6 replies to this topic

[InquilineKea]

Okay, so here are two journal articles I found.

Acute or repeated cocaine administration generates reactive oxygen species and induces antioxidant enzyme activity in dopaminergic rat brain structures

http://dx.doi.org/10...arm.2005.01.018

Cocaine Increases the Intracellular Calcium Concentration in Brain Independently of Its Cerebrovascular Effects

http://www.jneurosci...act/26/45/11522


And a couple more:

13. Zaragoza A, Diez-Fernandez C, Alvarez AM, Andres D, Cascales
M (2000) Effect of N-acetylcysteine and deferoxamine on
endogenous antioxidant defense system gene expression in a rat
hepatocyte model of cocaine cytotoxicity. Biochim Biophys Acta
1496:183–195
14. Boess F, Ndikum-Moffor FM, Boeslsterli UA, Roberts SM
(2000) Effects of cocaine and its oxidative metabolites on mito-
chondrial respiration and generation of reactive oxygen species.
Biochem Pharmacol 60:615–623


At the same time, I see many other journal articles saying that cocaine does not cause a long-term depletion in dopamine (or dopamine receptors) for cocaine abusers. I've tried to really look into things, and the general observation seems to be that cocaine is not neurotoxic, whereas amphetamine is. Yet, the above articles seem to indicate a route for cocaine neurotoxicity. Does cocaine just prevent its own neurotoxicity by also inducing antioxidant enzyme activity (as mentioned above)? This gives me some hope that I might be able to prevent Adderall-induced neurotoxicity, maybe. BUT, long-term damage to dopamine neuron axons is *independent* of ROS damage, and ROS damage can occur even without the damage of dopamine neuron axons.

==

And then from another paper (Attenuation of Cocaine and Methamphetamine Neurotoxicity
by Coenzyme Q 10):

Repeated
cocaine or METH treatment induced significant reductions
in the striatal DA and CoQ 10 . Repeated METH treatment
was more deleterious on the NS DA-ergic system as com-
pared to repeated cocaine treatment. This was evident by
relatively more reduction in the DA and significantly
reduced CoQ 10 in repeated METH-treated mice as
compared to repeated cocaine-treated mice. Significant
reduction in the striatal CoQ 10 in repeated cocaine or
METH-treated mice would suggest that these drugs induce
mitochondrial damage by inhibiting oxidative phosphory-
lation. CoQ 10 provides neuroprotection by augmenting
complex I and by inhibiting NFjb induction in aging
homozygous weaver mutant (wv/wv) mice [8] and in
rotenone-treated SK-N-SH cells

Edited by inquilinekea, 09 January 2011 - 09:37 AM.

[aLurker]

Well, the spectacularly nefarious cardiovascular effects in combination with the addictiveness make avoiding cocaine a no-brainer either way. If you still want to know how it affects dopamine you could ask the people over at bluelight. Personally I'm not interested since I'm busy not having a heart attack.

Edited by aLurker, 09 January 2011 - 09:45 AM.

[InquilineKea]

Well yeah, I'm avoiding cocaine either way. The reason I'm asking this is this: if cocaine increases antioxidant amounts (by itself), preventing any real cocaine-induced damage, then maybe we can do the same for Adderall (by taking supplements). And it appears to be true.

As judged from the measurement of caspase-3 activity and TUNEL labeling, neither acute nor chronic
cocaine treatment has been found to induce apoptosis in any of the structures examined. This differs dramatically from what has been
described for methamphetamine. Cocaine-induced radical formation was accompanied by the induction of the antioxidant enzymes
superoxide dismutase and glutathione peroxidase, after both acute and chronic cocaine treatment. In addition, proteasome
chymotrypsin-like activity was enhanced following a single cocaine injection in both cortex and striatum. It is proposed that the
compensatory mechanisms to oxidative stress occurring in response to cocaine were effective in scavenging reactive oxygen species
and in preventing subsequent cellular damage, thus explaining why no significant cell death was found in these brain structures.

Edited by inquilinekea, 09 January 2011 - 09:58 AM.

[tjcbs]

you are concerned with adderall neurotoxicity, and you are researching cocaine? that makes no sense. Amphetamine neurotoxicity is well known. It seems like dopamine re-update inhibitors(cocaine, ritalin) are much less neurotoxic than releasers (amphetamines).

[InquilineKea]

you are concerned with adderall neurotoxicity, and you are researching cocaine? that makes no sense. Amphetamine neurotoxicity is well known. It seems like dopamine re-update inhibitors(cocaine, ritalin) are much less neurotoxic than releasers (amphetamines).

I *know* that they are different in some ways. But researching cocaine would still be useful because both amphetamines and cocaine share some similar neurotoxic routes with each other. I'm just trying to see which routes are less neurotoxic than others (the ones they share are probably less neurotoxic than the ones unique to amphetamines - apparently the major difference lies in how they both interact with VMAT-2 and synaptic vesicles)

[VoidPointer]

you are concerned with adderall neurotoxicity, and you are researching cocaine? that makes no sense. Amphetamine neurotoxicity is well known. It seems like dopamine re-update inhibitors(cocaine, ritalin) are much less neurotoxic than releasers (amphetamines).

