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New Study In Mice Shows That Increasing Serotonin Affects Motivation, But Only In Certain Circumstances (neurosciencenews.com)

New submitter baalcat quotes a report from Neuroscience News: A new study in mice shows that increasing serotonin, one of the major mediators of brain communication, affects motivation -- but only in certain circumstances. Furthermore, the study revealed that the short and long term effects of increased serotonin levels are opposed -- a completely unforeseen property of this neurotransmitter's functional system. A surprising behavioral effect, discovered in mice by neuroscientists at the Champalimaud Centre for the Unknown (CCU), in Lisbon, Portugal, strongly suggests that serotonin is involved in a biological mechanism which affects the animals' motivation. The study has now been published in the online open access journal eLife. Serotonin, one of the chemical "messengers," or neurotransmitters, in the brain, is used by neurons to communicate with each other. It plays an important role in the regulation of sleep, movement and other behaviors which are essential for animal survival. But for motivation in particular, it was unclear whether serotonin was involved. Using optogenetics, the team stimulated the release of serotonin from neurons in the raphe nuclei. They first induced "peaks" of serotonin by stimulating these neurons with pulses of light, lasting three seconds every ten seconds, over three five-minute time periods. The mice, placed in a box, were left free to explore their environment. In these conditions, their most frequent spontaneous behaviors are walking around, rearing, grooming, digging holes or keeping relatively still, but nevertheless alert. The only difference the scientists saw was that stimulation caused the mice to reduce their locomotive speed by about 50%. In general, this stimulation of serotonin-producing neurons did not affect other behaviors. The effect of these serotonin "peaks" on locomotion was almost instantaneous (speed reduction manifested one second after stimulation) and transient, with things going back to normal after five seconds. But during this short period of time, "the animals acted as if they weren't motivated," says Zach Mainen, who led the study.

47 comments

  1. First by Anonymous Coward · · Score: 0

    Boy, this increased serotonin level really does motivate me!

    1. Re:First by Anonymous Coward · · Score: 1

      You're a mouse?

    2. Re: First by Anonymous Coward · · Score: 0

      Works best with Razer and Logitech mice, not so good with Kensington.

  2. SSRIs by Anonymous Coward · · Score: 2, Interesting

    As someone who's seen SSRI's "work" on people you most find that they lose what they want to do. For some people want they want is unachieveable, but when someone else wants to be a functional person and instead sits around all day and ends up not wanting to get better, that's not an improvement even if they feel better.

    It'd be interesting to see them continue this in the face of challenges, like shock floors or social situations.

    1. Re:SSRIs by Puff_Of_Hot_Air · · Score: 5, Informative

      As someone who's seen SSRI's "work" on people you most find that they lose what they want to do. For some people want they want is unachieveable, but when someone else wants to be a functional person and instead sits around all day and ends up not wanting to get better, that's not an improvement even if they feel better. It'd be interesting to see them continue this in the face of challenges, like shock floors or social situations.

      Which is exactly what they did and you clearly didn't read the article.

      “But the same stimulation does not have any effect if the animal is already engaged in a specific task such as running to get a reward”

      The decreased motivation (physical movement speed) was only temporary. The study showed that over a longer period of increased Serotonin, locomotion speed was up by 30%-40% from starting levels; the researches are looking at this as an explanation as to why SSRI drugs take about 3 weeks to start working.

    2. Re:SSRIs by Anonymous Coward · · Score: 0

      That's idiotic... the symptom you describe is one of the most common indicators of depression, which is why SSRI's are prescribed in the first place.

      I'm not going to defend them - I think they are one of the greatest ills of today's society - but you're kind of stretching to find a cause after the effect.

    3. Re:SSRIs by Anonymous Coward · · Score: 1

      SSRIs also really fucked up sleep. You're tired all the time and can't concentrate.

      Medication like that should be only used for folks who are clinically depressed anyway - think Gilbert Grape's mom (What's Eating Gilbert Grape). For dysthymia the best thing I found was aerobic exercise. Swimming and running worked much better than anti-depressants, REBT, CBT, Mindsight and every other talk therapy.

