Dopamine, the contradiction

[dimulants]

Has anyone noticed that dopamine dysfunction is considered to be mainly related to disorders that don't mainly, or necessarily at all, relate to mood and energy?

At the same time, virtually every stimulant that acts on dopamine is famous for boosting mood, alertness and energy, such as stimulants, speed, cocaine, meth, etc.


This seems to me almost bizarre, because dopamine medications are mainly given for adhd, parkinsons, psychosis maybe even restless leg syndrome, but hardly at all for mood disorders. So which is it, you wonder, are we speaking two different types of dopamine?


Btw, at the same time serotonin is widely considered to be a mood related neurotransmitter (in the clinical field almost exclusively, that is), even though studies show that decreasing serotonin does not cause a drop in mood nor depression. 8(


What gives, anyone has any idea?

 

[neversickanymore]

DS --> OD

Im not sure how much dopamine is specifically and solely related to mood. The stimulants you mention all effect other receptors and neurotransmitter levels.

 

[theedeadmau5]

dopamine is responsible for reward-like feelings, sexual arousal, gratification, things like that. that is a bit different than mood elevations, which is what serotonin is responsible for, although they can work together simultaneously. dopamine agonists have been proven to work for parkinson's and naturally occurring RLS. SSRIs and SNRIs are used for depression(mood elevation). SSRIs are prescribed for people that may suffer from naturally low serotonin levels, although SOME is being produced. so when you take drugs like prozac and zoloft for an extended period of time it helps the body produce serotonin. however if you stop it the meds, the body will NOT PRODUCE ANY serotonin, thus causing major depression worse than what the person was experiencing before.

 

[dimulants]

Unfortunately I do not believe in the serotonin theory of depression. You may be interested in knowing that research has also proven that serotonin deficiency doesn't cause depression. Imo, big pharma is 99% responsible for the serotonin theory, since it has been used mainly in the promotion of newer antidepressants.

As for reward that's another thing about dopamine. Since dopamine regulates reward and pleasure (in that feeling reward couldn't be accompanied by dysphonia), what does parkinsons have to do with reward? Based on current information it seems dopamine on one hand regulates motor function (parkinsons, restless leg syndrome), on another hand focus (ADHD), and on another perception (psychosis) and yet on another, reward (this is where depression would fit in, but for some suspect reason is mainly only mentioned under serotonin, and norepinephrine). That's the war on drugs, causing depression sufferers to be deprived of potential life savers. It's as if, if you die so be it, don't touch dopamine, that's BAD. This leads many sufferers to self-medicate, which is far worse. Is serotonin deficiency isn't the problem for those, of course they won't stick with ssri. (Sorry to venture off a bit, but looking up dopamine and depression is what made me notice the seemingly contradictory information). They hand out dopamine stimulants to about everyone, except for the depressed, as if it's bad to feel good. If you're obese or have problems focusing, here's some speed for you. If you're depressed, here's another ssri, even if they patently don't work. Oh you still feel like sh**? O well, gotta give these serotonin boosters some time, give em another decade then we'll try some NRI's, if you're still alive. No dope for the depressed, who arguably need it the most out of the bunch, depression being a suicidal condition.

Since cocaine was one of the few substances that helped with my depression symptoms, I got interested in dopamine reuptake inhibitors for depression, but found out that there's virtually none, even though dopamine stimulants are known to improve depressive symptoms. Again, it turned out virtually all prescribed DRIs are for adhd, psychosis and parkinsons. I was like, kay, so cocaine helps with psychosis then? Also, even though there are ssri for depression, people self-medicate with dopamine stimulants. There are no addcits that seek serotonin pills. Wouldn't you think that strong serotonin reuptakers would induce euphoria if serotonin is a 'feel-good' chemical? No, but that applies to dopamine. Wellbutrin is a weak DRI that helps some with depression. Cocaine is a strong DRI that's moving a worldwide elicit market due to its feel good effects.
Btw, there are a few DRI antidepressants, namely tricyclics that work on dopamine, all banned in the US.
So all this points to dopamine being responsible for antidepressant feelings (energy, alertness, focus, reward, euphoria), yet all DRI here are for non mood related disorders. It would seem either something is fishy, or research science has tripped on itself on dopamine, calling it the reward neurotransmitter and/or the motor function neurotransmitter, or the perception neurotransmitter or the focus neurotransmitter.

But that can be said about serotonin as well, in the case of ssri which are being prescribed for so many disorders, besides depression, and tricyclic serotonin reuptake inhibitors are even being prescribed for physical pain8(. I just hoped someone might have known whether dopamine is responsible for reward or motor function, or both and/or more. But I suppose theories are most we have at the moment. But it seems cocaine would have a major impact on parkinsons and pshychosis, by either worsening or improving symptoms if dopamine was their culprit. Imo, what we do know is that dopamine is a culprit in depression given cocaine's ability to increase drive, motivation, alertness and well being, all of which are absent in major depression. Thanks for your input.

