which they fuse? Perhaps more importantly, if the reduction in transporter numbers is also reflected in synaptic vesicles, there might be an inability for the neuron to sequester neurotransmitter at a rate high enough to prevent its oxidation in the cytosol and the subsequent release of free radicals that produce a degeneration of neurites. I don't happen to know if GFAP acts as an index of this type of neurotoxicity.
In the absence of absolute knowledge and understanding, I guess it becomes an exercise in logic as to what we may conclude absolutely. If GFAP appears, we have neurotoxicity. If GFAP does not appear, we don't?
Devil's advocate.
- Scott
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