79 replies to this topic

[Autumn Knight]

 

 

Also, does upregulation mean heal? 

People always say that but it doesn't mean much to me right now.. 

 

 

What sort of disorder do you have..? At your baseline. Which drives you to do such amounts of MDMA? Seriously - everyone I've ever heard of who does that, have SERIOUS OTHER ISSUES, which they try to self-medicate.

 

So what ails you, friend? Your ORIGINAL problem, that is.

 

The only thing I can suggest with all of your acquired problems are neurogenics: Dihexa, NSI-189, and some other compounds which my burnt-out mind can't recall at this time.

 

They are all untested and the long-term effects are unknown - several of them, are perceived to be not harmful, but there is little data. Sadly, it's the only thing my own burnt-out brain can think of which would actually help - you've bathed your brain in actual neurotoxins, physically destroying parts of it.

 

The only way to get a true recovery is to make your brain actually regrow damaged parts. It can be done, but it's not for the faint of heart.

 

 

Regarding UPREGULATION:

 

It means to restore receptors, or to increase density of receptors. In a way it can be a healing, if you have damaged your receptors. It can also mean that your receptors are not so much damaged, as in a dormant state, shut down by your body to prevent further damage. (temporarily downregulated. this is often the case with people gaining tolerance to amphetamine - a feedback mechanism notices that amphetamine is altering the balance in your brain, and hence orders your brain to turn off x amount of dopamine-receptors, to decrease the effects of dopamine. often this decrease is greater than necessary - the brain is over-zealous in correcting things)

 

 

I quit 8 years ago. 

I didn't have an original problem. MDMA makes anyone feel happier, even if they're fine. I guess I just liked that. 

I have Dihexa on order; it should be here in about a week. I'm currently arranging to order NSI, although I won't take both at once. A testimonial is planned for each, which I will post here. 

Well, how do you do it? It has gotten better over time, but still working at it. Ah, okay, thanks.  

[Autumn Knight]

 

such a homopathic way of you viewing some herb as a simple "weak" agonist. it has myriad of unwanted side effects why dont you homopaths ever cite those together with the supposedly "good reactions"

Come now normalising, don't be so prejudiced! Apply some critical thinking to what people are suggesting too! Trollness aside, you could improve your manor (which might improve once you resolve your D2 issues I reckon)

Have you been able to differentiate what type of dopamine receptor you need to focus on? There exists D2(SHORT) and D2(LONG)

D2 receptors have autoreceptors which function to decrease dopamine synthesis / neuron activity...two distinct pathways, but the autoreceptors are ONLY the pre-synaptic ones (D2s), whereas D2 L = D-2-"Long" has it's post-synaptic effects and a stronger downstream effect more indicative of a dopaminergic pathway and having more interaction with the D1-like receptors...

Forskolin only unregulates D2L I think.

There's also bromantane, sulbutiamine, 9 mebc for dopamine upregulation.

Another user suggested:

tianeptine and phenyl piracetam together with inositol / CDP-Choline should result in a 7-fold increase in dopamine D2 receptor concentration abroad.

YMMV.

Try this thread for more info on increasing D2:
http://www.longecity...on-and-related/

@Autumn Knight
MDMA will downregulate VMAT which is the principle thing that loads neurotransmitters and prepares them for firing. (It takes neurotransmitters from the cytosol and loads them into vesicles ready to be fired into the synapse)

Less VMAT = highly undesirable.

Mesembrine from kanna has been shown to upregulate VMAT, though the action is unknown.

 

"MDMA will downregulate VMAT"

Where did you learn that? 

[sativa]

Uridine and N-Acetyl-Cysteine would be ideal for dopamine system upregulation aka increase dopamine receptor count/density.

Jiaogulan (Gynostemma pentaphyllum) Has a restorative effect on dopaminergic systems after chronic stress and 6-OHDA-induced neurotoxicity. Unique in its proven abilities to promote healing of the dopaminergic system, rather than just prevent degredation.

6-Hydroxydopamine administration for 28 days (8 microg/2 microL) reduced the number of tyrosine hydroxylase (TH)-immunopositive neurons to 40.2% in the substantia nigra compared to the intact contralateral side. Dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid and norepinephrine levels were reduced to 19.1%, 52.3%, 47.1% and 67.4% in the striatum of 6-hydroxydopamine-lesioned rats compared to the control group, respectively.

However, an oral administration of herbal ethanol extracts from Gynostemma pentaphyllum (GP-EX) (10 mg/kg and 30 mg/kg) starting on day 3 post-lesion for 28 days markedly ameliorated the reduction of TH-immunopositive neurons induced by 6-hydroxydopamine-lesioned rat brain from 40.2% to 67.4% and 75.8% in the substantia nigra.