 

[St3ve]

As for reward that's another thing about dopamine. Since dopamine regulates reward and pleasure (in that feeling reward couldn't be accompanied by dysphonia), what does parkinsons have to do with reward? Based on current information it seems dopamine on one hand regulates motor function (parkinsons, restless leg syndrome), on another hand focus (ADHD), and on another perception (psychosis) and yet on another, reward (this is where depression would fit in, but for some suspect reason is only mentioned under serotonin, and norepinephrine).

Well there are multiple areas in the brain that contain dopaminergic neurons. Dopamine does not carry out the exact same function in each area. The motor related issues with dopamine are due to misbehaving neurons in the nigrostriatal pathways. Reward related stuff occurs in the mesolimbic pathway, psychosis is probably in some sense related to this pathway as is the focus thing from cocaine/ritalin/amphetamines. Then you have the meso-cortical pathway which goes from midbrain structures to the frontal areas of the cortex, this has got to do with decision making, perception and addiction, also involved in psychosis and focus. Then there is one more pathway called the tuberoinfundibular pathway which has got to do with control of hormonal release, not sure how relevant this one is to the questions you had.

I hope that sort of gives you an idea, googling dopaminergic pathways will give you much more in depth information .

 

[dimulants]

Well there are multiple areas in the brain that contain dopaminergic neurons. Dopamine does not carry out the exact same function in each area. The motor related issues with dopamine are due to misbehaving neurons in the nigrostriatal pathways. Reward related stuff occurs in the mesolimbic pathway, psychosis is probably in some sense related to this pathway as is the focus thing from cocaine/ritalin/amphetamines. Then you have the meso-cortical pathway which goes from midbrain structures to the frontal areas of the cortex, this has got to do with decision making, perception and addiction, also involved in psychosis and focus. Then there is one more pathway called the tuberoinfundibular pathway which has got to do with control of hormonal release, not sure how relevant this one is to the questions you had.

I hope that sort of gives you an idea, googling dopaminergic pathways will give you much more in depth information .

Well there are multiple areas in the brain that contain dopaminergic neurons. Dopamine does not carry out the exact same function in each area. The motor related issues with dopamine are due to misbehaving neurons in the nigrostriatal pathways. Reward related stuff occurs in the mesolimbic pathway, psychosis is probably in some sense related to this pathway as is the focus thing from cocaine/ritalin/amphetamines. Then you have the meso-cortical pathway which goes from midbrain structures to the frontal areas of the cortex, this has got to do with decision making, perception and addiction, also involved in psychosis and focus. Then there is one more pathway called the tuberoinfundibular pathway which has got to do with control of hormonal release, not sure how relevant this one is to the questions you had.

I hope that sort of gives you an idea, googling dopaminergic pathways will give you much more in depth information .

That was very relevant, thanks. That makes some sense of the confusion. So basically neurotransmitters can be thought of as take, water, which quenches thirst if ingested, cooks if boiled, rinses if poured, etc? So it's not merely a fallback theory like with serotonin, which sounds reassuring.


Now, there's just the gap of dopamine behind depression. I'm quiet baffled by the gasping lack of DRIs for depression, it's really saying "depression is secondary to our prejudices about addiction". When a drug is used to treat symptoms, chances are addiction isn't a big risk. If someone with depression had to take a stimulant for the rest of their lives, then so be it if without it crippling symptoms returned. It's obviously already done in the areas of physical pain (opiates), and other psychiatric disorders like ADHD. Do they call it addiction when someone with ADHD keeps taking Adderall for years, and comes back for more? Seeking a 'high' is completely different from seeking symptom relief, which for some obnoxious reason doesn't seem to apply to the depressed, suggesting those behind it partake in the stigma surrounding the condition as in not considering it a real illness, otherwise I don't see how they would consciously withhold potential relief in the case of DRIs. Now ketamine is facing some of that obnoxious crowd, although hopefully Yale and Stanfords studies and the credibility they'll lend to it will hopefully put that crowd into silence. Maybe I should try to become obese, then I may get some Adderall prescribed, as opposed to if I was 'merely' suicidal, in which case ineffective ssri will be prescribed in the make-belief that you're being helped. Thanks, but I already know where to find 5-htp pills for serotonin, may not sound as lofty as 'prozac', but serotonin it boosts. And it works jack sh**. No kidding, right, find one drug dealer that deals serotonin boosters and I'll pay you $500. Even ethanol comes before serotonin in the self medication department. Sounds like serotonin might not be all it's cracked up to be after all, right? Been on more than a handful of ssri btw. Thanks to their uselessness I don't view psychiatrists as 'worthy' as ordinary doctors anymore, since a plain doctor that keeps prescribing meds that patently don't work, and that has science backing up their ineffectiveness, is probably unheard of.

