89 replies to this topic

[the_apollo]

Since i found an article detailing how D2-receptor expression in the Nucleus Accumbens 'enhance motivation', I once again started looking for things that will increase the Dopamine D2-receptor expression in the NAcc,
(with extension also the rest of the striatum, but mainly the NAcc).
So far i have not found more than two drugs that actually increase D2-receptor expression in the NAcc, so i included those i know increases the receptor expression in the striatum and that is likely to act on the NAcc,

though not stated in papers as the NAcc is a part of the striatum.
 

Fluoxetine and desipramine both increases postsynaptic D2-receptor expression in NAcc". (first one is an SSRI, second is an TCA)

http://www.ncbi.nlm..../pubmed/9888623
 

Inositol increases striatal D(2) receptors. (i have not figured if only postsynaptic, therefore assumes its both)

http://www.ncbi.nlm....pubmed/11267629
 

(forskolin) Dopamine D2 receptor upregulation in rat neostriatum following in vivo infusion of forskolin.

http://www.ncbi.nlm..../pubmed/9376541

 

 

Though forskolin seems not to be a good way as the same study states;

(D2S/autoreceptor) This increase was 2.5-fold higher than that found for the hD2L receptor

 

.. Meaning that Forskolin increases the levels of the dopamine autoreceptor much more than the "good" postsynaptic receptor,

not only bad because it tells the DAT enzyme to "vacuum" up the dopamine back in presynapse, but also because the D2-autoreceptor is involved in negative signaling to the tyrosine-hydroxylase enzymes.

Anyway, those few is what i could find does actually increase D2-receptor expression, not just "possibly" or in trials where they delivered the drug via intracranial methods.

 

Despite it's importance, there does not seem to be very much research done on what increases dopamine receptor-levels, and even less regarding NAcc...

So i am asking this: Is there anything else that can induce an upregulation of striatal or nucleus accumbens -D2 receptor level/expression?

 

 

 

"D2-autoreceptor involvance in TH-enzymes":

http://www.ncbi.nlm....pubmed/11207812

 

"D2-receptor expression in NAcc linked to motivation"

http://www.ncbi.nlm....pubmed/23711983

[AOLministrator]

try GHB 1.5g

Edited by Aolministrator, 24 January 2015 - 10:41 PM.

[jaiho]

That's why i believe Fluoxetine is the best SSRI. It increases motivation nicely for me.

While Sertraline has more affinity on dopamine, im pretty sure it's mechanism is different.

 

The combination of fluoxetine & desipramine smashed depression:

http://www.ncbi.nlm..../pubmed/2009031

 

Edited by jaiho, 26 January 2015 - 12:44 AM.

[Area-1255]

Phenyl piracetam and tianeptine should work wonders to increase dopamine receptor expression.

Also, you need dopamine D2S autoreceptors as those happen to be the ones that inhibit prolactin, unfortunately.

 

The Physiology, Signaling, and Pharmacology of Dopamine Receptors

 

http://link.springer...819712411020048

 

 

 

The effects of scopolamine and the nootropic drug phenotropil on rat brain neurotransmitter receptors during testing of the conditioned passive avoidance task Abstract

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 (B max) 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 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.

Original Russian Text © Yu.Yu. Firstova, D.A. Abaimov, I.G. Kapitsa, T.A. Voronina, G.I. Kovalev, 2011, published in Neirokhimiya, 2011, Vol. 28, No. 2, pp. 130–141.

 

Behav Pharmacol. 2002 Mar;13(2):127-38.   

http://www.ncbi.nlm....pubmed/11981225 Effect of repeated treatment with tianeptine and fluoxetine on central dopamine D(2) /D(3) receptors.

Dziedzicka-Wasylewska M1, Rogoz Z, Skuza G, Dlaboga D, Maj J.

Author information

 

Abstract

Tianeptine (TIA) is an antidepressant drug that has been shown to decrease extracellular serotonin level and reveals no affinity for neurotransmitter receptors. The present study was aimed at determining whether repeated TIA treatment induced any adaptive changes in the central dopamine D(2)/D(3) system (behavioural and biochemical) similar to those reported earlier for tricyclic antidepressants. Experiments were carried out on male Wistar rats. TIA was administered at a dose of 5 and 10 mg/kg once or repeatedly (twice daily for 14 days). Fluoxetine (FLU), used as a reference compound, was also administered at a dose of 10 mg/kg. The results obtained showed that TIA or FLU administered repeatedly increased the hyperlocomotion induced by D-amphetamine and 7-hydroxy-dipropylaminotetralin (7-OH-DPAT). Biochemical study revealed a decrease in the [(3)H]7-OH-DPAT binding sites after acute and repeated treatment with TIA or FLU in the islands of Calleja minor, as well as in the shell part of nucleus accumbens septi. On the other hand, both TIA and FLU administered repeatedly increased the binding of [(3)H]quinpirole (a D(2)/D(3) receptor agonist) in the nucleus caudatus as well as in the core part of the nucleus accumbens septi. Similar effects have been observed when dopamine D(2)/D(3) receptors were visualized with the use of [3H]raclopride, a dopamine D(2)/D(3) receptor antagonist. However, TIA and FLU induced a decrease in the level of mRNA encoding for dopamine D(2) receptors, not only after repeated but also after acute treatment. These results indicate that repeated TIA and FLU administration induces adaptive changes in the dopaminergic D(2)/D(3) system and especially enhances the functional responsiveness of dopamine D(2) and D(3) receptors. However, the question of whether this increased responsiveness is important for clinical antidepressant efficacy remains open.