GP-EX administration (10 and 30 mg/kg) also recovered the levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid and norepinephrine in post-lesion striatum to 64.1% and 65.0%, 77.9% and 89.7%, 82.6% and 90.2%, and 88.1% and 89.2% of the control group.

GP-EX at the given doses did not produce any sign of toxicity such as weight loss, diarrhea and vomiting in rats during the 28 day treatment period and four gypenoside derivatives, gynosaponin TN-1, gynosaponin TN-2, gypenoside XLV and gypenoside LXXIV were identified from GP-EX.

These results suggest that GP-EX might be helpful in the prevention of Parkinson's disease.

http://www.ncbi.nlm....pubmed/20428081



@Normalising
I posted an explanation of D2(short) and D2(long) in my post. Here it is in full. This will give you good foundational knowledge on dopamine receptors and you can use a search engine to find out more.

D1 receptors and D5 are both considered D1-like dopamine receptors, because D5 was cloned shortly after and considered like , in structure and function the D1 receptor....both of these receptors are positively coupled to G-proteins and both activate adenylate cyclase which leads to increased cAMP - which then leads to some degree of stimulation and calcium channel activation.

D2-D3-D4 are all D2-like receptors, they all are negatively coupled to G-proteins with similar biological effects but with distribution that densitites that vary and thus effect researchable outcomes.
D2 receptors have autoreceptors which function to decrease dopamine synthesis / neuron activity...two distinct pathways, but the autoreceptors are ONLY the pre-synaptic ones (D2s), whereas D2 L = D-2-"Long" has it's post-synaptic effects and a stronger downstream effect more indicative of a dopaminergic pathway and having more interaction with the D1-like receptors...


D1 and D5 are largely involved in behavioral responses and energy production/expenditure, they both play a role in cocaine induced hyper-excitation and euphoria, and are necessary in the study of anxiety disorders and depression.

D2,D3,D4 have some similar effects; are involved in memory, sexuality, depressive-phases, response to light and affect heart rate via a central mechanisms - they have involvement in addiction as well and tend to play a role in "channeling" neural activity leading to more transient states if excessively activated....

As I've said, the main reason why dopamine drugs have side-effects is because they activate only D2-like, if they activated both families there would be far less side-effects altogether...

The body/mind is not really set up or made to just accept dopaminergic inputs to one family-type, therefore dopamine drugs are seen as very strange to the human body and it only gets balanced out when you find a separate way to re-activate the cyclic adensoine monophosphate symptoms (as would be done by activating D1-D5 complex's)..therefore, I don't recommend dopamine drugs without the use of either forskolin, or more preferably, a histamine H3 antagonist such as conessine or pitolisant.

@Autumn Knight

Less VMAT (aka down regulated VMAT) will cause undesirable effects in day to day neural functioning.

There exists VMAT 1 and 2. I think VMAT2 is focused in mostly.

Insight into MDMAs properties:

PUTATIVE METHOD OF ACTION
MDMA exerts its effects by reversing the normal operation of vesicular VMAT and neuronal SERT action. In the MDMA-naive and/or "sober" brain, intracellular VMAT consolidates 5-HT from within the cytosol to intracellular vesicles. 5-HT is held in these vesicles until the neuron fires, during which time the vesicle fuses with the neuronal membrane and empties its contents into the synaptic cleft. After binding and subsequently releasing from post pre- and post-synaptic receptors, neuronal SERT recaptures ("reuptakes") the "spent" 5-HT back into the neuron, for the cycle to begin anew. MDMA reverses the function of both the VMAT and SERT proteins, making the neuron efflux a significant percentage of total 5-HT stores directly into the synaptic cleft, thereby flooding the synapse with free 5HT and overstimulating 5-HT1A and 5-HT2A receptors (which are thought to be responsible for MDMA's positive subjective effects).


PUTATIVE MODE OF TOLERANCE
Chronic or severe acute overstimulation of presynaptic 5HT receptors causes a significant downregulation of SERT and VMAT in the presynaptic neuron. Similar overstimulation of postsynaptic 5HT receptors causes a downregulation of 5-HT1A and 5-HT2A expression by the postsynaptic neuron. The "loss of magic" may also be a secondary effect of neurotoxicity resulting from superoxide formation from the breakdown products of MAO metabolism in excess of neuronal antioxidant stores, although this particular mode of tolerance is highly suspect since the retraction of the Ricaurte study suggesting this method of neurotoxicity.


