mdma glutamate

In recent years, studies with animal models of reward, such as the intracranial self-stimulation, self-administration, and conditioned place preference paradigms, have increased our knowledge on the neurochemical substrates of the rewarding effects of 3,4-methylenedioxymetamphetamine (MDMA) in rodents. However, pharmacological and neuroimaging studies with human participants are scarce. Serotonin [5-hydroxytryptamine (5-HT)], dopamine (DA), endocannabinoids, and endogenous opiates are the main neurotransmitter systems involved in the rewarding effects of MDMA in rodents, but other neurotransmitters such as glutamate, acetylcholine, adenosine, and neurotensin are also involved...

The interaction between MDMA and Nicotine affects multiple brain centres and neurotransmitter systems (serotonin, dopamine and glutamate) involved in motor coordination and cognition. In this study, we have elucidated the effect of prolonged (10 days) MDMA, Nicotine and a combined Nicotine-MDMA treatment on motor-cognitive neural functions. In addition, we have shown the correlation between the observed behavioural change and neural structural changes induced by these treatments in BALB/c mice. We observed that MDMA (2 mg/Kg body weight; subcutaneous) induced a decline in motor function, while Nicotine (2 mg/Kg body weight; subcutaneous) improved motor function in male periadolescent mice...

Some 3,4-methylenedioxymethamphetamine (MDMA) users become dependent as a result of chronic consumption. A greater understanding of the neurobiological basis of the rewarding effects of MDMA could contribute to developing effective pharmacotherapies for MDMA-related problems. The present study evaluated the role of N-methyl-D-aspartate (NMDA) glutamate receptors (NMDARs) in the acquisition and reinstatement of conditioned place preference (CPP) induced by MDMA. Adolescent male mice were conditioned with 1 or 10 mg/kg MDMA and pretreated with 5 or 10 mg/kg of the NMDAR antagonist memantine during acquisition of conditioning (experiment 1), or before a reinstatement test (experiment 2)...

MDMA is a widely abused psychostimulant which causes a rapid and robust release of the monoaminergic neurotransmitters dopamine and serotonin. Recently, it was shown that MDMA increases extracellular glutamate concentrations in the dorsal hippocampus, which is dependent on serotonin release and 5HT2A/2C receptor activation. The increased extracellular glutamate concentration coincides with a loss of parvalbumin-immunoreactive (PV-IR) interneurons of the dentate gyrus region. Given the known susceptibility of PV interneurons to excitotoxicity, we examined whether MDMA-induced increases in extracellular glutamate in the dentate gyrus are necessary for the loss of PV cells in rats...

Amphetamine-type psychostimulants (ATS) are used worldwide by millions of patients for several psychiatric disorders. Amphetamine (AMPH) and "ecstasy" (3,4-methylenedioxymethamphetamine or MDMA) are common drugs of abuse. The impact of chronic ATS exposure to neurons and brain aging is still undisclosed. Current neuronal culture paradigms are designed to access acute ATS toxicity. We report for the first time a model of chronic exposure to AMPH and MDMA using long-term rat cortical cultures. In two paradigms, ATS were applied to neurons at day 1 in vitro (DIV) (0, 1, 10 and 100 μM of each drug) up to 28 days (200 μM was applied to cultures up to 14 DIV)...

Kainic acid (KA) causes seizures and neuronal loss in the hippocampus. The present study investigated whether a recreational schedule of 3,4-methylenedioxymethamphetamine (MDMA) favours the development of a seizure state in a model of KA-induced epilepsy and potentiates the toxicity profile of KA (20 or 30mg/kg). Adolescent male C57BL/6 mice received saline or MDMA t.i.d. (s.c. every 3h), on 1day a week, for 4 consecutive weeks. Twenty-four hours after the last MDMA exposure, the animals were injected with saline or KA (20 or 30mg/kg)...

Schizophrenia pathophysiology is associated with alterations in several neurotransmitter systems, particularly dopamine, glutamate and serotonin (5-HT). Schizophrenia patients also have disruptions in sensory gating, a brain information filtering mechanism in response to repeated sensory stimuli. Dopamine and glutamate have been implicated in sensory gating; however, little is known about the contribution of serotonin. We therefore investigated the effects of several psychoactive compounds that alter serotonergic neuronal activity on event-related potentials (ERP) to paired auditory pulses...

OBJECTIVE: Ecstasy, or 3, 4 (±) methylenedioxymethamphetamine (MDMA), is a potent neurotoxic drug. One of the mechanisms for its toxicity is the secondary release of glutamate. Mouse embryonic stem cells (mESCs) express only one glutamate receptor, the metabotropic glutamate receptor 5 (mGlu5), which is involved in the maintenance and self-renewal of mESCs. This study aims to investigate whether MDMA could influence self-renewal via the mGlu5 receptor in mESCs. MATERIALS AND METHODS: In this expremental study, we used immunocytochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to determine the presence of the mGlu5 receptor in mESCs...

3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a popular drug of abuse with well-documented acute effects on serotonergic, dopaminergic, and cholinergic transmitter systems, as well as evidence of long-term disruption of serotoninergic systems in the rat brain. Recently, it was demonstrated that MDMA evokes a delayed and sustained increase in glutamate release in the hippocampus. The purpose of the present study was to determine the role of inflammatory mediators in the MDMA-induced increase in glutamate release, as well as the contribution of inflammatory pathways in the persistent neurochemical toxicity associated with repeated MDMA treatment...

3,4-Methylenedioxymethamphetamine (MDMA) is an illegal drug that can induce life-threatening hyperthermia. No effective pharmacological treatment for MDMA-induced hyperthermia has yet been established. We investigated the effects of memantine, a non-competitive N-methyl-D-aspartate (NMDA)-type glutamate receptor antagonist and an α-7 nicotinic acetylcholine receptor (nAChR) antagonist, on MDMA-induced hyperthermia in rats. Treatment of animals with memantine (10 or 20 mg/kg) either before or after MDMA (10 mg/kg) administration significantly decreased the peak body temperature...