As I mentioned above, research has shown that ssri improve depressive symptoms by regrowing brain connections, rather than boosting serotonin, as big pharma wanted us to believe. They'll keep peddling serotonin, until the new research findings become more widely known, even though it's a patently false theory. On that note, I also think that many who're helped by ssri feel placebo. The placebo effect of ssri must be significant since both pharmacists and psychiatrists advocate them, plus the tv and print ads on them by the supposedly legit pharmaceutical companies. It's not just a random person or friend insisting they work, which could have been enough for a placebo effect.

Thanks for clearing out on dopamine. It was relieving to hear that, at least, that made sense .

 

[dimulants]

Well there are multiple areas in the brain that contain dopaminergic neurons. Dopamine does not carry out the exact same function in each area. The motor related issues with dopamine are due to misbehaving neurons in the nigrostriatal pathways. Reward related stuff occurs in the mesolimbic pathway, psychosis is probably in some sense related to this pathway as is the focus thing from cocaine/ritalin/amphetamines. Then you have the meso-cortical pathway which goes from midbrain structures to the frontal areas of the cortex, this has got to do with decision making, perception and addiction, also involved in psychosis and focus. Then there is one more pathway called the tuberoinfundibular pathway which has got to do with control of hormonal release, not sure how relevant this one is to the questions you had.

I hope that sort of gives you an idea, googling dopaminergic pathways will give you much more in depth information .

That was very relevant, thanks. That makes some sense of the confusion. So basically neurotransmitters can be thought of as take, water, which quenches thirst if ingested, cooks if boiled, rinses if poured, etc.


Now, there's just the gap of dopamine behind depression left. I'm quiet baffled by the gasping lack of DRIs for depression, it's really saying "depression is secondary to our prejudices about addiction". When a drug is used to treat symptoms, chances are addiction isn't a big risk. If someone with depression had to take a stimulant for the rest of their lives, then so be it if without it crippling symptoms returned. It's obviously already done in the areas of physical pain (opiates), and other psychiatric disorders like ADHD. Do they call it addiction when someone with ADHD keeps taking Adderall for years, and comes back for more? Seeking a 'high' is completely different from seeking symptom relief, which for some obnoxious reason doesn't seem to apply to the depressed, suggesting those behind it partake in the stigma surrounding the condition as in not considering it a real illness, otherwise I don't see how they would consciously withhold potential relief in the case of DRIs. Now ketamine is facing some of that obnoxious crowd, although hopefully Yale and Stanfords studies and the credibility they'll lend to it will hopefully put that crowd into silence. Maybe I should try to become obese, then I may get some Adderall prescribed, as opposed to if I was merely suicidal, in which case ineffective ssri will be prescribed in the make-belief that you're being helped. Thanks, but I already know where to find 5-htp for serotonin, may not sound as lofty as 'prozac', but serotonin it boosts. And it works jack sh**. No kidding, right, find one drug dealer that deals serotonin boosters and I'll pay you $500. Even ethanol comes before serotonin in the self medication department. Sounds like serotonin might not be all it's cracked up to be after all, right? Been on more than a handful of ssri btw. Thanks to their uselessness I don't take psychiatrists as seriously as other medical professionals as a result, since a regular doctor that keeps prescribing meds that patently don't work, and that has science backing up their ineffectiveness, is probably unheard of.

As I mentioned above, research has shown that ssri improve depressive symptoms by regrowing brain connections, rather than boosting serotonin, as big pharma wanted us to believe. They'll keep peddling serotonin, until the new research findings become more widely known, even though it's a patently false theory. On that note, I also think that many who're helped by ssri feel placebo. The placebo effect of ssris must be significant since both pharmacists and psychiatrists advocate them, plus the tv and print ads on them by the supposedly legit pharmaceutical companies. Plus there's a study showing that ssri may not be effective in mild to moderate depression.

Thanks for clearing out on dopamine. It was relieving to hear that that made sense, at least . Was starting to wonder if dopamine was part of the serotonin deception scheme.

 

[VitamaN]

I know this = no coffee = no dopamine for me = not happy. Caffeine doesn't wake me up. I wake up on my own...
it keeps me from being a depressed lil bish

 

[DarkGhost101]

Dopamine is a neurotransmitter responsible for motivation (incentive salience, or "wanting" something), not pleasure ("liking" something).
The good feeling that dopamine causes is not euphoria, it is what motivation feels like. It makes you feel good, energetic and highly focused, in order to make it easier for you to achieve your goal.