THE LOSS OF MAGIC
Downregulation of SERT and VMAT leads to less active binding sites for MDMA and therefore a slower rise in synaptic 5-HT concentrations. Also, postsynaptic receptor downregulation means a lower maximum response by the postsynaptic signaling chain. These effects combine to convert what was originally, upon administration of MDMA, an exhilirating and overwhelming cascade reaction to a muted, modest increase in 5-HT neurotransmission throughout the system, possibility with higher-order or exponentially-compounding effects as more stages to the system (more linked synapses) are considered.


THE GOAL
Recapturing the ability of MDMA to induce that overwhelming, cascading release of 5-HT throughout the 5-HT system.


THE HYPOTHESIS
Inducing upregulation of SERT, VMAT, 5-HT1A, and 5-HT2A will reverse the mechanism of tolerance, potentially repotentiating the MDMA experience to at or beyond MDMA-naive levels.


AGENTS OF EXPERIMENTATION
Piracteam may increase neuronal membrane permeability, allowing a greater concentration of MDMA to enter the neuronal cytosol and act upon VMAT. Hypericum (Saint John's Wort) upregulates systemic 5-HT1A and 5-HT2A expression with its expectant effects on strength of experience. 5-HTP may increase systemic 5-HT concentrations but may cause chronic downregulation of all mentioned sites of action and therefore will not be considered. Chronic cocaine consumption has been found to cause SERT upregulation but has differing effects on the MDMA experience and therefore will not be considered. Chronic alcohol consumption has been found to upregulate 5-HT1A and 5-HT2A expression. SWIMM knows of no agents found to cause an upregulation of VMAT expression.

Upregulate VMAT:

[b]Lithium ions modulate the expression of VMAT2 in rat brain.

Northern analysis revealed an overall increase (199+/-27%) of the neuronal VMAT isoform (VMAT2) in rat brain after lithium. However, in situ hybridization analysis revealed regional differences in the effects of lithium. Thus, VMAT2 mRNA increased by 50-100% over control in the raphe nuclei, ventral tegmental area, and substantia nigra of rats fed the lithium diet. Concomitantly, VMAT2 mRNA declined by about 50% in the locus coeruleus. Because VMAT2 is expressed in neurons that are strongly implicated in regulating mood and behavior, these data support the hypothesis that alterations of VMAT2 expression contribute to the therapeutic effects of lithium in psychiatric disorders.

www.ncbi.nlm.nih.gov/pubmed/12384252


Sodium Phenylbutyrate upregulates VMAT!!!

From user KoolK3n:

I've been looking for means to upregulate VMAT and found the protein DJ-1:
http://www.ncbi.nlm....pubmed/22887838

http://eprints.lib.h...1-4_813-818.pdf

Sodium Phenylbutyrate upregulates DJ-1 (without neuronal stress) therefore upregulating VMAT2!!
http://en.wikipedia...._phenylbutyrate
http://www.ncbi.nlm....pubmed/21372141

Edited by sativa, 20 August 2016 - 09:21 AM.

[Londonscouser]

Autumn Knight...I'm extremely sorry to hear about the symptoms you have been suffering with for years. I too have from drug-abuse related symptoms for a long time.

 

I was wondering if you could describe how your symptoms have been for the last 8 years ?

 

Also, were you exercising everyday ect ?

 

Good luck with the NSI-189. I was researching about this new substance last year, and i came across a few victims of MDMA abuse who stated that NSI-189 allowed for emotions to be felt once again. In 1 of the cases, this was a permanent effect even 6 months after abstinence of NSI-189

[Autumn Knight]

Autumn Knight...I'm extremely sorry to hear about the symptoms you have been suffering with for years. I too have from drug-abuse related symptoms for a long time.

 

I was wondering if you could describe how your symptoms have been for the last 8 years ?

 

Also, were you exercising everyday ect ?

 

Good luck with the NSI-189. I was researching about this new substance last year, and i came across a few victims of MDMA abuse who stated that NSI-189 allowed for emotions to be felt once again. In 1 of the cases, this was a permanent effect even 6 months after abstinence of NSI-189

 

Thanks.  

 

Extreme anxiety, obsessive thoughts, speech problems (putting words in the wrong order, taking forever to speak the correct sentence, sounding very weird when I talk), issues figuring out problems like math and riddle problems (like before in school I didn't have any trouble with the most difficult material, now I struggle to pull a C in lower level sciences and math), trouble explaining things. Sorry I would put more but I'm running out of time right now. I'm planning on putting all of this into my comprehensive treatment testimonials, which I will post here. 

I do exercise at least 4 days of the week. 

It's not emotions I have the most trouble with, it's cognitive losses. 

 

What are your symptoms?

[Londonscouser]

I got similarish speech problems, trouble explaining things ect and depression stuff...