    4. Re:SSRIs by Anonymous Coward · · Score: 0

      A lot of the effect of SSRIs is probably placebo effect. There's a mismatch of many orders of magnitude with regard to the time scale of when the SSRIs increase serotonin concentrations in the brain versus when a person starts to feel better. This makes it very difficult to distinguish spontaneous recovery from effects of the SSRI.

      However, let's say that SSRIs actually have a pharmacological effect. In particular, let's assume that they make people more motivated. Well, that's might be a good thing if a person just needs a little kick to go out and find a new job after a nasty layoff. But it might be a very bad thing if the person wants more than anything to not exist - that is, if they're suicidal then the SSRI might provide the motivation to kill themselves.

      Some people swear by SSRIs so I'm not saying they're all bad. But it's definitely a more nuanced picture than what you might get from watching the SSRI commercials on TV back in the day.

    5. Re:SSRIs by Fragnet · · Score: 1

      What makes you think they aren't used on people who're clinically depressed? I've taken them for years, on and off. I am currently on my second week of taking them (again). And just try to get any other kind of treatment in the UK. REBT, CBT, Mindsight? Goodness me. It would either be a great personal expense or an 18 month waiting list (in the UK I mean).

    6. Re:SSRIs by Fragnet · · Score: 1

      if they're suicidal then the SSRI might provide the motivation to kill themselves

      There's definitely a placebo effect, simply from going to see someone and have them listen to you and appear to care about your illness. It's often impossible to discuss with anyone else other than a GP. I always feel better after having done that before I take the medication. However that does not stop the suicide ideation - the thought that pops into your head every 5 minutes. Taking the SSRI reduces it.

    7. Re:SSRIs by dunkelfalke · · Score: 4, Interesting

      It is an improvement. Given the choice of sitting around all day and feeling like shit or sitting around all day and feeling okay, I'd always go for the latter.
      I lost motivation years before starting taking SSRI.

      --
      "It's such a fine line between stupid and clever" -- David St. Hubbins, Spinal Tap
    8. Re:SSRIs by Anonymous Coward · · Score: 1

      That isn't true. There is a long time between when you start taking SSRIs and you start "feeling better" as it takes a while for the drug to build up in your system to increase the uptake. In fact during that period you might feel a lot worse. Any psychologist warns you of this. SSRIs definitely work. They don't "motivate" you. They are used to treat depression.

    9. Re:SSRIs by Anonymous Coward · · Score: 0

      CBT and talk therapy can be done free online. Go buy some books on the subject or check them out from your local library. You don't even need to read them, get the audio book versions. Studies show these treatments are just as effective as meds if not better, so you owe it to yourself to try them as they're far cheaper and provide no negative side effects. Plus they help you manage stress in your daily life too.

    10. Re:SSRIs by Billly+Gates · · Score: 1

      Well from personal experience I backup grandparent. Yes myself is not valid scientific B's yada yada.

      I got fired from a job the first time I tried SSRIs when I was younger. I came in late and knew I was supposed to be at work but laid in bed going meh. I was mad at myself for years thinking I was immature and deserved it in which I did.

      I never got connection. I tried SSRIs again recently. Low and behold within a few days I quit studying for my certifications, my apartment became messy, and had a verbal warning about coming into work on time. I even stopped watching TV and just slept in all weekend all in peace. I stopped them with all the brain zaps and shocks that come from stopping all of the sudden. I had to be responsible.

      Within 48 hours I was back to normal. Who cares about rats speeds? The real effects are like going hungry. Serotonin and dopamine are linked to rewards. If you always feel full the urge to eat goes down. The brain has enough neurotransmitters it won't go thru the effort for work or pleasure

    11. Re:SSRIs by Billly+Gates · · Score: 1

      Oddly for me a half child's dose helped as I rested more at night with REM. I finally had the energy during the day

    12. Re:SSRIs by Anonymous Coward · · Score: 0

      Totally can confirm this (also anecdotally, etc. etc.)

      Unfortunately, SSRIs are a necessary part of my healthcare. Otherwise I would gladly stop taking them -- I know my motivation is far below what it was before starting them. And that's while I absolutely love what I do for work. I tend to procrastinate significantly more, I'm less motivated to do stuff on weekends, and I would love to sleep until 2pm (despite going to bed at a reasonable hour).

      For now, I'm stuck with them.

