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Thread: Does Klonopin Effect Dopamine?

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    Does Klonopin Effect Dopamine? 
    #1
    This question might be too broad, but does anyone know?
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    #2
    Bluelight Crew nAON's Avatar
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    Pretty sure it doesn't.
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    #3
    Bluelighter Swimmingdancer's Avatar
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    This study says clonazepam (Klonopin) had no effect on dopamine release. http://www.ncbi.nlm.nih.gov/m/pubmed/1658299/

    However the studies on if/how different benzos affect dopamine appear to have conflicting results.
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    #4
    Bluelighter hatrix's Avatar
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    I would assume it has zero affect on dopamine. Didn't read the study swimmingdancer posted, but I'm sure that's conformation enough.
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    #5
    Bluelighter synthetix's Avatar
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    Don't all benzos have a slight antagonistic effect on dopamine levels due to the increased amount of GABA that's made readily available, and the same for serotonin too? Though this is an indirect mechanism it still does play a part in it.
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    #6
    If you suffer from anxiety, there's definitely a release of DA in the reward pathway, even if its just psychological.

    As far as direct DA effects, alprazolam is the only benzo that demonstrates increased locomotor activity in rats. In all likelihood, this is probably why Xanax is coveted as the most addictive and hardest to withdrawl from.
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    #7
    Bluelighter synthetix's Avatar
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    Tuss id really like to see that study. As far as I'm aware alprazolam is only the most addictive due to its short half life, therefore it encourages compulsive redosing as you start to feel a lot of rebound anxiety if you've missed a dose or have passed its peak plasma concentrations in your blood and you're GABA levels are depleting. The same goes for triazolam (which incidentally is where alprazolam is linked to) - which is considered to be even more addictive than alprazolam perhaps due to its ridiculously short half life but perhaps other mechanisms too.
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    #8
    Eur Neuropsychopharmacol. 2001 Feb;11(1):41-50.
    Role of dopaminergic and serotonergic systems on behavioral stimulatory effects of low-dose alprazolam and lorazepam.

    Abstract
    Several recent studies have demonstrated that alprazolam and lorazepam, administered at low doses to healthy volunteers, improve cognitive functions and psychomotor performances. Paradoxical effects of low-dose benzodiazepines have been also observed in mice, in experimental pharmacology. The aim of this work was to determine, in rat, the effect of similar low-doses of benzodiazepines on spontaneous locomotor activity and performance in the elevated zero-maze, and to investigate the underlying neurobiological mechanisms. The dose-effect and the time-course of the action were studied for both compounds. Spontaneous locomotor activity was measured using a photoelectric actimeter. The level of anxiety of the animals was assessed in the elevated zero-maze. Dopamine, serotonin, and their metabolites were assayed in the extracellular striatal fluid of the awake rat, obtained by microdialysis, by HPLC--EC. Spontaneous locomotor activity observed in rats given low-dose alprazolam and lorazepam evidenced a stimulatory effect only with alprazolam. The effect was maximum 90 min after administration of 0.0050 mg/kg alprazolam. An anxiogenic-like action was evidenced with the elevated zero-maze for the two compounds. We observed a statistically significant increase in striatal dopamine concentrations only with alprazolam, during the period corresponding to the behavioral stimulatory effects. We also showed a marked trend towards increased levels of serotonin with alprazolam but this modification was not significant, in spite of statistically significant variations of 5-HIAA. In the rat, behavioral stimulatory effects of low-dose benzodiazepines is evidenced with alprazolam but not lorazepam. This effect could be explained, at least in part, by increased extracellular dopamine concentrations in the striatum. Their different structures could explain the different pattern observed for the two benzodiazepines.
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    #9
    Bluelighter Swimmingdancer's Avatar
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    ^That doesn't say alprazolam is the only benzo that (potentially) does that, it's only comparing it to lorazepam.

    Quote Originally Posted by synthetix View Post
    Don't all benzos have a slight antagonistic effect on dopamine levels due to the increased amount of GABA that's made readily available, and the same for serotonin too? Though this is an indirect mechanism it still does play a part in it.
    I know, that's what I thought too, but the studies say some benzos inhibit dopamine, some don't affect it, and some increase it, strangely.

    For example, that study I posted the link for above says:
    - diazepam inhibited dopamine release
    - Ro 5-4864 (a peripheral benzo) also inhibited dopamine release
    - PK 11195, considered a peripheral benzo receptor antagonist, didn't block the inhibition induced by diazepam, but rather inhibited dopamine release itself
    - clonazepam did not affect dopamine release
    - Ro 15-1788 (a centrally acting benzo) did not affect dopamine release

    It also says the inhibitory action of the ones that inhibited dopamine was likely "mediated through one type of peripheral-type benzodiazepine receptors which are coupled to voltage-gated Ca++ channels and that these receptors may not necessarily be the same as those in other tissues".

    On the other hand, The National Institute on Drug Abuse (NIDA) a US federal government research institute, (whose research I don't always trust), says:

    Benzodiazepines weaken the influence of a group of cells, called inhibitory interneurons, in the brain’s ventral tegmental area (VTA). These neurons normally help prevent excessive dopamine levels by downregulating the firing rates of dopamine-producing neurons. Two negatives make a positive, so when benzodiazepines limit the interneurons’ restraining influence, the dopamine-producing neurons release more dopamine.
    More on that can be found here: Well-Known Mechanism Underlies Benzodiazepines' Addictive Properties
    BUT, even though they are saying it applies to all benzos it looks like midazolam was the only one studied.
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    #10
    Bluelighter
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    I remember reading some where on here that GABA is responsible for controlling the realeases of other brain chemicals such as dopamine, serotonin etc ???
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    #11
    Quote Originally Posted by Jakeperson View Post
    I remember reading some where on here that GABA is responsible for controlling the realeases of other brain chemicals such as dopamine, serotonin etc ???
    Yeah, I thought most people would comment that it inhibited dopamine release. If people use it to comedown from meth, wouldn't it have to inhibit dopamine in some way?
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    #12
    Bluelighter Swimmingdancer's Avatar
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    Yeah you would think it would at least indirectly lessen the effects of dopamine and other neurotransmitters by increasing the effects of GABA. As I said, the studies are confusing and contradictory. I will look into it more, since it seems strange to me too.
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