 

 

[Londonscouser]

I just want to add, and hopefully somebody can elaborate, but i think one day it may be possible to replace your 'damaged' 5-HT neurons...

 

Induced pluripotent stem cells have been around for approximately 10 years now, and the technology consists of reprogramming adult cells via introduction of transcription factors, leading to generation of cells that are in a pluripotent state...and these stem cells can be directed to differentiate into whatever cell is required. The main advantage about this technology is that the cells would be patient-specific...

 

Most work ive read about has been to create dopaminergic neurons for Parkinson's disease sufferers.

[Autumn Knight]

Is that an invasive procedure? 

 

I'm trying to focus on things we can do right now. Keeping things in mind for the future is a good idea, but taking charge right now (which to me means things I can do at home at relatively low cost) is critical. 

[normalizing]

 

www.ncbi.nlm.nih.gov/pubmed/12384252


Sodium Phenylbutyrate upregulates VMAT!!!

From user KoolK3n:

I've been looking for means to upregulate VMAT and found the protein DJ-1:
http://www.ncbi.nlm....pubmed/22887838

http://eprints.lib.h...1-4_813-818.pdf

Sodium Phenylbutyrate upregulates DJ-1 (without neuronal stress) therefore upregulating VMAT2!!
http://en.wikipedia...._phenylbutyrate
http://www.ncbi.nlm....pubmed/21372141

 

 

 

any clues to sources for sodium phenylbutyrate? google keeps telling me just very few european companies sell it, but when i visit their websites, it seems they concentrate on industrial powders for specific use by professionals

Edited by normalizing, 22 August 2016 - 02:27 AM.

[normalizing]

so someone has a clue where to source sodium phenylbutyrate?

[Autumn Knight]

so someone has a clue where to source sodium phenylbutyrate?

 

 

My browser will not currently allow me to post links, so all of this will be handwritten. Sorry.

 

According to thenorthdrugstore.com, Buphenyl, a drug whose active ingredient is phenylbutyrate, is around the $2,000-$3,000 range for a few dozen dosages. If you've got loads of cash to spare, sounds great.

 

Meanwhile, on scandinavianformulas.com, there are 7 different kinds of phen b available. I would opt for the sodium salt kind. I'm going to call them tomorrow to see if they will sell me some. My hopes aren't high that they will. Maybe you could contact some of the other companies that sell it as well. Hopefully the price isn't freakin' ridiculous if either of us manages a green light on phenylbutyrate from any companies that sell it.

Edited by Autumn Knight, 11 September 2016 - 08:16 AM.

[Autumn Knight]

Oh, wait, normalizing.

 

I found something else under triButyrate. Try looking up where to buy it. There is a source on medchemexpress.com.

 

Maybe you can research it a little. I'm planning on looking into it more sometime this week when I have time.

[gamesguru]

happy sunday, all!

Effect of ginseng saponins on enhanced dopaminergic transmission and locomotor hyperactivity induced by nicotine.
Kim SE1, Shim I, Chung JK, Lee MC. (2006)

Several studies have shown that behavioral hyperactivity induced by psychomotor stimulants is prevented by ginseng saponins. In an attempt to investigate whether the effect of ginseng saponins is through their inhibitory action on the enhanced dopaminergic transmission by psychomotor stimulants, we examined the effects of ginseng total saponin (GTS) presynaptically on nicotine-induced dopamine (DA) release in the striatum of freely moving rats using in vivo microdialysis technique and postsynaptically on the in vitro and in vivo binding of [3H]raclopride to DA D2 receptors. Also, we examined the effects of GTS on nicotine-induced locomotor hyperactivity and on nicotine-induced Fos protein expression in the nucleus accumbens and striatum. Systemic pretreatment with GTS (100 and 400 mg/kg, intraperitoneally (i.p.)) resulted in a dose-dependent inhibition of locomotor hyperactivity induced by nicotine. GTS decreased nicotine-induced DA release in the striatum in a dose-dependent manner. However, GTS had no effects on resting levels of locomotor activity and extracellular DA in the striatum. GTS inhibited the in vitro binding of [3H]raclopride to rat striatal membranes with an IC50 of 5.14+/-1.09 microM. High doses of GTS (400 and 800 mg/kg, i.p.) resulted in decreases in the in vivo binding of [3H]raclopride in the striatum. GTS decreased nicotine-induced Fos protein expression in the nucleus accumbens and striatum, reflecting the inhibition by GTS of nicotine-induced enhancement of dopaminergic transmission. The results of the present study suggest that GTS acts not only on dopaminergic neurons directly or indirectly to prevent nicotine-induced DA release but also postsynaptically by binding to DA D2 receptors. This may explain the blocking effect of GTS on behavioral activation induced by nicotine and conceivably by other psychostimulants. Our data raise the possibility that GTS, by attenuating nicotine-induced enhancement of dopaminergic transmission, may prove to be a useful therapeutic agent for nicotine addiction and warrant further investigation on its effect on nicotine's rewarding property.