When you do reach your goal, the brain is flooded with endorphins, which are chemically similar to opiates, and thus they bind to the mu-opioid receptors in the brain. This flood of endorphins causes euphoria, which is characterized by calmness and optimism. Real euphoria (like endorphins cause) is sedating and calming, not stimulating. The simplest example I can give is sex - during sex, the brain is flooded with dopamine to help you keep going. When you reach orgasm, dopamine levels drop and endorphins flood the brain, causing a calm euphoric feeling of well-being.

So to make things short - Dopamine plays a very significant role in mood, because it causes motivation. With low levels of dopamine, you'll find yourself have a hard time focusing (not enough motivation for focusing on a task) and get easily bored (not enough motivation to make an effort to enjoy something).

Depression can be caused by low levels of serotonin. Low levels of dopamine causes a lack of motivation, which is sometimes confused for depression. For example, people with low levels of dopamine appear depressed because they don't want to go out with their friends. But they might not be actually depressed. In fact, most of them would have a great time being with their friends, it's just that they don't have enough motivation to make an effort to actually go see their friends.

Low levels of serotonin characterizes real depression. I don't know where you've read these researches, but serotonin is highly important for mood stabilization. Drugs which act on serotonin, like MDMA and LSD, cause feelings of extreme happiness because they affect serotonin. Also, you might have heard that SSRIs don't work for many people - it might be because these people are suffering from low levels of dopamine, not low levels of serotonin.

 

[theedeadmau5]

lol so basically you are trying to disprove of decades of research that concludes low serotonin levels are responsible for depression. seems a bit heroic ?

 

[St3ve]

lol so basically you are trying to disprove of decades of research that concludes low serotonin levels are responsible for depression. seems a bit heroic ��

The monoamine hypthesis is currently going out of favour. There's too many aspects of depression it doesn't cover. One of the main reasons it came about was that people discovered SSRIs and other serotonin increasing meds were effective in treating depression. People figured, well if drugs that increase serotonin fix depression, depression in it self must be low levels of serotonin.

Like most things in the brain, it's not that simple. SSRIs are aborbed rapidly and work within hours of dosing. Yet the anti-depressant effect doesn't set in until weeks later. This has nothing to do with the effect of the SSRI accumulating and more and more serotonin being pushed into the synaptic cleft until you reach a certain treshold of serotonin levels. Rather it has to do with the downstream effects of increased serotonin binding to a subset of serotonin receptors. These change the way the cells work, and in the long run decrease the amount of stress hormones in the body. These are now thought to be the "real" cause behind depression. Chronic elevation of stress hormones causes loss of neurons in the hippocampus, SSRI's in part, work by fixing this loss of neurons here.

Interestingly, dopamine is also beginning to be respected as playing a crucial role in depression. Not suprisingly, as DarkGhost101 explained (I'm glad to see someone else here has read Berridge's work on dopamine ), one of dopamine's main roles is causing the sensation of motivation. Depressed people often have problems getting out of bed and don't see the point in doing anything.

Ketamine treatment for depression indirectly works on dopamine, in a similar way SSRIs work on stress hormones. Downstream effects of ketamine binding to NMDA receptors causes a long lasting sensitisation to the dopamine system. Hereby fixing the lack of motivation in the depressed patient and temporarily causing a relief of symptoms.

I think the main reason drugs like adderall are not being prescribed for depression is abuse and lack of long term efficacy. It might work in the short run, but longterm use of amphetamines is only going to induce the depression again.

 

[dimulants]

Dopamine is a neurotransmitter responsible for motivation (incentive salience, or "wanting" something), not pleasure ("liking" something).
The good feeling that dopamine causes is not euphoria, it is what motivation feels like. It makes you feel good, energetic and highly focused, in order to make it easier for you to achieve your goal.

When you do reach your goal, the brain is flooded with endorphins, which are chemically similar to opiates, and thus they bind to the mu-opioid receptors in the brain. This flood of endorphins causes euphoria, which is characterized by calmness and optimism. Real euphoria (like endorphins cause) is sedating and calming, not stimulating. The simplest example I can give is sex - during sex, the brain is flooded with dopamine to help you keep going. When you reach orgasm, dopamine levels drop and endorphins flood the brain, causing a calm euphoric feeling of well-being.

So to make things short - Dopamine plays a very significant role in mood, because it causes motivation. With low levels of dopamine, you'll find yourself have a hard time focusing (not enough motivation for focusing on a task) and get easily bored (not enough motivation to make an effort to enjoy something).