PMID:   11981225   [PubMed - indexed for MEDLINE]

 

Edited by Area-1255, 29 January 2015 - 10:49 PM.

[CognitiveNeuro]

Weirdly, phenylpiracetam has the effects of downregulation of D2 (amphetamine tolerance). 

 

 

 

 

 

Phenyl piracetam and tianeptine should work wonders to increase dopamine receptor expression.

Also, you need dopamine D2S autoreceptors as those happen to be the ones that inhibit prolactin, unfortunately.

 

The Physiology, Signaling, and Pharmacology of Dopamine Receptors

 

http://link.springer...819712411020048

 

 

 

The effects of scopolamine and the nootropic drug phenotropil on rat brain neurotransmitter receptors during testing of the conditioned passive avoidance task Abstract

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 (B max) 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 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.

Original Russian Text © Yu.Yu. Firstova, D.A. Abaimov, I.G. Kapitsa, T.A. Voronina, G.I. Kovalev, 2011, published in Neirokhimiya, 2011, Vol. 28, No. 2, pp. 130–141.

 

Behav Pharmacol. 2002 Mar;13(2):127-38.   

http://www.ncbi.nlm....pubmed/11981225 Effect of repeated treatment with tianeptine and fluoxetine on central dopamine D(2) /D(3) receptors.

Dziedzicka-Wasylewska M1, Rogoz Z, Skuza G, Dlaboga D, Maj J.

Author information

 

Abstract

Tianeptine (TIA) is an antidepressant drug that has been shown to decrease extracellular serotonin level and reveals no affinity for neurotransmitter receptors. The present study was aimed at determining whether repeated TIA treatment induced any adaptive changes in the central dopamine D(2)/D(3) system (behavioural and biochemical) similar to those reported earlier for tricyclic antidepressants. Experiments were carried out on male Wistar rats. TIA was administered at a dose of 5 and 10 mg/kg once or repeatedly (twice daily for 14 days). Fluoxetine (FLU), used as a reference compound, was also administered at a dose of 10 mg/kg. The results obtained showed that TIA or FLU administered repeatedly increased the hyperlocomotion induced by D-amphetamine and 7-hydroxy-dipropylaminotetralin (7-OH-DPAT). Biochemical study revealed a decrease in the [(3)H]7-OH-DPAT binding sites after acute and repeated treatment with TIA or FLU in the islands of Calleja minor, as well as in the shell part of nucleus accumbens septi. On the other hand, both TIA and FLU administered repeatedly increased the binding of [(3)H]quinpirole (a D(2)/D(3) receptor agonist) in the nucleus caudatus as well as in the core part of the nucleus accumbens septi. Similar effects have been observed when dopamine D(2)/D(3) receptors were visualized with the use of [3H]raclopride, a dopamine D(2)/D(3) receptor antagonist. However, TIA and FLU induced a decrease in the level of mRNA encoding for dopamine D(2) receptors, not only after repeated but also after acute treatment. These results indicate that repeated TIA and FLU administration induces adaptive changes in the dopaminergic D(2)/D(3) system and especially enhances the functional responsiveness of dopamine D(2) and D(3) receptors. However, the question of whether this increased responsiveness is important for clinical antidepressant efficacy remains open.

PMID:   11981225   [PubMed - indexed for MEDLINE]

 

 

Weirdly, phenylpiracetam has the effects of downregulation of D2 (amphetamine tolerance). 

 

 

 

 

 

Phenyl piracetam and tianeptine should work wonders to increase dopamine receptor expression.

Also, you need dopamine D2S autoreceptors as those happen to be the ones that inhibit prolactin, unfortunately.

 

The Physiology, Signaling, and Pharmacology of Dopamine Receptors

 

http://link.springer...819712411020048

 

 

 

The effects of scopolamine and the nootropic drug phenotropil on rat brain neurotransmitter receptors during testing of the conditioned passive avoidance task Abstract

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 (B max) 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 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.

Original Russian Text © Yu.Yu. Firstova, D.A. Abaimov, I.G. Kapitsa, T.A. Voronina, G.I. Kovalev, 2011, published in Neirokhimiya, 2011, Vol. 28, No. 2, pp. 130–141.