The neurochemical effects of MDMA (3,4-methylenedioxymethamphetamine) on monoaminergic and cholinergic systems in the rat brain have been well documented. However, little is known regarding the effects of MDMA on glutamatergic systems in the brain. In the present study the effects of multiple injections of MDMA on extracellular concentrations of glutamate in the striatum, prefrontal cortex, and dorsal hippocampus were examined. Two or four, but not one, injections of MDMA (10 mg/kg, i.p. at 2 h intervals) resulted in a 2-3 fold increase in the extracellular concentration of glutamate in the hippocampus; no increase was evident in the striatum or prefrontal cortex...

Drug use typically occurs within a social context, and social factors play an important role in the initiation, maintenance and recovery from addictions. There is now accumulating evidence of an interaction between the neural substrates of affiliative behavior and those of drug reward, with a role for brain oxytocin systems in modulating acute and long-term drug effects. Early research in this field indicated that exogenous oxytocin administration can prevent development of tolerance to ethanol and opiates, the induction of stereotyped, hyperactive behavior by stimulants, and the withdrawal symptoms associated with sudden abstinence from drugs and alcohol...

MDMA (3,4-methylenedioxymethamphetamine) metabolism is a major cause of MDMA-mediated hepatotoxicity. In this study the effects of MDMA and its metabolites on the glutathione system were evaluated. Glutathione (GSH/GSSG) levels and gene expression of glutamate cysteine ligase catalytic subunit (GCLC), glutathione-S-transferase (GST) and pregnane X receptor (PXR) were compared in the immortalized human liver epithelial cell line THLE-Neo lacking phase I metabolism and primary rat hepatocytes expressing both phase I and II metabolism...

In animals, repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) reduces markers of serotonergic activity and studies show similar serotonergic deficits in human MDMA users. Using proton-magnetic resonance spectroscopy ((1)H-MRS) at 11.7Tesla, we measured the metabolic neurochemical profile in intact, discrete tissue punches taken from prefrontal cortex, anterior striatum, and hippocampus of rats administered MDMA (5mg/kg IP, 4× q 2h) or saline and euthanized 7 days after the last injection...

"Ecstasy" (MDMA) is a powerful hallucinogenic drug which has raised concern worldwide because of its high abuse liability. A plethora of studies have demonstrated that MDMA has the potential to induce neurotoxicity both in human and laboratory animals. Although research on MDMA has been carried out by many different laboratories, the mechanism underlying MDMA induced toxicity has not been fully elucidated. MDMA has the ability to reduce serotonin levels in terminals of axons in the cortex of rats and mice...

BACKGROUND AND PURPOSE: Recent experiments using non-selective 5-hydroxytryptamine (5-HT)(2C) receptor agonists including WAY 161503 suggested that midbrain 5-HT neurones are under the inhibitory control of 5-HT(2C) receptors, acting via neighbouring gamma-aminobutyric acid (GABA) neurones. The present study extended this pharmacological characterization by comparing the actions of WAY 161503 with the 5-HT(2C) receptor agonists, Ro 60-0275 and 1-(3-chlorophenyl) piperazine (mCPP), as well as the non-selective 5-HT agonist lysergic acid diethylamide (LSD) and the 5-HT releasing agent 3,4-methylenedioxymethamphetamine (MDMA)...

Methamphetamine (METH) is a major drug threat in the United States and worldwide. Monoclonal antibody (mAb) therapy for treating METH abuse is showing exciting promise and the understanding of how mAb structure relates to function will be essential for future development of these important therapies. We have determined crystal structures of a high affinity anti-(+)-METH therapeutic single chain antibody fragment (scFv6H4, K(D)= 10 nM) derived from one of our candidate mAb in complex with METH and the (+) stereoisomer of another abused drug, 3,4-methylenedioxymethamphetamine (MDMA), known by the street name "ecstasy...

Ecstasy, 3,4-methylenedioxymetamphetamine (MDMA), is a recreational drug used among adolescents, including young pregnant women. MDMA passes the placental barrier and may therefore influence fetal development. The aim was to investigate the direct effect of MDMA on cortical cells using dissociated CNS cortex of rat embryos, E17. The primary culture was exposed to a single dose of MDMA and collected 5 days later. MDMA caused a dramatic, dose-dependent (100 and 400 microM) decrease in nestin-positive stem cell density, as well as a significant reduction (400 microM) in NeuN-positive cells...

"Ecstasy" [(+/-)-3,4-methylenedioxymethamphetamine, MDMA, XTC, X, E] is a psychoactive recreational hallucinogenic substance and a major worldwide drug of abuse. Several reports raised the concern that MDMA has the ability to induce neurotoxic effects both in laboratory animals and humans. Despite more than two decades of research, the mechanisms by which MDMA is neurotoxic are still to be fully elucidated. MDMA induces serotonergic terminal loss in rats and also in some mice strains, but also a broader neuronal degeneration throughout several brain areas such as the cortex, hippocampus, and striatum...

Despite the potential for deleterious (even fatal) effects on cardiac physiology, 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) abuse abounds driven mainly by its euphoric effects. Acute exposure to MDMA has profound cardiovascular effects on blood pressure and heart rate in humans and animals. To determine the effects of MDMA on cardiac metabolites in rats, MDMA (0, 5, or 10 mg/kg) was injected every 2 h for a total of four injections; animals were sacrificed 2 h after the last injection (8 h drug exposure), and their hearts removed and tissue samples from left ventricular wall dissected...