Depression can be caused by low levels of serotonin. Low levels of dopamine causes a lack of motivation, which is sometimes confused for depression. For example, people with low levels of dopamine appear depressed because they don't want to go out with their friends. But they might not be actually depressed. In fact, most of them would have a great time being with their friends, it's just that they don't have enough motivation to make an effort to actually go see their friends.

Low levels of serotonin characterizes real depression. I don't know where you've read these researches, but serotonin is highly important for mood stabilization. Drugs which act on serotonin, like MDMA and LSD, cause feelings of extreme happiness because they affect serotonin. Also, you might have heard that SSRIs don't work for many people - it might be because these people are suffering from low levels of dopamine, not low levels of serotonin.

No, low levels of serotonin does not characterize real depression. It's not particularly brave to state that. Recent findings have found ssri no better than sugar pills for the majority of depressed. Other studies found that medications that decrease serotonin levels do not cause depressive symptoms. I'm a living example, isn't that enough. There was no detectable improvement in mood at all from any of the ssri I took, even after a good 2 months on Zoloft, paxil or Cymbalta, and I didn't skip doses. You'd think pills that boost serotonin, a supposed feel-good neurotransmitter, ought to do 'something' regardless, especially when symptoms are quiet severe, such as with anhedonia and dysphoria. Either that, or it isn't a feel-good chemical.

I totally agree with what you said on dopamine and endorphins. They are real feel-good neurotransmitters, hence even an exhausted runner experiences a rush of well being during a runners-high, and stimulants are effective even for soldiers in war. Opium even led to a war, and crack cocaine led to turf wars. Now, where's serotonin? The supposed feel good neurotransmitter alongside dopamine and endorphins... 5-htp capsules probably aren't even a particularly popular supplement.

But it's not just the many logical holes, there's also research showing that ssri are no better than sugar pills for mild and moderate depression.

And so, it seems that ssri work by regenerating brain connections, rather than correcting a 'chemical imbalance'. What's more, ssri take up to 6 weeks to work, long after boosting serotonin levels.

"In general, the relationships between brain serotonin concentrations and BDNF expression are very complex, but previous studies have suggested that both higher (such as caused by serotonin reuptake inhibitors) and lower (such as effected by tianeptine) concentrations of free serotonin might induce BDNF expression in such brain regions as the frontal and parietal cortex."

http://www.hopkinsmedicine.org/Press_releases/2005/12_19_05.html


So against all those facts, logical holes and research findings, I found out that dopamine, the real feel good neurotransmitter has virtually nothing for it in the antidepressant department, likewise neither do endorphins. It's like they insist on ssris against the facts.

And sure, it might be that some depressed suffer from dopamine deficiency , but it still doesn't answer why serotonin pills don't exist in the drug trade, or why ssris were found ineffective in mild to moderate depression (presumably when neurons aren't yet significantly damaged, thus ssris may have nothing to regrow), or why test subjects who had their serotonin levels lowered didn't become more depressed.

But wait a minute, wouldn't a dopamine deficiency cause Parkinson like symptoms? And wouldn't Parkinson sufferers who take parkison meds (that regulate dopamine) see an improvement in mood, at it. Never mind.

 

[dimulants]

The monoamine hypthesis is currently going out of favour. There's too many aspects of depression it doesn't cover. One of the main reasons it came about was that people discovered SSRIs and other serotonin increasing meds were effective in treating depression. People figured, well if drugs that increase serotonin fix depression, depression in it self must be low levels of serotonin.

Like most things in the brain, it's not that simple. SSRIs are aborbed rapidly and work within hours of dosing. Yet the anti-depressant effect doesn't set in until weeks later. This has nothing to do with the effect of the SSRI accumulating and more and more serotonin being pushed into the synaptic cleft until you reach a certain treshold of serotonin levels. Rather it has to do with the downstream effects of increased serotonin binding to a subset of serotonin receptors. These change the way the cells work, and in the long run decrease the amount of stress hormones in the body. These are now thought to be the "real" cause behind depression. Chronic elevation of stress hormones causes loss of neurons in the hippocampus, SSRI's in part, work by fixing this loss of neurons here.

Interestingly, dopamine is also beginning to be respected as playing a crucial role in depression. Not suprisingly, as DarkGhost101 explained (I'm glad to see someone else here has read Berridge's work on dopamine ), one of dopamine's main roles is causing the sensation of motivation. Depressed people often have problems getting out of bed and don't see the point in doing anything.

Ketamine treatment for depression indirectly works on dopamine, in a similar way SSRIs work on stress hormones. Downstream effects of ketamine binding to NMDA receptors causes a long lasting sensitisation to the dopamine system. Hereby fixing the lack of motivation in the depressed patient and temporarily causing a relief of symptoms.