 

Behav Pharmacol. 2002 Mar;13(2):127-38.   

http://www.ncbi.nlm....pubmed/11981225 Effect of repeated treatment with tianeptine and fluoxetine on central dopamine D(2) /D(3) receptors.

Dziedzicka-Wasylewska M1, Rogoz Z, Skuza G, Dlaboga D, Maj J.

Author information

 

Abstract

Tianeptine (TIA) is an antidepressant drug that has been shown to decrease extracellular serotonin level and reveals no affinity for neurotransmitter receptors. The present study was aimed at determining whether repeated TIA treatment induced any adaptive changes in the central dopamine D(2)/D(3) system (behavioural and biochemical) similar to those reported earlier for tricyclic antidepressants. Experiments were carried out on male Wistar rats. TIA was administered at a dose of 5 and 10 mg/kg once or repeatedly (twice daily for 14 days). Fluoxetine (FLU), used as a reference compound, was also administered at a dose of 10 mg/kg. The results obtained showed that TIA or FLU administered repeatedly increased the hyperlocomotion induced by D-amphetamine and 7-hydroxy-dipropylaminotetralin (7-OH-DPAT). Biochemical study revealed a decrease in the [(3)H]7-OH-DPAT binding sites after acute and repeated treatment with TIA or FLU in the islands of Calleja minor, as well as in the shell part of nucleus accumbens septi. On the other hand, both TIA and FLU administered repeatedly increased the binding of [(3)H]quinpirole (a D(2)/D(3) receptor agonist) in the nucleus caudatus as well as in the core part of the nucleus accumbens septi. Similar effects have been observed when dopamine D(2)/D(3) receptors were visualized with the use of [3H]raclopride, a dopamine D(2)/D(3) receptor antagonist. However, TIA and FLU induced a decrease in the level of mRNA encoding for dopamine D(2) receptors, not only after repeated but also after acute treatment. These results indicate that repeated TIA and FLU administration induces adaptive changes in the dopaminergic D(2)/D(3) system and especially enhances the functional responsiveness of dopamine D(2) and D(3) receptors. However, the question of whether this increased responsiveness is important for clinical antidepressant efficacy remains open.

PMID:   11981225   [PubMed - indexed for MEDLINE]

 

 

[Area-1255]

 

Weirdly, phenylpiracetam has the effects of downregulation of D2 (amphetamine tolerance). 

 

Study?

[Gorthaur]

 

Weirdly, phenylpiracetam has the effects of downregulation of D2 (amphetamine tolerance). 

 

 

There was a study which showed that phenylpiracetam is actually a dopamine reuptake inhibitor, which would explain the downregulation of D2. Subjectively, I thought it felt like a dopamine/norepinephrine releaser.

[HappyShoe]

Phenylpiracetam did nothing for me, granted I only took it for 3 days, but I took massive doses. Figured I'd share my experience, even if it is limited. I know that's a ridiculously short amount of time, so probably not helpful. Granted, I also have a near immunity to amphetamines at this point, except for wakefulness and possibly hypertension.

Edited by HappyShoe, 30 January 2015 - 03:56 AM.

[Area-1255]

 

 

Weirdly, phenylpiracetam has the effects of downregulation of D2 (amphetamine tolerance). 

 

 

There was a study which showed that phenylpiracetam is actually a dopamine reuptake inhibitor, which would explain the downregulation of D2. Subjectively, I thought it felt like a dopamine/norepinephrine releaser.

 

Why would a DRI downregulate D2R's?

Edited by Area-1255, 30 January 2015 - 03:37 AM.

[meth_use_lah]

http://link.springer...819712411020048

 

 

 

Phenotropil considerably increased the density of dopamine D2 and D3 receptors by 29% and 62%, respectively.

 

[mindpatch]

 

Phenyl piracetam and tianeptine should work wonders to increase dopamine receptor expression.

Also, you need dopamine D2S autoreceptors as those happen to be the ones that inhibit prolactin, unfortunately.

 

The Physiology, Signaling, and Pharmacology of Dopamine Receptors

 

http://link.springer...819712411020048

 

 

 

The effects of scopolamine and the nootropic drug phenotropil on rat brain neurotransmitter receptors during testing of the conditioned passive avoidance task Abstract

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 (B max) 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 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.

Original Russian Text © Yu.Yu. Firstova, D.A. Abaimov, I.G. Kapitsa, T.A. Voronina, G.I. Kovalev, 2011, published in Neirokhimiya, 2011, Vol. 28, No. 2, pp. 130–141.

 

Behav Pharmacol. 2002 Mar;13(2):127-38.   

http://www.ncbi.nlm....pubmed/11981225 Effect of repeated treatment with tianeptine and fluoxetine on central dopamine D(2) /D(3) receptors.

Dziedzicka-Wasylewska M1, Rogoz Z, Skuza G, Dlaboga D, Maj J.