    13. Re:SSRIs by Billly+Gates · · Score: 1

      Don't take them.

      2 months clean and part of my super negative thought cycles are now gone. They are somewhat back but manageable. SSRI s permanently change brain structure. They stop working after several years and can permanently ruin your sex drive the longer you are on them.

      SSRIs work for just several months repairing damage but can cause other damage

    14. Re:SSRIs by Anonymous Coward · · Score: 0

      There is a long time between when you start taking SSRIs and you start "feeling better" as it takes a while for the drug to build up in your system to increase the uptake.

      No, the SSRIs cross the blood brain barrier on a time scale of minutes and inhibit the re-uptake of serotonin leading to a massive spike of serotonin levels on a time scale of hours. But the claimed effect (depression cured) takes place on a time scale of weeks or even months.

      If the treatment and cure have a strong correlation then, even if the treatment is a complete "black box", it's still possible to be confident that the treatment is working. But in this case the correlation between treatment and cure is so weak that it's difficult to make a definitive conclusion.

      SSRIs definitely work.

      There are lots of different definitions of "work" - feel more hopeful, don't commit suicide, etc. But, regardless of the definition, they don't "work" all the time. And, even when they do work, a key question is how much is pharmacological and how much is placebo.

      They don't "motivate" you. They are used to treat depression.

      Depression is a broad range of feelings emotions including sadness, guilt, despair, hopelessness, and lack of motivation.

      Obviously there are drugs that cause powerful positive feelings: valium, crack cocaine, meth, etc. Some of these drugs even make a person feel more motivated - like superman - that anything is possible and nothing can go wrong. But the pharmacological effect of these drugs also closely correlates with their concentration in the brain. You take the drug, it goes to the brain, you feel the effect, and then as the drug is cleared from your system, the effect goes away.

      With the SSRIs, though, the dosage/effect correlation is much weaker.

    15. Re:SSRIs by Puff_Of_Hot_Air · · Score: 1

      No, the SSRIs cross the blood brain barrier on a time scale of minutes and inhibit the re-uptake of serotonin leading to a massive spike of serotonin levels on a time scale of hours. But the claimed effect (depression cured) takes place on a time scale of weeks or even months.

      Which is why this study is so interesting. It essentially replicated this exact effect. The mice had decreased motivation (locomotion speed) after directly tinkering the serotonin up, but over a longer time scale they had increased locomotion from their base levels. Essentially replicating the human experience, and providing a much more direct way to study the effects of this particular chemical. This is interesting science as we still have very little understanding about Serotonin.

    16. Re:SSRIs by N_Piper · · Score: 1

      Yes and some people just want to not be contemplating suicide 24/7.
      I've been on SSRI's for most of their commercial existence, I NEED them, I've seen the other side some nitwits had my father doped up so high that he nearly died of serotonin poisoning.
      Yes, too much serotonin causes an "everything is fine" lethargy, I've been there, but if the starting dose causes that it means you have a normal brain chemistry and were sad because things sucked.

    17. Re:SSRIs by Anonymous Coward · · Score: 0

      The effect of increasing energy/motivation is already known, which is one reason SSRI's have warning labels on them about suicide and depression. You can be so far depressed that you don't have the energy to follow through on a suicide plan (I've been that depressed). While anti-depressants start to work you'll gain more energy before the anti-depressant feeling so the risk of carrying out a suicide plan at that point is real. That's one reason you're supposed to stay in close contact with your doctor when you start taking them.

      The other reason for the warnings is because taking SSRIs when you aren't depressed actually causes you to become depressed. If you look into that a little closer, it completely blows apart the industry's narrative that depression is caused by low serotonin (which is why they like to pretend SSRIs have no withdraw effects). It also strengths the arguments that SSRIs are causing brain damage and the tolerance people gain to their meds is the brain damaging itself to avoid the unnaturally high serotonin levels. With more serotonin sticking around the brain cuts serotonin production to keep levels at what it thinks normal should be. However the serotonin floating around is past it's life time and is degrading (SSRIs stop it from being recycled). The degraded molecules damage the serotonin receptors which eventually results in the original situation. You end up with the brain thinking it has a ton of serotonin available but the brain isn't able to use any of that serotonin. When you stop taking SSRIs, the brain is still in lowered serotonin production mode so your usable serotonin completely drops even further, thus leading people to wrongly believe they're still depressed. In actually, they've become dependent on their meds and the thing which caused the initial depression may or may not have been resolved years ago. For non-depressed people who take SSRIs, the process happens quicker since they already had higher levels of serotonin and their first pills are putting their brain out of whack.

