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Browsing by Subject "GAD67"

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  • Mandelin, Ronja (2024)
    MDMA is an illegal stimulant known for its empathy-enhancing effects. Its positive effects are mainly based on increasing the concentrations of monoamines such as serotonin (5-HT), dopamine (DA) and norepinephrine (NE). In addition to its positive effects, MDMA can cause adverse effects such as hyperthermia and neurotoxicity. Especially with long-term use, MDMA can cause serotonergic and dopaminergic neurotoxicity. In addition, there are also indications of MDMA-induced neurotoxicity in systems where gamma-aminobutyric acid (GABA) functions as the main neurotransmitter. Glutamate decarboxylase (GAD) 67 is an enzyme that synthesizes GABA from glutamate and is a specific marker for GABAergic cells. The amygdala is a nucleus in the brain that regulates anxiety and fear response. In addition to GABAergic interneurons, there are also glutamatergic cells in the basolateral nucleus (BLA) of the amygdala, however in the central nucleus (CeA) there are only GABAergic cells. Disturbances in the GABAergic system can predispose to psychiatric diseases such as anxiety. The aim of thisstudy was to investigate the effects of MDMA (20 mg/kg) on the number of GAD67-positive cells in two nuclei of the mouse amygdala, BLA and CeA. In addition, this study aimed to examine the importance of the dose (4 or 16 injections) for neurotoxicity and the duration of the effects (2, 7 or 30 days). Adolescent wild type mice were divided into 12 groups according to the treatment (MDMA or saline), dose and timepoint. After euthanasia, the brain sections at the level of the amygdala were collected and stained with an immunohistochemical method and imaged using a confocal microscope. This study showed that MDMA reduced the number of GAD67-positive cells in the BLA when mice were given a total of 4 injections. This effect lasted up to 30 days. In contrast, MDMA did not reduce the number of GAD67-positive cells in the BLA in mice that were given 16 injections. Also, MDMA did not decrease the number of GAD67-positive cells in the CeA, regardless of dose. Statistical significance could have been improved, for example, by using more mice or analysing more sections from each individual animal. It is important to continue studying the effects of MDMA to better treat and prevent its adverse effects. In addition, increased understanding would urge users to exercise caution when using MDMA.