I think the main reason drugs like adderall are not being prescribed for depression is abuse and lack of long term efficacy. It might work in the short run, but longterm use of amphetamines is only going to induce the depression again.

Well said. Very interesting to hear that ketamine sensitizes receptors to dopamine. Up to now I was thinking of ketamine/glutamate drugs as distinct from dopamine reuptake inhibitors, wondering where known mood neurotransmitters fit into its picture. Thanks for shedding that light. I'm now even more interested in ketamine, up til now thought of it as an option next to stimulants. But would much rather that something without tolerance or addiction would work.

As for dopamine and motivation. When trying coke, I hadn't felt that motivated in years. It led me to look into other dopamine stimulants that are already being rxd for other conditions, including depression, in some cases. Such as Adderall. If coke could do that, make me procrastinate less for its short duration, I wondered what something like amphetamine which lasts much longer could do in a single day. All I know is that without such help, I get very little done including normally necessary things, I just think of my symptoms non stop, and how to relieve them, be it motivation to get things done, or experiencing pleasure, sometimes resorting to alcohol, lots of sweets which probably wreck my blood sugar levels, yet staying depressed just isn't an option. Since ketamine isn't about to become a mainstream treatment anytime soon, I'm hoping to run into an open minded psychiatrist in the meantime. I've been on benzos without problems, I'm sure I could handle Adderall without becoming a drug seeker. Depression itself is rather like a drug abstinence, except lasting. Like with benzos, there'd probably be an optimal state for when taking it, vs skipping at other times. If I could be on that for a year or two, or however long benefits could be sustained, ketamine derived drugs may already be out or close to it by then. If on the other hand, I don't do anything, let alone pretend that another ssri or snri will make a difference, valuable time will be lost.

Btw, sweets, nicotine and alcohol also increase dopamine, I think I've heard. Thus, so far everything points to dopamine being deficient in my case, with coke firmly affirming that idea. Ketamine sounds most interesting though since it doesn't simply boost dopamine, but seems to do some major reworking of the brain connections. That seems more like what I'd need, it's just a pity the effect isn't lasting either.

 

[Euphorogenesis]

Unfortunately I do not believe in the serotonin theory of depression. You may be interested in knowing that research has also proven that serotonin deficiency doesn't cause depression. Imo, big pharma is 99% responsible for the serotonin theory, since it has been used mainly in the promotion of newer antidepressants. As for reward that's another thing about dopamine. Since dopamine regulates reward and pleasure (in that feeling reward couldn't be accompanied by dysphonia), what does parkinsons have to do with reward? Based on current information it seems dopamine on one hand regulates motor function (parkinsons, restless leg syndrome), on another hand focus (ADHD), and on another perception (psychosis) and yet on another, reward (this is where depression would fit in, but for some suspect reason is mainly only mentioned under serotonin, and norepinephrine). That's the war on drugs, causing depression sufferers to be deprived of potential life savers. It's as if, if you die so be it, don't touch dopamine, that's BAD. This leads many sufferers to self-medicate, which is far worse. Is serotonin deficiency isn't the problem for those, of course they won't stick with ssri. (Sorry to venture off a bit, but looking up dopamine and depression is what made me notice the seemingly contradictory information). They hand out dopamine stimulants to about everyone, except for the depressed, as if it's bad to feel good. If you're obese or have problems focusing, here's some speed for you. If you're depressed, here's another ssri, even if they patently don't work. Oh you still feel like sh**? O well, gotta give these serotonin boosters some time, give em another decade then we'll try some NRI's, if you're still alive. No dope for the depressed, who arguably need it the most out of the bunch, depression being a suicidal condition. Since cocaine was one of the few substances that helped with my depression symptoms, I got interested in dopamine reuptake inhibitors for depression, but found out that there's virtually none, even though dopamine stimulants are known to improve depressive symptoms. Again, it turned out virtually all prescribed DRIs are for adhd, psychosis and parkinsons. I was like, kay, so cocaine helps with psychosis then? Also, even though there are ssri for depression, people self-medicate with dopamine stimulants. There are no addcits that seek serotonin pills. Wouldn't you think that strong serotonin reuptakers would induce euphoria if serotonin is a 'feel-good' chemical? No, but that applies to dopamine. Wellbutrin is a weak DRI that helps some with depression. Cocaine is a strong DRI that's moving a worldwide elicit market due to its feel good effects. Btw, there are a few DRI antidepressants, namely tricyclics that work on dopamine, all banned in the US. So all this points to dopamine being responsible for antidepressant feelings (energy, alertness, focus, reward, euphoria), yet all DRI here are for non mood related disorders. It would seem either something is fishy, or research science has tripped on itself on dopamine, calling it the reward neurotransmitter and/or the motor function neurotransmitter, or the perception neurotransmitter or the focus neurotransmitter. But that can be said about serotonin as well, in the case of ssri which are being prescribed for so many disorders, besides depression, and tricyclic serotonin reuptake inhibitors are even being prescribed for physical pain8(. I just hoped someone might have known whether dopamine is responsible for reward or motor function, or both and/or more. But I suppose theories are most we have at the moment. But it seems cocaine would have a major impact on parkinsons and pshychosis, by either worsening or improving symptoms if dopamine was their culprit. Imo, what we do know is that dopamine is a culprit in depression given cocaine's ability to increase drive, motivation, alertness and well being, all of which are absent in major depression. Thanks for your input.