      When was the last time you had your serotonin levels checked before starting a SSRI? Never. The only way to check them is through a brain dissection and we don't dissect depressed people who don't use SSRIs because they never come in complaining about depression. The whole industry surrounding depression is flawed. Our theory of depression came from dissecting people who died after being on SSRIs (before we called them SSRIs). Researchers saw these people had higher serotonin levels and concluded that since SSRIs increase serotonin and since SSRIs help with depression, then depression must be caused by low serotonin levels.

      Go look at the independently published studies and meta-studies. SSRIs are only slightly better than chance. Many SSRI studies don't show benefits beyond placebos and the non-medication treatments perform better. At the least, none of the non-SSRI treatments give you depression.

      Basically, my point is improper serotonin levels is a symptom, not a cause. You don't fix things by treating the symptoms and leaving the cause in place. Instead of turning to SSRIs to treat your symptoms, turn to something else and actually fix your depression. It takes more work, but the result and financial savings are super worth it.

    18. Re: SSRIs by Anonymous Coward · · Score: 0

      Have you tried dopamine based medication, they often work much better including depression.

    19. Re:SSRIs by Anonymous Coward · · Score: 0

      I had a half-minimal dose of an SSRI and it gave me a 2 hour adrenaline rush. My doctor said to never take one again, it could kill me.

  3. Bright light by Anonymous Coward · · Score: 0

    I'd probably behave the same way if someone was shining a bright light in my face every 10 seconds:

    >> speed reduction manifested one second after stimulation and transient, with things going back to normal after five seconds. But during this short period of time, "the animals acted as if they weren't motivated,"

  4. Maybe by kackle · · Score: 4, Insightful

    Being the effect was temporary, could it be they just felt "sick" or stunned? A general brain fog?

    1. Re:Maybe by budgenator · · Score: 1

      When I both started and stopped taking an SSRI there were prolonged periods where I was dizzy when turning while walking and shorter periods while driving. There were even a few instances of depersonalization and derealization, so when you feel like you're trippin', you tend to move slowly ans deliberately.

      --
      Apocalypse Cancelled, Sorry, No Ticket Refunds
  5. There are human examples by TimothyHollins · · Score: 1, Interesting

    Isn't this the same effects we see in drug addicts (of downer drugs obv.) ? An almost immediate reduction in activity as contentment sets in.
    At least I haven't seen an "active" potsmoker.

    I wonder if the long-term effects would be the same for humans and mice as well.

    1. Re: There are human examples by Zero__Kelvin · · Score: 0

      On the contrary you have seen many, many, many active marijuana smoker's. You just had no idea they were weed smoker's. Did you think they would wear a sign?

      --
      Guns don't kill people; Physics kills people! - John Lithgow as Dick Solomon on Third Rock From The Sun
    2. Re:There are human examples by swb · · Score: 4, Interesting

      I think it really depends on the people. I know a lot of pot smokers who do otherwise repetitive, dull tasks while stoned but when not stoned they start them and then are distracted by something and never finish the tasks. For them being stoned seems to allow them to have a kind of hypnotic focus on the task at hand. My sense is their high level conscious mind goes elsewhere, while their low-level conscious mind can just robotically perform the task in front of them.

      I think this has probably been true and associated with a lot of populations tied to repetitive tasks like agricultural field work.

      Overall I think it's highly specific to the drug in question and to the people in question. With pot in particular people may have a learned behavior associated with "getting stoned" -- it's not just the drug effect, but an entire drug use ritual or process which probably starts with abandoning constructive activity to begin with and following the drug use with pleasurable activity -- TV or video games or something else.

      There was a great article a few years ago about a woman who had a lobectomy for epilepsy that cured the epilepsy by that resulted in a lack of short term memory. After her injury, she went from being a merely good distance runner into a phenomenal ultra-marathoner, and they attribute her stamina partly to her short term memory problems. She doesn't have the kind of short-term distractions and mental fatigue that can plague other people.