Ginkgo biloba extract (EGb 761) modulates the expression of dopamine-related genes in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in mice.
Rojas P1, Ruiz-Sánchez E, Rojas C, Ogren SO. (2012)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic neurotoxicity and behavioral impairment in rodents similar to Parkinson's disease. The MPTP mouse model is widely used to evaluate new protective agents. EGb 761 is a well-defined mixture of active compounds extracted from Ginkgo biloba leaves according to a standardized procedure. We have shown that EGb 761 attenuates the loss of striatal dopamine levels and prevents the neurodegeneration of the nigrostriatal pathway induced by MPTP. This finding shows that neuroprotective effects of EGb 761 act, in part, on the dopamine system. Therefore, this study investigates whether EGb 761 exerts dopaminergic neuroprotection through the regulation of dopamine-related gene expression in MPTP-induced Parkinsonism. Male C57BL/6J mice were injected with MPTP (30 mg/kg, i.p.) for 5 days and later with EGb 761 (40 mg/kg, i.p.) daily for 18 days. The expression of selected genes was evaluated in the striatum and midbrain by quantitative PCR. The genes for tyrosine hydroxylase (Th), vesicular monoamine transporter 2 (Vmat2), dopamine transporter (Dat), dopamine D2 receptor (Da-d2r), and transcription factors (Pitx3 and Nurr1) related to dopamine neurotransmission were selected for the analysis. EGb 761 administration to MPTP-treated mice protected Th (41%), Vmat2 (15%), Dat (102%), Da-d2r (46%), Pitx3 (63%), and Nurr1 (148%) mRNA levels in the midbrain, all of which were up-regulated. However, EGb 761 partially reversed the MPTP effect exclusively for Th (48%) and Nurr1 (96%) mRNA in the striatum. Only Th and Nurr1 mRNA and protein levels were regulated by EGb 761 in both regions of the nigrostriatal pathway. This result could be related to the regulation of their transcription. Our results suggest that EGb 761-associated neuroprotection against MPTP neurotoxicity is related to the regulation of the dopamine genes. Moreover, this neuroprotection also involves the regulation of transcription factors such as Nurr1 that are important for the functional maintenance of dopaminergic neurons.

The effects of scopolamine and the nootropic drug phenotropil on rat brain neurotransmitter receptors during testing of the conditioned passive avoidance task
Yu. Yu. Firstova, D. A. Abaimov, I. G. Kapitsa, T. A. Voronina, G. I. Kovalev (2011)

(please note: phenylpiracetam has mixed reports, like uridine)
We studied the effects of administration of the new nootropic drug phenotropil (N-carbamoylmethyl-4-phenyl-2-pyrrolidone) at a dose of 100 mg/kg on the quantitative characteristics of dopamine (DA), serotonin (5-HT), glutamate (NMDA), GABA-A (BDZ), and acetylcholine (nACh) receptors in rats using the conditioned passive avoidance task (PAT) under normal conditions and during scopolamine-induced amnesia ex vivo. We found that the cholinolytic drug scopolamine induced a substantial increase in the density (Bmax) of n-choline receptors in the cortex (by 99% as compared to the control) and NMDA receptors in the hippocampus (by 93%). A single administration of phenotropil (100mg/kg, intraperitoneally) abolished the effect of scopolamine and decreased the number of nACh and NMDA receptors by 46% and 14%, respectively. Phenotropil also abolished the effect of scopolamine on the benzodiazepine receptors and dopamine D1 receptors. Scopolamine decreased the density of D1 receptors by 20% and BDZ receptors by 17%, whereas phenotropil increased the density of receptors by 16% and 25%, respectively. Phenotropil (phenylpiracetam) considerably increased the density of dopamine D2 and D3 receptors by 29% and 62%, respectively. Scopolamine also increased the density of D3 receptors by 44% as compared to the control. We did not find any changes in the binding characteristics of 5-HT2 receptors during scopolamine-induced amnesia or during phenotropil treatment. These results demonstrate the role of these receptors in the development of scopolamine-induced amnesia and in neurochemical mechanisms of the anti-amnestic effects of phenotropil.