Author information

 

Abstract

Tianeptine (TIA) is an antidepressant drug that has been shown to decrease extracellular serotonin level and reveals no affinity for neurotransmitter receptors. The present study was aimed at determining whether repeated TIA treatment induced any adaptive changes in the central dopamine D(2)/D(3) system (behavioural and biochemical) similar to those reported earlier for tricyclic antidepressants. Experiments were carried out on male Wistar rats. TIA was administered at a dose of 5 and 10 mg/kg once or repeatedly (twice daily for 14 days). Fluoxetine (FLU), used as a reference compound, was also administered at a dose of 10 mg/kg. The results obtained showed that TIA or FLU administered repeatedly increased the hyperlocomotion induced by D-amphetamine and 7-hydroxy-dipropylaminotetralin (7-OH-DPAT). Biochemical study revealed a decrease in the [(3)H]7-OH-DPAT binding sites after acute and repeated treatment with TIA or FLU in the islands of Calleja minor, as well as in the shell part of nucleus accumbens septi. On the other hand, both TIA and FLU administered repeatedly increased the binding of [(3)H]quinpirole (a D(2)/D(3) receptor agonist) in the nucleus caudatus as well as in the core part of the nucleus accumbens septi. Similar effects have been observed when dopamine D(2)/D(3) receptors were visualized with the use of [3H]raclopride, a dopamine D(2)/D(3) receptor antagonist. However, TIA and FLU induced a decrease in the level of mRNA encoding for dopamine D(2) receptors, not only after repeated but also after acute treatment. These results indicate that repeated TIA and FLU administration induces adaptive changes in the dopaminergic D(2)/D(3) system and especially enhances the functional responsiveness of dopamine D(2) and D(3) receptors. However, the question of whether this increased responsiveness is important for clinical antidepressant efficacy remains open.

PMID:   11981225   [PubMed - indexed for MEDLINE]

 

Ok, this is interesting.  The severe anxiety I've been experiencing for the last two years I've slowly realized is possibly due to glutamate and acetylcholine overexpression.  I've tried some racetam based nootropics such as Noopepet and have taken choline supplements and they've caused severe anxiety.  I've recently had great results from taking Memantine, which is an NMDA antagonist.  I think that has essentially turned down the nACh/NMDA volume for me.  It's allowed me to go back on NSI-189, which I think is working really well synergistically with 9 methyl b carboline.  Phenylpiracetam looks like an interesting possibility to decrease the anxiety producing volume of NMDA/nACh and increase expression of DA, but I would want to create permanent changes not develop a tolerance that would downregulate DA long term. 

 

The last week my anxiety has been under control and I've been feeling pretty damn good.  Now I need to get my cognitive abilities back to where they were and increase my libido.  I've been in a dark place for a while, but finally feel like I might be turning a corner.  So far my combination is working. Oh, I'm also taking Uridine and Theanine

[Gorthaur]

 

 

 

Weirdly, phenylpiracetam has the effects of downregulation of D2 (amphetamine tolerance). 

 

 

There was a study which showed that phenylpiracetam is actually a dopamine reuptake inhibitor, which would explain the downregulation of D2. Subjectively, I thought it felt like a dopamine/norepinephrine releaser.

 

Why would a DRI downregulate D2R's?

 

 

More dopamine in the synapse causes the cell to produce fewer dopamine receptors in order to maintain homeostasis. Or, it could be the case that overstimulation of receptors triggers endocytosis of the receptors, and then they aren't replaced.

[Area-1255]

 

 

 

 

Weirdly, phenylpiracetam has the effects of downregulation of D2 (amphetamine tolerance). 

 

 

There was a study which showed that phenylpiracetam is actually a dopamine reuptake inhibitor, which would explain the downregulation of D2. Subjectively, I thought it felt like a dopamine/norepinephrine releaser.

 

Why would a DRI downregulate D2R's?

 

 

More dopamine in the synapse causes the cell to produce fewer dopamine receptors in order to maintain homeostasis. Or, it could be the case that overstimulation of receptors triggers endocytosis of the receptors, and then they aren't replaced.

 

Unless your brain is constantly making new cells and receptors

That's the point of stacking substances that increase expression, with neurotrophic substances such as NSI-189 and / or 9-me-bc.

[Arjuna]

Regarding the forskolin up-regulating the auto-receptor, do we know if that receptor type ratio is unusual?  Maybe it is normal for there to be 2.5 times more autoreceptors than the "good" ones, and the forskolin is simply turning up the normal production for all of them.

 

If anyone is knowledgeable on this subject please chime in, as I struggle with motivation and take forskolin.

 

My subjective experience with forskolin is that it does make me more sensitive to the highs of life.  Smoking a cigarette can give me a really powerful rush and my libido seems stronger.  On other forums people claim it helps against amphetamine tolerance.

 

Keep up the good work, OP.