      Anyway, I think a similar phenomenon happens with some pot smokers -- they lose partial awareness of what they're doing and for some it makes dull, repetitive tasks easier. Obviously tasks involving complex thinking might be more difficult and associated behaviors with pot smoking may interfere with even simple tasks for others.

    3. Re:There are human examples by boristdog · · Score: 2

      Fairly accurate.

      When I have some seriously repetitive or physically difficult task that I am avoiding (washing dishes, cleaning house, putting in fence posts, shoveling rocks or dirt, mixing concrete, etc.) weed gives me the motivation to do it and the stamina to finish it. (I live on a farm)

      Anything involving dangerous equipment or serious thinking (chainsawing, taxes, writing reports, etc.) and I definitely do NOT hit the pipe first.

      YMMV.

  6. Motivation by zifn4b · · Score: 1

    Businesses are trying to figure out how to make employees more motivated. The answer is: ignorance. An operant conditioning box (aka Skinner Box) only works so long as the subject is unaware of the box. The only thing that truly motivates anyone is self interest and a belief that their efforts can achieve it. Once the person has lost the ability to believe they can achieve whatever they put their mind to, motivation plummets to 0. In America, the problem is too many "game theory" players have tricked people using psychology into believing that what they are doing has some meaning to them aka incentivization. In reality, it's all about getting someone to do something for someone else's gain and in many cases to the detriment of the person exerting the actual effort.

    --
    We'll make great pets
    1. Re:Motivation by swb · · Score: 1

      And in many cases, they are shattering the long-term motivation by reneging on the essential bargain people believed they had.

      Work hard, go to college, get a good job, and enjoy material prosperity and happiness.

      Years ago we began sabotaging the material prosperity angle, we're killing off the good jobs which also kills off the going to college. You're left with working hard for no possible gain.

      We're segueing back into a slave labor economy where mere survivalism is the sole remaining motivation and that won't work well for anyone.

    2. Re:Motivation by Anonymous Coward · · Score: 0

      Work Hard --> Prosperity, even luxury
      Collapsed to "work hard, maybe"
      Collapsed to "work hard, get by"
      Collapsed to "work hard, or else someone waiting outside HR gets your musical chair"

      Can't wait to see what's next for the commoner class.

    3. Re:Motivation by zifn4b · · Score: 1

      And in many cases, they are shattering the long-term motivation by reneging on the essential bargain people believed they had.

      Work hard, go to college, get a good job, and enjoy material prosperity and happiness.

      This was covered quite well by Mr. Alan Watts in his talk Life is a Hoax. He was very much ahead of his time. When you realize these things, you truly do become free at least in the sense of being a free thinker.

      --
      We'll make great pets
    4. Re:Motivation by swb · · Score: 1

      I mean obviously, our larger social structure has a false quality to it, but really any civilization beyond subsistence agriculture does because of the structural aspects required to make it work. A lot of this just boils down to the demands associated with economics and economic specialization.

      But at a certain point, though, the "rules of the game" have to kind of work to maintain the structure and order of the system. If it doesn't follow the rules, the system will break down.

    5. Re:Motivation by zifn4b · · Score: 1

      I mean obviously, our larger social structure has a false quality to it, but really any civilization beyond subsistence agriculture does because of the structural aspects required to make it work. A lot of this just boils down to the demands associated with economics and economic specialization.

      But at a certain point, though, the "rules of the game" have to kind of work to maintain the structure and order of the system. If it doesn't follow the rules, the system will break down.

      Ultimately what is the point of the system? We seem to have gone well beyond the 1st tier of Maslow's Hierarchy of Needs. At what point should the system support the other tiers?

      --
      We'll make great pets
    6. Re:Motivation by swb · · Score: 1

      I'd say "civilization", but really that question should have been asked about 10,000 years ago when people stopped roaming around and killing things for food and instead decided that the surpluses of sedentary agriculture were more valuable.

      Once we got food surpluses, we had people with nothing to do, casting about for a purpose in life.

      It all kind of reminds me of one of my favorite quotes -- "Civilization is the hopeless race to discover remedies for the evils it creates."

      Or you can just take an existentialist position and say there is no point. To do is to be.