Effects of lithium on dopamine D2 receptor expression in the rat brain striatum.
Kameda K1, Miura J, Suzuki K, Kusumi I, Tanaka T, Koyama T. (2001)

Effects of lithium on the dopamine D2 receptor expression in the rat brain striatum were studied. Feeding the chow containing 0.2% LiCO3 for 6 days increased the level of the dopamine D2 receptor mRNA, and the transcription rate of the dopamine D2 receptor gene, indicating the stimulatory effects of lithium on the transcription of the dopamine D2 receptor gene. [3H] Spiperone binding to the striatal membranes increased in the rats treated with lithium, while the Western blotting analysis showed no change of the amount of the dopamine D2 receptors. These results suggested that lithium might induce the conformational changes of the dopamine D2 receptors. The methamphetamine-induced locomotor activity was enhanced by the pretreatment with lithium, whereas simultaneous increase in the methamphetamine concentration in the striatum was also observed. These observations suggested that the stimulation of methamphetamine-induced locomotor activity by lithium might be, at least partly, due to either increased sensitivity of the dopamine receptors, or increased concentration of methamphetamine in brain, or combination of both.

Chronic inositol increases striatal D(2) receptors but does not modify dexamphetamine-induced motor behavior. Relevance to obsessive-compulsive disorder.
Harvey BH1, Scheepers A, Brand L, Stein DJ. (2001)

A large body of evidence suggests that the neuropathology of obsessive-compulsive disorder (OCD) lies in the complex neurotransmitter network of the cortico-striatal-thalamo-cortical (CSTC) circuit, where dopamine (DA), serotonin (5HT), glutamate (Glu), and gamma-amino butyric acid (GABA) dysfunction have been implicated in the disorder. Chronic inositol has been found to be effective in specific disorders that respond to selective serotonin reuptake inhibitors (SSRIs), including OCD, panic, and depression. This selective mechanism of action is obscure. Since nigro-striatal DA tracts are subject to 5HT(2) heteroreceptor regulation, one possible mechanism of inositol in OCD may involve its effects on inositol-dependent receptors, especially the 5HT(2) receptor, and a resulting effect on DA pathways in the striatum. In order to investigate this possible interaction, we exposed guinea pigs to oral inositol (1.2 g/kg) for 12 weeks. Subsequently, effects on locomotor behavior (LB) and stereotype behavior (SB), together with possible changes to striatal 5HT(2) and D(2) receptor function, were determined. In addition, the effects of chronic inositol on dexamphetamine (DEX)-induced motor behavior were evaluated. Acute DEX (3 mg/kg, ip) induced a significant increase in both SB and LB, while chronic inositol alone did not modify LA or SB. The behavioral response to DEX was also not modified by chronic inositol pretreatment. However, chronic inositol induced a significant increase in striatal D(2) receptor density (B(max)) with a slight, albeit insignificant, increase in 5HT(2) receptor density. This suggests that D(2) receptor upregulation may play an important role in the behavioral effects of inositol although the role of the 5HT(2) receptor in this response is questionable.

Neuroprotective potential of Bacopa monnieri and Bacoside A against dopamine receptor dysfunction in the cerebral cortex of neonatal hypoglycaemic rats.
Thomas RB1, Joy S, Ajayan MS, Paulose CS. (2013)

Neonatal hypoglycaemia initiates a series of events leading to neuronal death, even if glucose and glycogen stores return to normal. Disturbances in the cortical dopaminergic function affect memory and cognition. We recommend Bacopa monnieri extract or Bacoside A to treat neonatal hypoglycaemia. We investigated the alterations in dopaminergic functions by studying the Dopamine D1 and D2 receptor subtypes. Receptor-binding studies revealed a significant decrease (p < 0.001) in dopamine D1 receptor number in the hypoglycaemic condition, suggesting cognitive dysfunction. cAMP content was significantly (p < 0.001) downregulated in hypoglycaemic neonatal rats indicating the reduction in cell signalling of the dopamine D1 receptors. It is attributed to the deficits in spatial learning and memory. Hypoglycaemic neonatal rats treated with Bacopa extract alone and Bacoside A ameliorated the dopaminergic and cAMP imbalance as effectively as the glucose therapy. The upregulated Bax expression in the present study indicates the high cell death in hypoglycaemic neonatal rats. Enzyme assay of SOD confirmed cortical cell death due to free radical accumulation. The gene expression of SOD in the cortex was significantly downregulated (p < 0.001). Bacopa treatment showed a significant reversal in the altered gene expression parameters (p < 0.001) of Bax and SOD. Our results suggest that in the rat experimental model of neonatal hypoglycaemia, Bacopa extract improved alterations in D1, D2 receptor expression, cAMP signalling and cell death resulting from oxidative stress. This is an important area of study given the significant motor and cognitive impairment that may arise from neonatal hypoglycaemia if proper treatment is not implemented.

[tronatula2]

 

happy sunday, all!

