Social defeat and how to overcome it: 7,8-Dihydroxyflavone and BDNF
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Very interesting study.
The first thing it establishes is that high novelty-seeking rats (HR) are more susceptible to social defeat stress and resulting depression than low novelty-seeking rats (LR). This surprises me since novelty exposes you to more unpredictability and more social defeat opportunities.
Here’s the catch: the social defeat was dependent on hippocampal BDNF levels. HR rats experienced a decrease in BDNF after social defeat, while LR rats experienced an increase in it.
Now you might wonder: can a socially defeated and avoidant rat become social again by altering BDNF?
The answer seems to be yes! Blocking hippocampal BDNF led to social avoidance, while increasing it via 7,8-Dihydroxyflavone led to social approach.
7,8-Dihydroxyflavone is a supplement for sale, which potently increases BDNF. (It’s available at Nootropics Depot.)
As we know, serotonin is associated with social defeat, so you could expect that 7,8-Dihydroxyflavone decreases it. And indeed, I found a study showing that 7,8-DHF decreases hippocampal serotonin at a Human Equivalent Dose (HED) of 30 mg. Usual dosing schedules that I saw ranged from 10–50 mg, so this concentration should be achievable, especially using sublingual administration.
"Administration of the low drug dose (2.5 mg/kg) had no effect on any of the study parameters, while administration of the high drug dose (5 mg/kg) decreased cortex and hippocampus levels of serotonin and its major metabolite, 5-hydroxyindoleacetic acid..."
https://link.springer.com/article/10.1007/s11055-019-00786-0Original study: https://pubmed.ncbi.nlm.nih.gov/23825410/
Dare to think.
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@Mauritio said in Social defeat and how to overcome it: 7,8-Dihydroxyflavoneand BDNF:
The first thing it establishes is that high novelty-seeking rats (HR) are more susceptible to social defeat stress and resulting depression than low novelty-seeking rats (LR). This surprises me since novelty exposes you to more unpredictability and more social defeat opportunities.
As I suspected the increase in BDNF might be apaptational. So maybe the increased novelty seeking is a result of increased BDNF in response to the stress. This study is clear that this adaptation weakens in adulthood ,suggesting that it might have to do with lowered neurosteroid production as for example progesterone increases BDNF.
"Preclinical and clinical data suggest early-life social adversities (ELSA) might be associated with accelerated maturation of social network circuitry, a possible ontogenic adaptation to the adverse environment. Neural plasticity decreases by adulthood, lessening the efficacy of treatment in ELSA-related psychiatric disorders. However, literature data suggest that by increasing BDNF/TrkB signalling through antidepressant treatment a juvenile-like plasticity state can be induced, which allows for reorganization of the social circuitry when guided by psychotherapy and surrounded by a safe and positive environment."
https://pubmed.ncbi.nlm.nih.gov/30341412/So the chronological order could be as follows :
(Early) life stress- → adaptive increase in BDNF→ increased novelty seekingCerebellar BDNF Promotes Exploration and Seeking for Novelty
https://pubmed.ncbi.nlm.nih.gov/29471437/ -
@Mauritio
I had read about the enhanced neuroplasticity from high BDNF long ago and since then thought more BDNF would be a good thing. Pretty much like your first post above suggests.Yet then there's something like too much BDNF and it appears to be related to increased estrogen receptor activation and serotonin levels (see study below).
And the context outlined in your second post seems much more crucial:@Mauritio said:
So the chronological order could be as follows :
(Early) life stress- → adaptive increase in BDNF→ increased novelty seekingAnd I regard this bold part as crucial:
@Mauritio said:by increasing BDNF/TrkB signalling through antidepressant treatment a juvenile-like plasticity state can be induced, which allows for reorganization of the social circuitry when guided by psychotherapy and surrounded by a safe and positive environment."
because all that increased novelty seeking and curiousity induced by early life stress, exposing you to more unpredictability and more social defeat opportunities
fits very well into the pattern of such people trying to socialize and reach out and befriend others to their own detriment and falling deeper and deeper the more they try. And in this way, continously attract additional damage to themselves.*
Whereas the uninvolved would tackle such situations and strangers much more indifferently, carefully or adversarially and be therefore better off.*The probability and frequency of making a potential lifetime friend who's just as early life damaged and uniquely resonating with oneself, overall, is really poor.
