Methylenedioxymethamphetamine (Ecstasy) Decreases Neutrophil Activity and Alters Leukocyte Distribution in Bone Marrow, Spleen and Blood

Abstract

Objective: Looking for possible neuroimmune relationships, we analyzed the effects of methylenedioxymethamphetamine (MDMA) administration on neuroendocrine, neutrophil activity and leukocyte distribution in mice. Methods: Five experiments were performed. In the first, mice were treated with MDMA (10 mg/kg) 30, 60 min and 24 h prior to blood sample collection for neutrophil activity analysis. In the second experiment, the blood of naïve mice was collected and incubated with MDMA for neutrophil activity in vitro analysis. In the third and fourth experiments, mice were injected with MDMA (10 mg/kg) and 60 min later, blood and brain were collected to analyze corticosterone serum levels and hypothalamic noradrenaline (NA) levels and turnover. In the last experiment, mice were injected with MDMA 10 mg/kg and 60 min later, blood, bone marrow and spleen were collected for leukocyte distribution analysis. Results: Results showed an increase in hypothalamic NA turnover and corticosterone serum levels 60 min after MDMA (10 mg/kg) administration, a decrease in peripheral blood neutrophil oxidative burst and a decrease in the percentage and intensity of neutrophil phagocytosis. It was further found that MDMA (10 mg/kg) treatment also altered leukocyte distribution in blood, bone marrow and spleen. In addition, no effects were observed for MDMA after in vitro exposure both in neutrophil oxidative burst and phagocytosis. Conclusion: The effects of MDMA administration (10 mg/kg) on neutrophil activity and leukocyte distribution might have been induced indirectly through noradrenergic neurons and/or hypothalamic-pituitary-adrenal axis activations.

Ecstasy induces reactive oxygen species, kidney water absorption and rhabdomyolysis in normal rats. Effect of N-acetylcysteine and Allopurinol in oxidative stress and muscle fiber damage

“…This time was chosen to simulate the high Ec ingestion that usually occurs at raves and parties, which in many cases, induces severe alterations in hydroelectrolyte metabolism and tissue damage, causing high lethality [26,27,28,29,30]. …”

3,4-Methylenedioxymethamphetamine (Ecstasy) Decreases Inflammation and Airway Reactivity in a Murine Model of Asthma

“…We have shown that MDMA (10 mg/kg) increased HPA axis activity, as shown by an increase in serum levels of corticosterone, probably through the activation of the noradrenergic pathway in the hypothalamus [11]. The increase in corticosterone serum levels persisted up to 6 h after MDMA treatment (online suppl.…”

“…MDMA (99% pure) was dissolved in a 0.9% NaCl solution to a concentration of 10 mg/kg. MDMA or 0.9% saline was administered by intraperitoneal injection at a volume of 0.1 ml/10 g. The MDMA dose was chosen based on a previous experiment conducted in our laboratory [11]. Mifepristone (RU 486; Tocris Bioscience, Ellisville, Mo., USA), a glucocorticoid receptor GRII antagonist, was dissolved in PEG-400 to a concentration of 5 mg/ml and administered by subcutaneous injection of 100 µl/mouse.…”

“…MDMA is also known for its enpathogenic euphoria and its ability to increase energy and sexual arousal [3], which leads to an enhanced response to sensory stimulation [4,5,6]. Moreover, it has been reported that MDMA induces hyperthermia, increases heart rate, anxiety [7], neurodegeneration of serotonergic [8] and catecholaminergic pathways [9,10], and induces hypothalamo-pituitary-adrenal (HPA) axis activation [11] and immunological alterations [11,12]. …”

“…Recently, we showed that MDMA decreases neutrophil activity and alters leukocyte distribution [11]. MDMA decreased the neutrophil oxidative burst and phagocytosis, increased the number of circulating neutrophils while decreasing the number of lymphocytes.…”