I *know* that they are different in some ways. But researching cocaine would still be useful because both amphetamines and cocaine share some similar neurotoxic routes with each other. I'm just trying to see which routes are less neurotoxic than others (the ones they share are probably less neurotoxic than the ones unique to amphetamines - apparently the major difference lies in how they both interact with VMAT-2 and synaptic vesicles)

prove this statement

amphetamines and cocaine share some similar neurotoxic routes with each other

Also there are some major differences between methylphenidate and cocaine.

Key Difference between methylphenidate and cocaine: Rate of clearance from the striatum region of the brain: As mentioned in an earlier post, the addiction potential of a drug is typically correlated to the rate of exit or clearance from the brain. In other words, drugs that linger in the brain's receptors for extended periods of time are often much less addicting than ones which exhibit a short and rapid spike in their brain levels and then a quick drop-off in their concentration in the brain. In the striatum, the rate of clearance takes about 90 minutes for methylphenidate, and only 20 minutes for cocaine. If we go by peak concentration duration (i.e. the amount of time the highest concentration typically lasts in the brain before going back down), we see that methylphenidate's peak lasts around 15 to 20 minutes, while cocaine's is a fleeting 2 to 4 minutes. In both cases, the higher dissipation of the drug from high levels in the brain is much more pronounced in cocaine, giving this drug a much more addiction-worthy effect over methylphenidate (even when methylphenidate is abuses and either snorted or injected, it still cannot match the rates of clearance of cocaine).

when methylphenidate, such as Ritalin, Concerta or Metadate is taken orally, this nucleus accumbens region is not targeted (at least not anywhere near the level of injection).

The nucleus accumbens is believed to play an important role in the addiction potential of a number of drugs, including many stimulant medications. Thus, proper use of the methylphenidate medication actually bypasses a key brain region believed to be critically involved in the "high" or addiction process of a stimulant drug. This highlights a major difference in the pharmacology between Ritalin and cocaine.

[InquilineKea]

prove this statement

"Acute or repeated cocaine administration generates reactive oxygen species and induces antioxidant enzyme activity in dopaminergic rat brain structures"

That's the title of a paper. My point, anyways, is that cocaine neurotoxicity (in one way) is largely alleviated because cocaine upregulates BOTH oxidants and antioxidants (I'm assuming that both cocaine and amphetamines exert this same type of neurotoxicity for now [amphetamines have other routes too], although I could be wrong on that). Since amphetamines *don't* upregulate these antioxidants too, it results in a neurotoxicity that cocaine doesn't have (and this is the type of neurotoxicity that results in lipid perioxidation, or the one that damages mitochondria). Of course, this isn't the only type of neurotoxicity in amphetamines, but it shows that amphetamine neurotoxicity is more than just the damage of dopaminergic axon terminals. But it's helpful knowing all of the different routes of amphetamine neurotoxicity.

Also there are some major differences between methylphenidate and cocaine.

Key Difference between methylphenidate and cocaine: Rate of clearance from the striatum region of the brain: As mentioned in an earlier post, the addiction potential of a drug is typically correlated to the rate of exit or clearance from the brain. In other words, drugs that linger in the brain's receptors for extended periods of time are often much less addicting than ones which exhibit a short and rapid spike in their brain levels and then a quick drop-off in their concentration in the brain. In the striatum, the rate of clearance takes about 90 minutes for methylphenidate, and only 20 minutes for cocaine. If we go by peak concentration duration (i.e. the amount of time the highest concentration typically lasts in the brain before going back down), we see that methylphenidate's peak lasts around 15 to 20 minutes, while cocaine's is a fleeting 2 to 4 minutes. In both cases, the higher dissipation of the drug from high levels in the brain is much more pronounced in cocaine, giving this drug a much more addiction-worthy effect over methylphenidate (even when methylphenidate is abuses and either snorted or injected, it still cannot match the rates of clearance of cocaine).

when methylphenidate, such as Ritalin, Concerta or Metadate is taken orally, this nucleus accumbens region is not targeted (at least not anywhere near the level of injection).

The nucleus accumbens is believed to play an important role in the addiction potential of a number of drugs, including many stimulant medications. Thus, proper use of the methylphenidate medication actually bypasses a key brain region believed to be critically involved in the "high" or addiction process of a stimulant drug. This highlights a major difference in the pharmacology between Ritalin and cocaine.

That's definitely a good point, and I appreciated that (since I've now made the decision to finally switch to methylphenidate). That has to do with addiction potential, which is independent of neurotoxicity.

Edited by InquilineKea, 11 January 2011 - 05:09 AM.