Neuroprotective potential of Bacopa monnieri and Bacoside A against dopamine receptor dysfunction in the cerebral cortex of neonatal hypoglycaemic rats.
Thomas RB1, Joy S, Ajayan MS, Paulose CS. (2013)

Neonatal hypoglycaemia initiates a series of events leading to neuronal death, even if glucose and glycogen stores return to normal. Disturbances in the cortical dopaminergic function affect memory and cognition. We recommend Bacopa monnieri extract or Bacoside A to treat neonatal hypoglycaemia. We investigated the alterations in dopaminergic functions by studying the Dopamine D1 and D2 receptor subtypes. Receptor-binding studies revealed a significant decrease (p < 0.001) in dopamine D1 receptor number in the hypoglycaemic condition, suggesting cognitive dysfunction. cAMP content was significantly (p < 0.001) downregulated in hypoglycaemic neonatal rats indicating the reduction in cell signalling of the dopamine D1 receptors. It is attributed to the deficits in spatial learning and memory. Hypoglycaemic neonatal rats treated with Bacopa extract alone and Bacoside A ameliorated the dopaminergic and cAMP imbalance as effectively as the glucose therapy. The upregulated Bax expression in the present study indicates the high cell death in hypoglycaemic neonatal rats. Enzyme assay of SOD confirmed cortical cell death due to free radical accumulation. The gene expression of SOD in the cortex was significantly downregulated (p < 0.001). Bacopa treatment showed a significant reversal in the altered gene expression parameters (p < 0.001) of Bax and SOD. Our results suggest that in the rat experimental model of neonatal hypoglycaemia, Bacopa extract improved alterations in D1, D2 receptor expression, cAMP signalling and cell death resulting from oxidative stress. This is an important area of study given the significant motor and cognitive impairment that may arise from neonatal hypoglycaemia if proper treatment is not implemented.

 

 

So why are there many anecdotal reports that Bacopa Decreases motivation?

[sativa]

Perhaps because those users had brain chemistry that resulted in a motivation decrease due to Bacopa use? (Including perhaps Bacopa's other modes of action)

[gamesguru]

So why are there many anecdotal reports that Bacopa Decreases motivation?

 

Possibly due to the global serotonin increase^[1], and subsequent 5-HT2C activation.  Inhibition of the 2C receptor is implicated in accumbal dopamine release.  Activation of it does the opposite, inhibiting the dopamine release^[2].  It also has a very mild effect on lowering glutamate and norepinephrine, something like 5-8%.  Last ideas are acetylcholine as anti-dopamine^[3] (you know bacopa is cholinergic?) or related to thryoid hormones (unlikely).

[DomoTheHungry]

has anybody gotten to try the sodium butyrate? I am also interested in this thread. I have anhedonia, speech problems(cant talk loud enough, when I do its weird and angry ish,), as well as some cognitive problems.  Literally from a night of adderall and mdma with cocaine 8 months ago.  My dopamine system hasn't much improved since then

 

If it would help anyone I tried the following:

lithium upreg d2 worked the best the first time after i felt like i capped out on its benefits,

inositol upreg d2 helps motivation but not emotions

 uridine helped the most the first time turned my world from black to grey.. but like lithium i felt it capped out

im using 9-methyl-beta-carboline right now to regrow dopamine axon neurons.  Its been two weeks but my coordination is slightly better and its a mild mood booster + motivation but no help in anhedonia

 

Edited by DomoTheHungry, 08 November 2016 - 05:34 AM.

[sativa]

To support optimal dopamine system function, ensure required nutrients are available in adequate amounts. From the top of my head:

Vitamin B3
Manganese
Magnesium

Vitamin B12 will likely okay an important role also.

Also, NAC might be beneficial for restoring/supporting dopamine system function

[gamesguru]

So is forskolin, ginseng, uridine and a ton of other stuff.

[normalizing]

i have drd2 reduced expression and denisity and i tried all the crap gamesguru and sativa recommend and none of them worked but they seem persistent and even though they dont have the same problem and cannot know for sure it works at all on actual person with that problem, they should kindly stfu ok thank you.

 

autumn knight thanks for taking this issue seriously unlike those two clowns posting their stupid herb links. i appreciate it A LOT and ill check medchemexpress.com. and yes, this stuff is hard to find damn it and it seems that those high prices are for a reason. it has good medicinal value so far from the research i have seen. hopefully one of is able to one day find it cheap *sigh*

[Autumn Knight]

TriButyrate is not very expensive at all but I haven't gotten the chance to try it yet. It's on the list.