[normalizing]

Phenylpiracetam did nothing for me, granted I only took it for 3 days, but I took massive doses. Figured I'd share my experience, even if it is limited. I know that's a ridiculously short amount of time, so probably not helpful. Granted, I also have a near immunity to amphetamines at this point, except for wakefulness and possibly hypertension.

 

did you take it as powder from those shady nootropic websites?

[Area-1255]

 

Phenylpiracetam did nothing for me, granted I only took it for 3 days, but I took massive doses. Figured I'd share my experience, even if it is limited. I know that's a ridiculously short amount of time, so probably not helpful. Granted, I also have a near immunity to amphetamines at this point, except for wakefulness and possibly hypertension.

 

did you take it as powder from those shady nootropic websites?

 

Actually, I've found transhuman tech, ceretropic, teamtlr, to all be legitimate and I was pleased with all of them I don't know about any others ; but those three I like.

[CognitiveNeuro]

Regarding the forskolin up-regulating the auto-receptor, do we know if that receptor type ratio is unusual?  Maybe it is normal for there to be 2.5 times more autoreceptors than the "good" ones, and the forskolin is simply turning up the normal production for all of them.

 

If anyone is knowledgeable on this subject please chime in, as I struggle with motivation and take forskolin.

 

My subjective experience with forskolin is that it does make me more sensitive to the highs of life.  Smoking a cigarette can give me a really powerful rush and my libido seems stronger.  On other forums people claim it helps against amphetamine tolerance.

 

Keep up the good work, OP.

 

Can you tell me which forums? I could not find any anecdotal reports of this.

[meth_use_lah]

Regarding the forskolin up-regulating the auto-receptor, do we know if that receptor type ratio is unusual?  Maybe it is normal for there to be 2.5 times more autoreceptors than the "good" ones, and the forskolin is simply turning up the normal production for all of them.

 

If anyone is knowledgeable on this subject please chime in, as I struggle with motivation and take forskolin.

 

My subjective experience with forskolin is that it does make me more sensitive to the highs of life.  Smoking a cigarette can give me a really powerful rush and my libido seems stronger.  On other forums people claim it helps against amphetamine tolerance.

 

Keep up the good work, OP.

 

I took forskolin for a month a while back trying to regulate an immune response but noticed that I actually felt more motivated to get things done, I already knew about it potentially up-regulating d2 receptors but assumed it was unnoticeable since I hadn't seen anyone raving about it.

[Arjuna]

Forskolin increasing motivation could be caused by other things like higher thyroid output, who knows.  

 

Here is the reddit post I referred to earlier with the amphetamine tolerance comment:

 http://www.reddit.co...ne_sensitivity/

 

So basically, if there are ciltep posts about reduced tolerance to amphetamines or increased motivation, then that may support using forskolin for dopamine, too, as ciltep simply raises cAMP.  In fact, the entire mecahinism behind ciltep's cognitive effects could just be dopaminergic in nature, as raised cAMP may increase both dopamine receptors and dopamine production.

http://www.longecity...-my-ciltep-log/

 

There are a couple of posts on bodybuilding forums about forskolin having mood boosting and anxiety reducing properties such as these: 

http://www.mindandmu...iolytic-effects

http://www.mindandmu...vity-motivation

 

I hardly understand the ramifications of raising cAMP as it activates a whole myriad of processes, too many to start listing here.  The ciltep supporters claim it's safe.  There have been 12 week studies using 50mg forskolin in men with no health concerns, and it is a popular supplement, but there isn't any long term data on its safety profile.

 

***The question that still stands to be answered is whether it is normal for the D2 receptors to have 2.5 times more pre-synaptic autoreceptors than post-synaptic receptors.***

If it is normal, it would support using forskolin for motivation and D2 receptors. I tried looking up info on this and got absolutely nowhere.

 

__________________________________

Besides all this forksolin talk, I'd like to share the supplements that have helped me the most with motivation.  Rhodiola is unreal, it squashes anxiety so that I can do what I've set out to do, and may be inhibiting COMT or something.  Magnesium glycinate is a godsend, as it also stops the anxiety tailspin, I think I have overactive NMDA, which does downregulate dopamine receptors. Research magnesium's effects on depression and drug withdrawals (for example http://www.medical-h...abstract?cc=y).  Zinc for keeping prolactin down. And, of course, the holy grail of supplements, Omega 3.  Also, a few weeks of abstaining from sex and porn always works for accomplishing any goal.

Edited by Arjuna, 03 February 2015 - 05:15 PM.

[normalizing]

i was doing forskolin for a long time and didnt notice anything. keep in mind, i tried 3 different forskolin supplements so chance i was doing the shitty one are low.