• Psychosis is caused by hyperdopaminergia in the brain, in other words, too much dopamine. So no, cocaine would not help with psychosis in fact in would exacerbate it.
• No such thing as a tricyclic SRI. I think you're confusing SSRI's with tricyclic antidepressants or TCA's.

Also, the problem in my opinion is that studies have found that dopamine is strongly correlated to reward seeking behavior, in other words trying to find the stuff you like. The actual act of 'liking' something or the reward may be initiated by a surge of dopamine but might also be coupled with the release of endorphins in natural mechanisms. Hence the confusion IMO.

 

[dimulants]

• Psychosis is caused by hyperdopaminergia in the brain, in other words, too much dopamine. So no, cocaine would not help with psychosis in fact in would exacerbate it.
• No such thing as a tricyclic SRI. I think you're confusing SSRI's with tricyclic antidepressants or TCA's.

Also, the problem in my opinion is that studies have found that dopamine is strongly correlated to reward seeking behavior, in other words trying to find the stuff you like. The actual act of 'liking' something or the reward may be initiated by a surge of dopamine but might also be coupled with the release of endorphins in natural mechanisms. Hence the confusion IMO.

Well, tricyclics also increase norepinephrine, but alongside serotonin. And they were after all replaced by ssri, not complemented.
But to be fair, there are also tricyclics that work on dopamine and the u-opioid receptor, without causing tolerance, all banned in the US. I think France and the rest of the EU aren't that different in terms of views on drug abuse, and wouldn't prescribe them for depression if they were like drugs of abuse. This came up while I was looking up dopamine agonists in search of antidepressant alternatives to ssri/snri. It's like another slap in the face. It's like dopamine is a bad word altogether, again, unless you're obese or have problems focusing (adhd). It would seem that obese overeaters would be more prone to addiction than depressed people simply seeking symptom relief, would bet eating also releases dopamine. Adderall is approved as an appetite suppressant, but not as a suicide prevention med, where it could have been useful as a tool while waiting for antidepressants to kick in. Seems even overeating is more legitimized as a real illness than clinical depression, in that a wider range of medication are available to them. For instance, ssris are also used to treat obesity. So the obese population has all the fda approved antidepressants, plus psycho stimulants available to them, while the clinical depressed by and large only has fda approved antidepressants available, many which have seen research cast serous doubts on their real effeciveness. Seems ssri are also used to treat anorexia, I mean for real. They're used for opposite conditions, all while their mechanism of action isn't proven.
Also, antipsychotics are given for depression, even though they reduce dopamine.


I also think endorphins are clearly implicated in reward, such as feeling good from something. It seems endorphins are also strangely absent form discussions on clinical depression, but are frequently mentioned regarding exercise on mood. I'd say it's not possible to get a runners high with clinical depression symptoms, though. No more than it's possible to enjoy a good meal, as in the reward system being malfunctioning. That's probably why everyone who self medicates seeks out powerful drugs, since regular activities like exercising don't bring sufficient rewards to opt for them instead of the drugs. If low on dopamine, they may not even be able to study and reap those rewards, etc. This problem could have been minimized if there were antidepressants that really worked on dopamine, like stimulants do, but without leading to tolerance. If someone needs a marked dopamine boost to feel ok today, they have no choice but scouring the streets, unless they're lucky to have a good psych doc that prescribes what works. SWIM said he would've scoured the streets already if it wasn't ripe with risks that could jeopardize things he'd worked for, so he's stuck in the limbo of being persistently depressed without being able to find guaranteed meaningful relief. In my personal case it ought to be dopamine, having read how a lack of it can lead to sugar and food cravings, and low motivation, plus having tried Vicodin from a dentist it didn't do much for my mood, thus doesn't seem to be about endorphins here. Maybe it's even that endorphins can't be truly felt without adequate dopamine levels in place. When I tried coke I could more readily imagine pleasure from endorphin releases like from sex, good food, socializing, etc, which normally seem quiet dead.

