GHB en serotonine?

Einstein schreef:Het verhoogt juist de aanmaak van nieuwe serotonine, doordat het transport van tryptofaan, waaruit serotonine wordt gemaakt, wordt gestimuleerd. De tolerantie van MDMA wordt echter niet veroorzaakt door een tekort aan serotonine, maar door veranderde zenuwverbindingen, ik weet niet wat voor effect GHB hierop heeft. Ik zou gokken dat het niet al te veel invloed op je MDMA-tolerantie heeft, maar weet het dus niet zeker.

Our preliminary data indicate that neuroendocrine responses to MDMA are uniformly blunted in rats previously exposed to the drug, in agreement with findings in human Ecstasy users (Gerra et al., 1998, Gerra et al., 2000, Verkes et al., 2001). Importantly, tolerance to the subjective effects of MDMA is a common complaint in human drug users and has been implicated in dangerous dose escalation (Verheyden et al., 2003, Parrott, 2005).

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It is well established that MDMA administration to laboratory animals causes deficits in 5-HT neurons (e.g., depletion of brain tissue 5-HT), but the functional significance and clinical relevance of such changes are less clear (Easton and Marsden, 2006, Baumann et al., 2007).

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Interestingly, human MDMA users are reported to display attenuated hormone responses to the 5-HT releaser d-fenfluramine, and this reduced sensitivity can last for months after abstinence (Gerra et al., 1998, Gerra et al., 2000, Verkes et al., 2001).

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Collectively, the data suggest that tolerance to neuroendocrine effects of MDMA is due to impairments in SERT-mediated release of 5-HT from nerve terminals in the brain. Our findings could have implications for human MDMA users who often report the development of tolerance to subjective effects after prolonged use (Verheyden et al., 2003, Parrott, 2005).

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The ability of low-dose MDMA to preferentially increase dialysate 5-HT supports the predominant role of serotonergic mechanisms in mediating stimulus properties of MDMA (Schechter, 1988, Goodwin et al., 2003).

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Our results suggest that MDMA tolerance in humans may reflect 5-HT deficits which could contribute to further dose escalation.

Serotonin contents of the three regions investigated do not change significantly, except after NCS-356 treatment, which induces a slight decrease in the frontal cortex and the striatum, accompanied by an even more pronounced decrease in the hippocampus. The absence of serotonin increase may be due to rapid intracellular metabolism of serotonin after potentiation of its synthesis. 5-HIAA is an index of the rate of serotonin metabolism in tissue because a decrease in the extracellular concentration of serotonin was seen after GHB treatment

The subjective experienced effects of GHB during MDMA intoxication might also be explained by GHB’s effect on 5-HT synthesis. MDMA induces an acute release of 5-HT and DA. The acute release is followed by a depletion of intraneural 5-HT stores. GHB increases the availability of 5-hydroxytryptophan, the precursors of 5-HT, and potentiates the serotonin turnover in certain brain areas [68]. In this way, GHB might temporarily complete the 5-HT in the presynaptic neurone that has been dispelled by MDMA. Furthermore, there is evidence that GHB itself releases 5-HT; however, it is dependent on the amount of serotonin that is presynaptically available, and thus on the amount of MDMA that has been taken.

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In humans, an increased dopamine release in the striatum stimulates uncontrollable locomotor activities expressed by jaw clenching (bruxism) and motor restlessness, effects that might be reduced by GHB.