Nadh
lenses said:
Personally I find Gabapentin and some sort of dopamine supplement like L-tyrosine or L-dopa (can be found in stores as Macuna plant extracts) to help. A lot of the things named are difficult to find.
Coke craving are a result of lowered dopamine levels.Give it about 3 days and you'll be better. Eats lots of protein and your veggies. Believe me i've been through this a lot...
Oh also, theres a supplement called NADH which supposedly raises tyrosine hydroxylase levels through some goofy way. I've been using it and feeling heaps better.
Pm me if you really need help...
All I know:
1) Stimulants activate cAMP.
2) Genes for the following are (somehow) regulated by cAMP:
Tyrosine hydroxylase, prodynorphin, somatostatin and proenkephalin.
3) NADH and cAMP both are (somehow) involved in allosterical regulation that (somehow) determine (some) enzymatic function.
Really - that is all I know!
Anyone willing to venture a hypothesis?
This is what I could find on NADH and cocaine:
Neuroreport. 1997 Jul 28;-41.
Cocaine self-administration alters brain NADH dehydrogenase mRNA levels.
Couceyro P, Shoaib M, McCoy M, Goldberg SR, Kuhar MJ.
Division of Neuroscience, Yerkes Regional Primate Center, Emory University, Atlanta, GA 30329, USA.
Using differential display PCR, we identified a cDNA whose expression is altered in several brain regions in rats self-administering cocaine. The cDNA sequence corresponds to bases 13687-13723 of the rat NADH dehydrogenase subunit 6 gene. Northern analysis indicated a 26% decrease in nucleus accumbens, a 305% increase in the ventral midbrain and no changes in the caudate putamen mRNA levels; changes were also noted in the hypothalamus and cerebellum. This is the first demonstration of an effect of cocaine self-administration on mitochondrial gene expression and suggests that regional metabolic changes elicited by cocaine may be relevant to and involved in its reinforcing properties.
PMID: 9261805 [PubMed - indexed for MEDLINE]
Related Links
* NAC-1, a rat brain mRNA, is increased in the nucleus accumbens three weeks after chronic cocaine self-administration. [J Neurosci. 1997]
* Chronic intracerebroventricular cocaine differentially affects prodynorphin gene expression in rat hypothalamus and caudate-putamen. [Brain Res Mol Brain Res. 1996]
* Differential expression of mitochondrial NADH dehydrogenase in ethanol-treated rat brain: revealed by differential display. [Alcohol Clin Exp Res. 1997]
* PCR differential display identifies a rat brain mRNA that is transcriptionally regulated by cocaine and amphetamine. [J Neurosci. 1995]
* Expression of c-fos, NGFI-A and secretogranin II mRNA in brain regions during initiation of cocaine self-administration in mice. [Eur J Neurosci. 1999]
2: Ann N Y Acad Sci. 2004 Oct;1025:345-50.Click here to read Compound (MeSH Keyword), Substance (MeSH Keyword), LinkOut
Cocaine downregulates the expression of the mitochondrial genome in rat brain.
Dietrich JB, Poirier R, Aunis D, Zwiller J.
INSERM U 575, Centre de Neurochimie, 67084 Strasbourg, France.
[email protected]
Analysis by differential display of genes induced in response to acute cocaine administration to rats revealed the significant downregulation of several mitochondrial genes in the cingulate cortex, including the subunits 1, 2, 4, 5, and 6 of NADH dehydrogenase and the subunit 2 of cytochrome c oxidase. Although the mechanism of the downregulation of expression of these mitochondrial genes by cocaine is presently not well understood, one can envisage that it involves an increased production of reactive oxygen species in cells of the cerebral cortex.
PMID: 15542735 [PubMed - indexed for MEDLINE]
Related Links
* Distinct gene expression profiles in adult rat brains after acute MK-801 and cocaine treatments. [Eur Neuropsychopharmacol. 2006]
* Cocaine-induced expression changes of axon guidance molecules in the adult rat brain. [Mol Cell Neurosci. 2005]
* The anesthetics propofol and ketamine inhibit cocaine-induced egr-1 gene expression in rat forebrain. [Eur J Pharmacol. 2002]
* Time-course of mitochondrial gene expressions in mice brains: implications for mitochondrial dysfunction, oxidative damage, and cytochrome c in aging. [J Neurochem. 2005]
3: J Pharmacol Exp Ther. 1989 Oct;251(1):258-66.Click here to read Compound (MeSH Keyword), Substance (MeSH Keyword), LinkOut
Attenuation by dopamine uptake blockers of the inhibitory effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and some of its analogs on NADH-linked metabolism in mouse neostriatal slices.