  7. I take SSRI's; motivation is fine by scourfish · · Score: 1

    I understand where the article is coming from, though. Several years ago, I was prescribed an SSRI for anxiety and depression. The first two weeks of taking it made me feel out of myself, like I was a zombie. It wasn't a buzz, it wasn't a fog, it was just this feeling of depersonalization. The first few weeks could be viewed as "demotivating" because I just really didn't care about much in my zombie like state. Everything was dulled. Over the course of those two weeks, this dullness started lifting and I felt like myself again. It took a few more months to adjust completely. Now, I would say my motivation is better than before, because a blanket that made me doubt myself constantly has been lifted.

    1. Re:I take SSRI's; motivation is fine by Anonymous Coward · · Score: 0

      I agree and had a similar experience. The first few weeks actually made me feel way worse depression-wise, but once it cleared up I was able to get back into my normal routine and catch up on the things I had let slide in the intervening weeks. As a side effect it made me realize that I had been suffering from anxiety my whole life and never known it, because all of a sudden as the depression lifted I wasn't worried about every little thing anymore. The doctor let me stay on them for my anxiety and it definitely improved my overall motivation and quality of life.

    2. Re:I take SSRI's; motivation is fine by dunkelfalke · · Score: 1

      My first weeks were somewhat different - untypically good mood, often giggling about trivial stuff and telling stupid jokes to my coworkers, but not caring much about anything at all. I guess this is how dope smokers feel like when they are high.
      It was fun while it lasted.

      --
      "It's such a fine line between stupid and clever" -- David St. Hubbins, Spinal Tap
    3. Re:I take SSRI's; motivation is fine by Billly+Gates · · Score: 1

      For me with ADHD it made things worse.

      I almost was fired as I didn't even care if I was late for work. I had to stop taking them as a result. It makes sense as if I feel fine why bother with work and self improvement?

  8. Could it be.. by OneoFamillion · · Score: 1

    So at first the mice chillax, aka get the "hey, maybe this isn't so serious after all" feeling, but their reduced feelings of unease allow them to be more relaxed and healthier = more productive in the long run?

  9. Re:No negative side effects by hackwrench · · Score: 1

    Citation needed

  10. You don't understand depression by hackwrench · · Score: 1

    There is depression where the primary symptom is suicidal feelings and there is depression where the primary symptom is lack of motivation and anywhere in between. Right now, I am struggling with lack of motivation.

  11. brave new world coming by Anonymous Coward · · Score: 0

    So, can your employer require that you take a pill every day as a condition of employment? Or maybe require that you drink coffee?

  12. seretonin's many dominoes by epine · · Score: 1

    For myself, negative ideation (which for me is not suicidal, just an endless litany of everything I've ever done wrong in front of another person) strongly correlates with sleep quality.

    As soon as I reach the threshold where the negative thoughts are disruptive to daily life, I take of several effective sleep medications, and—if I manage to get the hard and deep sleep I need—negative ideation is gone again the next day.

    Hours in the sack don't count, either. I've had times where I've been getting a solid eight hours of consolidated sleep for an entire week, but still the negative ideation has made an appearance. Sometimes my sleep seems to hollow out so that it's non-restorative on some hidden, inner dimension.

    At present, my best sleep-quality aid is 3–4 mg of nortriptyline, a dosage I have custom-compounded at a local compounding pharmacy.

    Its off-label uses include treatment of chronic fatigue syndrome, chronic pain and migraine, and labile affect in some neurological disorders.

    Fewer and milder side effects occur with nortriptyline than tertiary tricyclic antidepressants such as imipramine and amitriptyline.

    I was originally prescribed amitriptyline, which also worked great to restore my sleep quality, but left me fuzzy-headed the next day.

    The later substitution with nortriptyline was based on my own research effort, as was carefully titrating my minimal therapeutic dose (which ends up costing me six times than as much as the minimum standard dose of 10 mg, available in capsule form only—what's less fuzz in the brain the morning after worth to you?)

    If I really need to drop the sleep hammer, I take two, then write off part of the next morning to light housework.

  13. How about studying humans by p51d007 · · Score: 1

    I could care less how this or that makes mice into super mice... How about studying humans? (yes I know why they do the studies on mice)