[barbelith42]

It's important to note that you can experience the subjective sensations of diminished anticipatory reward (a.k.a. motivation) and consummatory reward as a result of more than one dopaminergic dysfunction in the NAcc/Striatum -- not just a lack of D2Rs. There is a complex feedback/feedforward regulatory mechanism that acts to keep your brain working at peak survival efficacy by keeping you from having too much or too little dopamine, as well as from allowing your nervous system from firing too quickly and/or too hot and damaging your neural wiring. You can have D2R downregulation as a result of excess extracellular dopamine and subsequent downregulation (mediated at least in part by the D2 autoreceptor mentioned above); but, you can also have symptoms of cortical-striatal-thalamic dopamine dysfunction as a result of deficient vesicular dopamine release in the presence of too many D2Rs. The real issue here is that you can affect different dopamine receptors in different areas in different quantities, which can lead to some serious negative effects. E.g., cocaine can induce striatal D2R downregulation, but NAcc D3R upregulation. Also recall VTA innervation of these areas and the potential consequences of affecting neurochemical homeostasis in the primary cortical control center for dopaminergic neurotransmission by downstream modifications and you can begin to grasp the wide-ranging effects of intentional receptor density modification -- and its possible consequences, such as anhedonia if downwards and dyskinesia if upwards. Also, epigenetic changes can occur that affect expression of VMAT2, and combining that with potential delta-FosB spikes, Ca2+/NMDA dysregulation, et.c., you can be looking at some unintended anxiogenic (or, if you're susceptible, manic, depressive, schizophrenic, psychotic, et.c.) effects from this experiment. Tread lightly, and slowly.

[normalizing]

cocaine is still the only and best dopamine booster i have had and i tried around 50 pills and herbs so i know. im just trying to figure out if its just the dopamine tho, maybe cocaine affects the NMDA system in some way? i cant find reliable info on this, but anyone has a clue, barbelith??

[Area-1255]

cocaine is still the only and best dopamine booster i have had and i tried around 50 pills and herbs so i know. im just trying to figure out if its just the dopamine tho, maybe cocaine affects the NMDA system in some way? i cant find reliable info on this, but anyone has a clue, barbelith??

Cocaine activates multiple pathways, it's a triple reuptake inhibitor - therefore it enhances norepinephrine and serotonin as well.

Norepinephrine is known to modulate dopamine and give a great energy burst in small-moderate amounts, it also contributes to "sensory euphoria".

[Multivitz]

Cocaine plays with the 'yes-no' pathway in the brain. This means in essence it disrupts the natural path of the brains energy. That means your brain has to expend energy putting it back to how it should be. Every drug that joins or touches a biological compound effectivly renders it useless after its ionic effect has worn off. The body then has to dispose of the spent compound, usually putting a massive strain on the immune system. If this was not the FACT then drugs would work, drugs seldom replace a fresh herb or fortified nutritional intake. If you want to raise L-dopa levels you have to raise Serotonin levels, unfortunately your body seeks homeostasis. Unless you have used vitamin D3 with adiquate nutrition and exercise you really have a narrow viewpoint on the subject of human growth. Its all about balance after you get the building materials inside. Use organic gold standard vitamin D3, steer clear of synthetics, and believe. Drugs are not infinite in their effect, natrure is. People get confused with the effect of dopamine, its usually a peak effect you feel as the Serotnin raises to balance with it! Check out my other posts for more info, thanks.

[HappyShoe]

Cocaine plays with the 'yes-no' pathway in the brain. This means in essence it disrupts the natural path of the brains energy. That means your brain has to expend energy putting it back to how it should be. Every drug that joins or touches a biological compound effectivly renders it useless after its ionic effect has worn off. The body then has to dispose of the spent compound, usually putting a massive strain on the immune system. If this was not the FACT then drugs would work, drugs seldom replace a fresh herb or fortified nutritional intake. If you want to raise L-dopa levels you have to raise Serotonin levels, unfortunately your body seeks homeostasis. Unless you have used vitamin D3 with adiquate nutrition and exercise you really have a narrow viewpoint on the subject of human growth. Its all about balance after you get the building materials inside. Use organic gold standard vitamin D3, steer clear of synthetics, and believe. Drugs are not infinite in their effect, natrure is. People get confused with the effect of dopamine, its usually a peak effect you feel as the Serotnin raises to balance with it! Check out my other posts for more info, thanks.

 

Isn't it typically the other way around, raising serotonin triggers dopamine cascades, at least in terms of pleasure/reward pathways?

Also, it's hard to take you seriously, when your username is Multivitz, and you're plugging 'organic gold standard' vitamin D3 and herbs/nutrients. Not that I'm against (some) use of nutrients and supplements, but you just sound like someone who came on this site to shamelessly con people into buying some product.

I feel obliged to mention that you disagreed without mentioning any references, used extremely vague terminology, and are just a 'tad off topic here as well.

 

Edited by HappyShoe, 07 February 2015 - 08:10 AM.

