Pharmacodynamic interactions between MDMA and concomitants in MDMA tablets on extracellular dopamine and serotonin in the rat brain

Abstract

Baseline levels of dopamine and 5-HT in the striatum were 16.5±7.7 and 3.5±1.7 nM (mean ± standard deviation), respectively. After a single administration of MDMA (10 mg/kg, i.p.), a dramatic increase in extracellular dopamine (C max : 36.1-fold vs. baseline) and 5-HT levels (C max : 9.3-fold vs. baseline) was observed. When rats were co-administered with methamphetamine (1, 5 or 10 mg/kg) with MDMA, the dopamine levels induced by MDMA increased in a methamphetamine-dose-dependent manner (C max : 2.5-, 3.5-, and 3.8-fold vs. MDMA). A similar trend was observed in 5-HT levels (C max : 1.1-, 1.3-, and 1.8-fold vs. MDMA). In contrast, ketamine and caffeine showed synergistic effects on the monoamine levels induced by MDMA, whereas the individual administration of either of these compounds did not affect monoamine levels. Ketamine (1, 5 mg/kg) decreased the dopamine levels induced by MDMA (C max : 0.9-and 0.7-fold vs. MDMA) and increased the 5-HT levels induced by MDMA (C max : 1.4-and 1.6-fold vs. MDMA), and co-administration of caffeine (20 2 mg/kg) with MDMA increased dopamine levels (C max : 1.7-fold vs. MDMA). These results suggest that exposure to multiple drugs in addition to MDMA can have neurotoxic effects. 249 words

Effect of ketamine administration, alone and in combination with E-6837, on climbing behavior

“…These findings coincide with a previous report of bidirectional effects on the level of anxiety recorded in mice that had been stressed and treated with distinct doses of buspirone, a partial 5-HT1A agonist (Briones-Aranda et al, 2002). This evidence indicates the importance of external factors in the regulation of specific behaviors as ketamine treatment (Ikeda et al, 2011) and stress (Briones et al, 2015) increase the concentration of brain DA and 5-HT, which in turn could influence the actions of nonselective serotonergic agents.…”

A Chemical Perspective of Pharmacology and Toxicology

“…These interactions result in a net increase of neurotransmitter release from the presynaptic terminal (DA or norepinephrine). Multiple brain studies using microdialysis methods and studies with transporter knockout mice have subsequently confirmed this event (see, for example, [41][42][43][44][45]. These analyses indicated micromolar concentrations of DA and 5-hydroxytryptamine (5-HT) can be achieved in extracellular space.…”

Evaluation of the neurochemical effects of methoxetamine using brain microdialysis in mice

“…Previously, we showed that i.p. methamphetamine (10 mg/kg) and 3,4-methylenedioxymethamphetamine (MDMA) (10 mg/ kg) increased dopamine concentration in the striatum of rats up to 6000 and 1620 % from baseline, respectively [14,15]. In addition, these drugs both increased serotonin concentrations in the striatum by up to 1300 %.…”

“…Forensic Toxicol HPLC-ECD conditions for determination of dopamine and serotonin HPLC-ECD conditions for determination of dopamine and serotonin concentrations were similar to those described in previous reports [14,15]. Briefly, the HPLC system was an HTEC-500 (Eicom) equipped with an ECD.…”

“…Therefore, it is important to evaluate effects of the abused drug on neurotransmitters in order to clarify the phenomena and/or influence caused by the drug. In the present study, this method was used to obtain samples from mouse brain, and dopamine and serotonin concentrations in the samples, as indicators of the effects caused by methoxetamine, were determined by high-performance liquid chromatography (HPLC) with electrochemical detection (ECD) using a method described in our previous reports [14,15].…”