Estrogen and serotonin enhance stress-induced visceral hypersensitivity in female rats by up-regulating brain-derived neurotrophic factor in spinal cord
We previously reported that female offspring of dams subjected to chronic prenatal stress (CPS) develop enhanced visceral hypersensitivity (VHS) following exposure to chronic stress in adult life that is mediated by up-regulation of spinal cord BDNF.
Ovariectomy before CAS [chronic adult stress] or treatment with letrozole before and during CAS significantly prevented the development of enhanced VHS in female CPS+CAS rats.Intrathecal application of ERα siRNA significantly reduced VHS, decreased lumbar-sacral spinal cord expression of both ERα and BDNF, and reversed pro-transcriptional epigenetic modifications at BDNF promoter lX.
Cerebrospinal fluid serotonin levels and 5HT3A receptor expression in the LS spinal cord were both significantly increased in female CPS+CAS rats.
During CAS, intrathecal infusion of alosetron significantly decreased VHS, reduced BDNF and ERα expression in the LS spinal cord, and attenuated RNA pol II and ERα binding to the BNDF core promoter IX.
Instead of using anti-serotonins (which are very limited, really) or pro-dopamines, this shows up the possibility of using aromatase inhibitors to achieve the former through lowering estrogens as a new angle to approach.
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@CrumblingCookie Of course there is such a thing as too much BDNF, but you can say that about anything. l regard increasing BDNF as something positive hence why progesterone increases it.
It seems that Estrogen and serotonin increase BDNF but that doesn't mean BDNF increases estrogen and serotonin. Otherwise it would be unlikely that 7, 8 DHF lowers Serotonin -
@Mauritio Thanks, but I might be too CAS myself rn to wrap my head around this. So the increased BDNF from (early) life stress is a reactive marker? And would serotonin be even higher if it weren't for the (initially) reactive increase in BDNF? Put more narratively: Is the increase in BDNF as a response to (early) life stress an effort of an escape mechanism, by increasing neuroplasticity to curiously find out better ways to cope with the environments?
And then practically, and paraphrasing the quote above, if we were to take 7,8-Dihydroxyflavone to raise BDNF again: Would that merely further entrench and enhance the previously adopted early life stress when in lack of opportunities or an overall positive and safe environment or at least situational and strategic awareness with distinctive goals?
So essentially proper self-flagellation without the latter beneficial/productive prerequisites? -
@CrumblingCookie said in Social defeat and how to overcome it: 7,8-Dihydroxyflavone and BDNF:
And would serotonin be even higher if it weren't for the (initially) reactive increase in BDNF?
I don't know. This thread is more about 718-DHF, which seems to lower serotonin is higher doses.
@CrumblingCookie said in Social defeat and how to overcome it: 7,8-Dihydroxyflavone and BDNF:
Is the increase in BDNF as a response to (early) life stress an effort of an escape mechanism, by increasing neuroplasticity to curiously find out better ways to cope with the environments?
Yes, I think so. Maybe that's why both progesterone + Estrogen increase BDNF .E increases it as a survival mechanism and maybe prog as a reactionto a stimulating environment.
@CrumblingCookie said in Social defeat and how to overcome it: 7,8-Dihydroxyflavone and BDNF:
Would that merely further entrench and enhance the previously adopted early life stress when in lack of opportunities or an overall positive and safe environment or at least situational and strategic awareness with distinctive goals?
I don't think so. This study shows that BDNF makes you more resilient.
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This study shows 7, 8-DHF is an aromatase inhibitor. Although in-vitro so take it with a grain of salt, but still positive.
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@Mauritio
Interesting. From what I could scan it appears 7,8-Dihydroxyflavone lowers overall estrogen levels whilst upregulating quantity and (ligand-independent) activation of estrogen receptors.
What are any natural dietary sources for 7,8-Dihydroxyflavone?
Are you going to take it? -
@CrumblingCookie I already took it and it definitely increased my mental capacity and was stimulating to the brain as well.