[normalizing]

anyone who comes here and keep discussing and recomending vitamin d is a quack. sick of those assholes and all those questionable studies on vitamin d. ive been taking gold, silver, bronze standard vitamin d forever in mega doses too, that shit didnt help prevent, heal or vaguely cause any benefit at all for years that if i see another asshole discussing, recomending it for whatever condition, ill slap em silly

[Area-1255]

 

Cocaine plays with the 'yes-no' pathway in the brain. This means in essence it disrupts the natural path of the brains energy. That means your brain has to expend energy putting it back to how it should be. Every drug that joins or touches a biological compound effectivly renders it useless after its ionic effect has worn off. The body then has to dispose of the spent compound, usually putting a massive strain on the immune system. If this was not the FACT then drugs would work, drugs seldom replace a fresh herb or fortified nutritional intake. If you want to raise L-dopa levels you have to raise Serotonin levels, unfortunately your body seeks homeostasis. Unless you have used vitamin D3 with adiquate nutrition and exercise you really have a narrow viewpoint on the subject of human growth. Its all about balance after you get the building materials inside. Use organic gold standard vitamin D3, steer clear of synthetics, and believe. Drugs are not infinite in their effect, natrure is. People get confused with the effect of dopamine, its usually a peak effect you feel as the Serotnin raises to balance with it! Check out my other posts for more info, thanks.

 

Isn't it typically the other way around, raising serotonin triggers dopamine cascades, at least in terms of pleasure/reward pathways?

Also, it's hard to take you seriously, when your username is Multivitz, and you're plugging 'organic gold standard' vitamin D3 and herbs/nutrients. Not that I'm against (some) use of nutrients and supplements, but you just sound like someone who came on this site to shamelessly con people into buying some product.

I feel obliged to mention that you disagreed without mentioning any references, used extremely vague terminology, and are just a 'tad off topic here as well.

 

Oh , wow, I'm just gonna LOVE this thread!

 

Let me  explain to you something very important (and don't worry , I will be writing an article on it soon)

 

It's not so simple as to say dopamine raises serotonin, or serotonin raises dopamine - but if you're gonna go with such an assumption - you should at least hear the ODDS THAT SEROTONIN WILL RAISE DOPAMINE ARE INCREDIBLY LOW!!!

 

• Dopamine inhibits dopamine at the D(2) receptors expressed as autoreceptors, whereas the post-synaptic D(2) receptors play a separate role in initiating endocrine responses and in controlling spasms and jerky movements.
•  
• Dopamine at D(2) and D(3) receptors interact with AMPA-glutamate pathway, and have secondary effects on GABA-ergic neurons.
•  
• Dopamine D(4) are similar to the two above, but may have a distinct or more specific action in depression and also on behavioral phenotypes.
•  
• Dopamine D(1) and dopamine D(5) stimulate locomotion (an indice of anti-depressant effects & general QOL scores) .

Now here's the biggest point to remember, no matter which neurotransmitter you are talking about. 

ALWAYS KNOW WHETHER THE RECEPTOR IS POSITIVELY OR NEGATIVELY COUPLED TO G-PROTEINS AND THUS ADENYLATE CYCLASE...

 

 

BECAUSE.....

 

If it's positively coupled it will have stimulatory effects and will increase basal and active metabolism as well as increase thyroid output and dopamine production. It will also signal HOMEOSTATIC mechanisms particularly signaling to serotonin 5-HT(1) autoreceptors to then decrease in moderation, the level of cAMP that was just increased...hence , this second messenger's all - important role in determining WHICH receptors get to handle the homeostatic feedback and partially determining the NET RATE of serotonin synthesis and activity. AKA that which is released in the blood stream or into the synapse BY THE MEANS of indirect autoreceptor activation that is the result of activating the conditional second messenger system of CYCLIC ADENOSINE MONOPHOSPHATE

 

If it's negatively coupled then we have an opposite array of effects, seeing instead of stimulation, we get depression, a decrease in dopamine synthesis and activity, and instead of 5-HT inhibitory signaling we get the potential CROSS-ACTIVATION of type 2 like serotonin receptors.

 

Additionally, those negatively coupled HAVE A TENDENCY to induce histamine and nitric oxide release, as well as GABA activity.

 

NOW LET'S GO BACK TO DOPAMINE AND SEROTONIN...IF YOU'VE ABSORBED THE ABOVE; then you're good!

 

Serotonin inhibits dopamine activity and release the type 1 receptors, as well as type 2, type 6 and type 5A receptors.

Whereas 5-HT3/4 have mixed effects , in some studies showing an enhancement in frontal lobe transmission, and in hippocampus mixed effects TRENDING WITH A DECREASE.

 

Therefore, all in all, there is a PROPENSITY & HIGHER LIKELIHOOD of serotonin to INHIBIT dopamine, than to raise it.

The NET effect of ANY neurotransmitter, especially MONOAMINES - is based on which receptors are available and the NET RATIO of heterodimized pairings and coincidentally, the ratio of NEGATIVE;POSITIVE FEEDBACK.

 

In other words, it simply comes down to more or less, if there is more positively coupled G-protein receptors being activated or more negatively coupled receptors being activated by premise or by consequence!