 

As for the others posting what they know about what can help, they are offering all they have. They don't have to try to help at all, and there is research to back up what they are offering, so they are giving all they can. Unfortunately, people who have experienced this problem rarely congregate in the same place, so we've got to try with what we have. As for why the substances didn't work for you, these guys could not know that based on the research they have found supporting these herbs as possibly helpful.

[normalizing]

autumn knight i apologized, i didn mean to be rude to them to such noticable degree but those two guys have been on my case all over the forum for a while recommending the same herbs ive done when i was a teenager and didnt work for me and yet they keep harassing me with their studies and saying i didnt do it right or something.... really annoying.

i mean those kids are obvously new to all this and any study done on a rat probably gets them all aroused as it was arousing to me , all obsessed when i was 10, but now that im 22 years older thats kind of laughable im sorry, please seize bothering me kids. go report your herb studies elsewhere, try the kindergarden. ive tried your herbs, ive done them extensively, im older than you kids, please stop harassing me, ok thanks

Edited by normalizing, 09 November 2016 - 10:10 AM.

[DomoTheHungry]

hey guys what about repairing DAT and SERT? Are there substances for those? I have ocd and I been reading around the low availability in those transporters are implicated in ocd and depression.

[jack black]

i did gene test and it shows i have reduced expression and low density on DRD2 receptor which from what i know is related to drug addiction and such.

Could you please explain how did you figure it out from the 23 and me? I did that too and paid for the interp and don't remember anything on this.

[PeaceAndProsperity]

hey guys what about repairing DAT and SERT? Are there substances for those? I have ocd and I been reading around the low availability in those transporters are implicated in ocd and depression.

It's complete and utter nonsense. Low serotonin does not cause ocd, maybe with extremely rare exceptions. High serotonin and glutamate is implicated in and definitely causes ocd. I've never heard of dopamine antagonists causing ocd but likewise with agonists. 

Most people who've experimented with serotonin precursors and agonists will realize that higher serotonin is actually sometimes the cause of depressive moods.

 

 

As for Normalizing, I don't personally know you but based upon your writing style you seem to be the opposite of someone with low dopamine/D2 receptor expression. 

23andme is pretty useless.

Edited by RatherBeUnknown, 10 November 2016 - 02:50 PM.

[jack black]

My bad, I went back to my 23andme data (I find the free codegen interp most helpful), and DRD2 SNPs were there. I guess rs1800497 is most important. I have no abnormalities here, so I forgot about it.

But here is the thing, based on that SNP I should have no ADHD, no OCD, no obesity, better avoidance of errors, more postop nausea, and less alcohol dependency. They are all wrong, except for alcohol.

[DomoTheHungry]

 

hey guys what about repairing DAT and SERT? Are there substances for those? I have ocd and I been reading around the low availability in those transporters are implicated in ocd and depression.

It's complete and utter nonsense. Low serotonin does not cause ocd, maybe with extremely rare exceptions. High serotonin and glutamate is implicated in and definitely causes ocd. I've never heard of dopamine antagonists causing ocd but likewise with agonists. 

Most people who've experimented with serotonin precursors and agonists will realize that higher serotonin is actually sometimes the cause of depressive moods.

 

 

As for Normalizing, I don't personally know you but based upon your writing style you seem to be the opposite of someone with low dopamine/D2 receptor expression. 

23andme is pretty useless.

 

 

How come lots of people including myself feel better from inositol which raises intracellular serotonin? 

[jack black]

hey guys what about repairing DAT and SERT? Are there substances for those? I have ocd and I been reading around the low availability in those transporters are implicated in ocd and depression.

It's complete and utter nonsense. Low serotonin does not cause ocd, maybe with extremely rare exceptions. High serotonin and glutamate is implicated in and definitely causes ocd. I've never heard of dopamine antagonists causing ocd but likewise with agonists.
Most people who've experimented with serotonin precursors and agonists will realize that higher serotonin is actually sometimes the cause of depressive moods.


As for Normalizing, I don't personally know you but based upon your writing style you seem to be the opposite of someone with low dopamine/D2 receptor expression.
23andme is pretty useless.

How come lots of people including myself feel better from inositol which raises intracellular serotonin?

Because inositol antagonizes 5ht2a receptors.

[PeaceAndProsperity]

How come lots of people including myself feel better from inositol which raises intracellular serotonin? 

 

How come everytime there's a thread on lowering serotonin then inositol is recommended when so many studies indicate that it increases serotonin and its side-effects clearly point to it as well?

[jack black]

How come lots of people including myself feel better from inositol which raises intracellular serotonin?

How come everytime there's a thread on lowering serotonin then inositol is recommended when so many studies indicate that it increases serotonin and its side-effects clearly point to it as well?

How come no one links those said studies?