 

[Euphorogenesis]

Quick heads up, using SWIM is not actually allowed. Also I feel for you, if you suffer from depression. Personally i have had bouts of moderate depression and have basically suffered from low motivation my entire life. However opiates seem to fix this entirely. Which is why i wonder howcome the hydrocodone you got from the dentist didn't work. What was your dosage when trying it if i may ask?

 

[SkyblueMolly]

I personally believe that what really causes depression is mainly under-activated 5HT2a receptors(though serotonin may still play some role). While moderate to severe activation of 5HT2a receptors causes hallucinations, mild activation boosts mood and memory and neuroreceptors alone isn't the cause. IndanylAminoPropane activates norepinephrine, dopamine, and serotonin while mildly activating 5HT2a receptors. It is this combination that produces the most effective anti-depressant effects. Without mild 5HT2a receptors activation, and some activation of other receptors(however mild it may be) we would never develop effective anti-depressants. Mild 5HT2a receptors activation is absolutely necessary for anti-depressant effects. Unless you just want motivation. Stimulants may work by dompamine release, but mild to very mild adrenaline release and sometimes norepinephrine release is needed. Without a mild release(not moderate to extreme) of adrenaline, it may mainly be an empty euphoria. Motivation is likely to come from a release of a combination of receptors in unknown quantity, though dopamine usually plays a large part of the role.
MDxx (ecstasy) releases a much larger amount of norepinephrine, dopamine, and serotonin while mildly activating 5HT2a receptors. Without the mild 5HT2a receptors activation, ecstasy wouldn't be ecstasy.
There are plenty of receptors that are, unfortunately, ignored and under-studied. Mild 5HT2a receptors activation being one of them. Mild 5HT2a receptors activation is also present in 2C-x series at low doses, though moderate to extreme 5HT2a receptors activation is seen in the psychedelic dose range of 2C-x. Mild 5HT2a receptors activation combined with neuroreceptors produce anywhere from memory enhancement and increased problem solving skills to increased mood and energy, to decreased anxiety, depending on the 2C-x(2C-D, 2C-I, 2C-C, ect.). I assume the expansion of the 2C-x series may lead to the next NZT. The receptors and their interactions and the levels of activation is still complicated though.

 

[catfishjake]

Great thread

 

[Rybee]

I've always wondered why Dopamine Re-uptake Inhibitors were not more widely used for the treatment of depression.

 

[St3ve]

I personally believe that what really causes depression is mainly under-activated 5HT2a receptors(though serotonin may still play some role). While moderate to severe activation of 5HT2a receptors causes hallucinations, mild activation boosts mood and memory and neuroreceptors alone isn't the cause. IndanylAminoPropane activates norepinephrine, dopamine, and serotonin while mildly activating 5HT2a receptors. It is this combination that produces the most effective anti-depressant effects. Without mild 5HT2a receptors activation, and some activation of other receptors(however mild it may be) we would never develop effective anti-depressants. Mild 5HT2a receptors activation is absolutely necessary for anti-depressant effects. Unless you just want motivation. Stimulants may work by dompamine release, but mild to very mild adrenaline release and sometimes norepinephrine release is needed. Without a mild release(not moderate to extreme) of adrenaline, it may mainly be an empty euphoria. Motivation is likely to come from a release of a combination of receptors in unknown quantity, though dopamine usually plays a large part of the role.
MDxx (ecstasy) releases a much larger amount of norepinephrine, dopamine, and serotonin while mildly activating 5HT2a receptors. Without the mild 5HT2a receptors activation, ecstasy wouldn't be ecstasy.
There are plenty of receptors that are, unfortunately, ignored and under-studied. Mild 5HT2a receptors activation being one of them. Mild 5HT2a receptors activation is also present in 2C-x series at low doses, though moderate to extreme 5HT2a receptors activation is seen in the psychedelic dose range of 2C-x. Mild 5HT2a receptors activation combined with neuroreceptors produce anywhere from memory enhancement and increased problem solving skills to increased mood and energy, to decreased anxiety, depending on the 2C-x(2C-D, 2C-I, 2C-C, ect.). I assume the expansion of the 2C-x series may lead to the next NZT. The receptors and their interactions and the levels of activation is still complicated though.

I don't think your hypothesis is valid... Mirtazapine, which is effective in more patients than SSRIs, is a pretty potent antagonist of 5ht2a. If anything it seems like 5ht2a inactivation would then cause antidepressant effect.

MDMA might be weak agonist at 5ht1 and 5ht2 receptors, it's also a potent as fuck releaser. With the brain so filled up with free floating serotonin, all serotonin receptors will be getting activated plenty.