Wednesday, June 6, 2007

Tiffany's Seminar

The scientific study that I read about is Serotonergic Neurotoxic Metabolites of Ecstasy Identified in Rat Brain. It is testing how ecstasy (MDMA) causes a neurotoxic effect in rats. A neurotoxic effect is the behavioral change in an organism that originates from a toxin that damages or destroys nerve tissue.

Ecstasy will not cause a neurotoxic effect in rats by direct injection into the brain, rather, it must be metabolized and detoxified through the liver. But as MDMA is detoxified by the liver, the process produces metabolites that are detrimental to the brain—it contributes to neurotoxic effects.

The experiment detects decreases in brain function with the neurotransmitter serotonin. By measuring the levels of serotonin in the brain, if there is a drop of serotonin in the brain, there is an increase of GSH metabolite in the brain, which contributes to neurotoxicity.

In showing that MDMA neurotoxicity depends on the metabolism of the MDMA, rather than the MDMA itself, we want to simulate the process in rats.

The study first synthesizes the metabolites that would be produced in the liver, since previous data seems to indicate that these metabolites cause the neurotoxicity.

Next, the surgery is conducted on the rats to expose the brain, more specifically, the striatum of the brain.

Before injection of the metabolites is begun, (explain blood brain barrier).

Acivicin is used to inhibit gamma-GT. Acivicin is an enzyme that inhibits gamma-GT, which is the blood brain barrier. The BBB is the brain endothelial cell, and it protects the brain from being exposed to any foreign substances and sends these foreign substances to other parts of the body, where they will be excreted.

In order to allow metabolites to enter the brain, gamma-GT, or the blood brain barrier, must be inhibited by the enzyme acivicin. Acivicin is used to enhance the delivery of these metabolites into the brain to simulate prolonged ecstasy use in the body.

In this way, GSH metabolites are able to pass the blood brain barrier and accumulate in the brain.

Results: Metabolites are present in the striatum of rats when MDMA was injected subcutaneously (under the skin) of rats. With specialized analysis, the neurotoxic metabolites were identified in the brain of the animal for the first time. But it is still unclear as to the mechanism for the metabolites produce neurotoxicity.

The purpose of this experiment is to later on connect this research with neurotoxic effects and the effects of chronic exposure of ecstasy (MDMA) on humans.

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