Ofori S, Heikkila RE, Nicklas WJ.
Department of Neurology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway.
In previous studies it was shown that the pyridinium species formed by the monoamine-oxidase-catalyzed conversion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-(2'methylphenyl)-1,2,3,6-tetrahydropyridine (2'Me-MPTP) inhibited mitochondrial electron transport at Complex I. In addition, these substances, when incubated with mouse neostriatal slices, caused an increased lactate accumulation. However, it was not clear whether this inhibition could occur within dopamine nerve terminals. In the present study we investigated if dopamine uptake blockers, shown previously to protect against tetrahydropyridine-induced dopaminergic neurotoxicity, would attenuate MPTP- and 2'Me-MPTP-promoted lactate formation in neostriatal slices. 2'Me-MPTP-induced lactate accumulation in neostriatal slices from mice or rats with a lesion of the nigrostriatal pathway was also studied. The dopamine uptake blocker, Win 35,428 [8-azabicyclo[3.2.1]octane-2-carboxylic acid, 3-(4-fluorophenyl)-8-methyl-, methylester [1R-(exo, exol)]), attenuated the increased lactate formation caused by MPTP and 2'Me-MPTP. At low concentrations of 2'Me-MPTP (5 microM), the increased lactate production was inhibited completely by Win 35,428. These latter data suggest that at low concentrations of 2'Me-MPTP, the increased lactate accumulation was associated primarily with dopaminergic nerve terminals. Two other dopamine uptake inhibitors, McN 5908 [trans-4-(1,2,3,5,6,10b-hexahydropyrrolo[2,1-alpha]isoquinolin+ ++-6-yl) benzenamine hydrobromide methanolate (4:4:1)] and mazindol [5-(4-chlorophenyl)-2,5-dihydro-3H-imidazo- [2,1-alpha]isoindol-5-ol], also attenuated tetrahydropyridine-induced lactate formation. At concentrations selective for their respective uptake systems, norepinephrine- and serotonin-uptake inhibitors did not attenuate 2'Me-MPTP-induced lactate accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
PMID: 2571719 [PubMed - indexed for MEDLINE]
Related Links
* Role for monoamine oxidase-A (MAO-A) in the bioactivation and nigrostriatal dopaminergic neurotoxicity of the MPTP analog, 2'Me-MPTP. [Eur J Pharmacol. 1988]
* Prevention of the nigrostriatal toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by inhibitors of 3,4-dihydroxyphenylethylamine transport. [J Neurochem. 1986]
* Mitochondrial and metabolic toxicity of 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine. [J Pharmacol Exp Ther. 1987]
* Protection against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine by monoamine oxidase inhibitors. [Nature. 1984]
* Studies on the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: inhibition of NAD-linked substrate oxidation by its metabolite, 1-methyl-4-phenylpyridinium. [J Neurochem. 1986]
4: Res Commun Chem Pathol Pharmacol. 1973 Jan;5(1):237-40.Compound (MeSH Keyword), Substance (MeSH Keyword), LinkOut
Inhibitory effect of certain drugs on NADH dehydrogenase of mouse heart homogenates.
Zwarenstein H, Sapeika N.
PMID: 4405565 [PubMed - indexed for MEDLINE]
Related Links
* Inhibitory effect of fenfluramine and propranolol on NADH dehydrogenase of mouse heart homogenates. [Res Commun Chem Pathol Pharmacol. 1972]
* Inhibitory effect of anti-obesity drugs on NADH dehydrogenase of mouse heart homogenates. [Res Commun Chem Pathol Pharmacol. 1975]
* Effect of a norfenfluramine derivative (S780) on NADH dehydrogenase and on certain other enzymes of mouse tissue homogenates. [Res Commun Chem Pathol Pharmacol. 1973]
* The effect of inhibitors on the electron-transport chain of Bacillus brevis. Evidence for branching of the NADH oxidase respiratory chain. [J Gen Microbiol. 1974]
* Patterns of cytochrome oxidase inhibition by polycations. [J Bioenerg. 1973]