 

OR, IN EVEN SIMPLER TERMS....HOW MUCH CYCLIC AMP ONE HAS IS THE PRIMARY DETERMINANT TO TOTAL NERVOUS SYSTEM ACTIVITY AND THE BALANCE BETWEEN PARASYMPATHETIC AND SYMPATHETIC ACTIVITY THAT DETERMINES CENTRAL HOMESTASIS AND THUS THE PLAUSIBLE EXISTANCE OF DEPRESSIVE DISORDERS AND/OR THE TENDENCY TO SUCCUMB TO SUCH DISORDERS!

Edited by Area-1255, 07 February 2015 - 04:27 PM.

[AOLministrator]

@Area-1255:
I am not saying that any of this is is wrong, but do you really believe that your words will gain more power if you make them look like you are screaming and use other means of non-standard emphasis that seek to annoy the way in which other people perceive the world?

[Multivitz]

Yes I thought you would go for the bait (its low down way to get responses I know lol), of course Serotonin limits and lifts dopamine levels,  both use and respond to the same inhibitor enzyme. Balance needs to be understood in the BIO PATHWAYS,(absorbion of diet, individual requirements for raw materials), for the bennefits YOU guys are after. Calling a stranger an arsehole is kinda offensive, was my post offending you that much? Have you guys been battling for years against uneducated fools? Neurons compared to other cells in the body are Homeostatic masters, because of this fact the nervous system keeps us alive through environmental changes. There is Chi, it comes from the air we breath, it excites neurons. If you want to raise levels of your catecholamines what do you do, first you ask someone who has a high success in accompolishing this in themselves and others, and see what they are doing. A system that is close to a 100% is not unusual, people saying it is an impossible percentage is very common. The ones that get agressive and insulting are by their own actions DEPRESSED, depressed in there future assumptions of an individual, or frustration to their lack of real time practiced understanding of a subject. Either way they made actions to bring others down to thier level? When people say they have tried taking vitamins and other stuff.......it didn't work what they are really saying is that their body has such a long term deficiency, in what ever area, they have run out of patience morally and have taken on board negative assumptions that are told as incomplete positives i.e they are in a sea of information with others wanting to help.                          I have been battling fools for nealy 30 years, and talk to people as if they were here. The reason I recommended the D3 is that mega dosing does not work without massive diety support. D3 fuses minerals through the cell membrane, the cells use minerals for the production of Catecholamins. If there is ONE component missing, NOTHING of use happens. This is where the myth of megadosing comes from, its not needed, but can be used if you really DO know what you're doing. D3 is NOT A vitamin for crying out loud!! Read up on the stuff for a few DAYS to get the gist, then you may not be so damn ignorant

[Multivitz]

You guys may also be intrested in the full Serotonin cycle and how the Gi tract is heavily involved with it, instead of focusing on parts that are, for histories sake 'self regulating'? With healthy levels of Magnesium one is able to initiate a strong Ca+ cascade, this is how the central nervous system operates after all. All the Catecholamins do is act as semi conductors/electrical potential switches in the network of CNS, real drive for production comes from many sources not the manipulation of receptor sites. Poke 'em with a stick as much as you like, without adiquate building blocks nothing will happen except a shuffle of internal resources=a short term feeling something changed. Chemically indused brain damage is where the brain changes it's operation and structure because of it's environment, change the environment for the better and it starts to become whole again. Everything that passes ones lips, colours reflected on, skin contact, content of air breathed(rate of breathing), and state of emotions(driven by beliefs), internal flora, stored poisons(mineral, chemical) constitutes the internal environment. The bloodbrain barrier can tend to 'harden' in a harsh internal invironment, this makes treatment DIFFICULT for those who just focus on narrow  aspects of the  MASSIVLEY complex and interrelated bio chemical system that is us. The liver is very important for happiness, I find giving it a rest and clean helps, isn't vitamin D3 involved there too?? The reason I'm posting here is not because I'm a know nothing vitamin peddler, far from it, I'm posting here because I thought I'd do everyone a big favour and prevent you WASTING time. Sensations(physical and emotional) become blurred and strange with unnatural intervention. Once the tickle of highs meanders back to reality, over and over and over again, you'll soon realise after many attempts and many years, that I am profoundly right. We are all geniuses waiting to be freed, freed by our own choice of environment that works for us? And keeps working for all.                           Because of the interelation is so deep amongst biological pathways, a few things extra in the diet will NEVER work(be they drugs, hormones, vitamins, bio implants, happy faces, extra money, etc) to bring someone into health and keep them there. Unblocking a depressive state in someone is easy, getting the someone to understand the importance of their environment is next to impossible because of the cultural barriers of ignorance. Hence the 'shallow beliefs' bit in my profile! Glad to be of assistance. Please check out my other posts for more info.

Edited by Multivitz, 09 February 2015 - 06:10 PM.