Electrocortical effects of MDMA are potentiated by acoustic stimulation in rats (original) (raw)
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MDMA (ecstasy) modulates locomotor and prefrontal cortex sensory evoked activity
Brain Research, 2009
Ingestion of 3, 4-methylenedioxymethamphetamine (MDMA) leads to heightened response to sensory stimulation; thus, MDMA is referred to as "ecstasy" because it produces pleasurable enhancement of such sensation. There have been no electrophysiological studies that report the consequences of MDMA on sensory input. The present study was initiated to study the effects of acute and chronic MDMA on locomotor activity and sensory evoked field potential from freely behaving rats previously implanted with permanent electrodes in the prefrontal cortex (PFC). The main findings of this study are that: (1) acute MDMA augments locomotor behavior and attenuates the incoming sensory input, (2) chronic treatment of MDMA elicits behavioral sensitization, (3) chronic administration of MDMA results in attenuation of the baseline activity of the sensory evoked field potential, and (4) administration of rechallenge MDMA result in enhancement of the PFC sensory evoked field potential.
Brain Research Bulletin, 2008
a b s t r a c t MDMA (3,, also known as ecstasy, is a popular drug often taken in environments rich in audio and visual stimulation, such as clubs and dance parties. The present experiments were conducted to test the notion that auditory stimulation influences the rewarding effects of MDMA. In Experiment 1, a conditioned place preference (CPP) procedure was conducted in which rats received MDMA (1.5 mg/kg, s.c.) in a distinctive environment accompanied by music (65-75 dB), white noise (70 dB), or no added sound. Animals were pretreated with saline on alternating days in an alternate environment. Results revealed CPP in animals exposed to white noise during MDMA trials. For Experiment 2, rats from Experiment 1 had access to operant levers that delivered intravenous MDMA (0.5 mg/kg/inj) or saline (0.1 ml) on alternate days in the presence or absence of the same types of auditory stimuli as previously experienced. After three each of MDMA and non-reinforced (saline) sessions, animals were tested for NAcc DA and 5-HT responses to MDMA (1.5 mg/kg) or saline under the same stimulus conditions. Findings revealed that NAcc DA and 5-HT increased after an MDMA injection, and both DA and 5-HT were significantly highest in animals exposed to music during the test session. These results indicate that paired sensorial stimuli can engage the same systems activated during drug use and enhance neurochemical and behavioral responses to MDMA administration.
International Journal of Neuroscience, 2019
Background: This study was conducted to investigate the short-term behavioral and neurophysiological effects of MDMA (3,4-methylenedioxymethamphetamine) on tinnitus perception. Methods: A doubleblind randomized controlled cross-over design. Part 1. Behavioural measures of tinnitus following 30 mg MDMA or placebo administration (N=5 participants) and Part 2. Behavioral measures of tinnitus and correlations between pairs of apriori regions of interest (ROI) using resting-state functional magnetic resonance imaging (rs-fMRI) before and after 70 mg of MDMA or placebo (N=8 participants). Results: The results to MDMA were similar to placebo. For the 70 mg dose there was a significant reduction after 4 hours in annoyance and ignore ratings. RsMRI showed decreased connectivity compared to placebo administration between the left hippocampal, right hippocampal, left amygdala and right amygdala regions, and between the right posterior parahippocampal cortex and the left amygdala after two hours of 70 mg MDMA administration. Increased connectivity compared to placebo administration was found post MDMA between the right post-central gyrus and right posterior and superior temporal gyrus, and between the thalamus and frontoparietal network. Conclusions: Following 70 mg of MDMA two tinnitus rating scales significantly improved. There was, however, a placebo effect. Compared to placebo the rsMRI following the MDMA showed reductions in connectivity between the amygdala, hippocampus and parahippocampal gyrus. There is sufficient proof of concept to support future investigation of MDMA as a treatment for tinnitus.
Human Ecstasy Use is Associated with Increased Cortical Excitability: An fMRI Study
Neuropsychopharmacology, 2011
The serotonergic neurotoxin, 3,4-methylenedioxymethamphetamine (MDMA/Ecstasy), is a highly popular recreational drug. Human recreational MDMA users have neurocognitive and neuropsychiatric impairments, and human neuroimaging data are consistent with animal reports of serotonin neurotoxicity. However, functional neuroimaging studies have not found consistent effects of MDMA on brain neurophysiology in human users. Several lines of evidence suggest that studying MDMA effects in visual system might reveal the general cortical and subcortical neurophysiological consequences of MDMA use. We used 3 T functional magnetic resonance imaging during visual stimulation to compare visual system lateral geniculate nucleus (LGN) and Brodmann Area (BA) 17 and BA 18 activation in 20 long abstinent (479.95±580.65 days) MDMA users and 20 non-MDMA user controls. Lifetime quantity of MDMA use was strongly positively correlated with blood oxygenation level-dependent (BOLD) signal intensity in bilateral LGN (r s ¼ 0.59; p ¼ 0.007), BA 17 (r s ¼ 0.50; p ¼ 0.027), and BA 18 (r s ¼ 0.48; p ¼ 0.031), and with the spatial extent of activation in BA 17 (r s ¼ 0.059; p ¼ 0.007) and BA 18 (r s ¼ 0.55; p ¼ 0.013). There were no between-group differences in brain activation in any region, but the heaviest MDMA users showed a significantly greater spatial extent of activation than controls in BA 17 (p ¼ 0.031) and BA 18 (p ¼ 0.049). These results suggest that human recreational MDMA use may be associated with a long-lasting increase in cortical excitability, possibly through loss of serotonin input to cortical and subcortical regions. When considered in the context of previous results, cortical hyper-excitability may be a biomarker for MDMA-induced serotonin neurotoxicity.
…, 2002
Rationale: Decreased 5-HT function has been shown to induce behaviour consistent with an "anxiolytic" effect. Administration of a single dose of 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy" 12.5 mg/kg IP) to rats results in prolonged damage to central serotonergic nerve terminals. Thus we wished to assess whether an MDMA-induced lesion may have longer-term behavioural consequences. Objective: The study was designed to examine the behaviour of MDMA-pretreated and control animals in the elevated plus-maze and open field at a number of time-points, up to 80 days, after the administration of a single neurotoxic dose of MDMA (12.5 mg/kg IP). Results: MDMApretreated Dark Agouti rats demonstrated a statistically significant reduction in anxiety-related behaviour, compared to saline-pretreated control rats, in both the elevated plus-maze and open field when the rats were tested on day 73 (open field) and day 80 (plus maze) after MDMA administration. Conclusions: The behavioural consequences of a single neurotoxic dose of MDMA can be demonstrated over 2 months after administration of the compound, thereby indicating that long-term adaptive changes occur within the brain following the neurodegeneration of 5-HT neurones produced by this recreationally used drug.
Relevance of MDMA ("ecstasy")-induced neurotoxicity to long-lasting psychomotor stimulation in mice
Psychopharmacology, 2003
Although many studies have focused on the mechanisms underlying MDMA-induced neurotoxicity, little is known about the subsequent long-term response to psychostimulants following exposure to a neurotoxic dose of MDMA. We investigated the effect of pre-exposure to neurotoxic and non-neurotoxic doses of MDMA on the response of mice to the psychomotor stimulating effects of MDMA and cocaine. To investigate MDMA-induced neurotoxicity, male Swiss Webster mice were subjected to three regimens of MDMA: i) 40 mg/kg x 2, ii) 30 mg/kg x 2, and iii) 15 mg/kg x 2 for 2 days. On day 5 following the last exposure to MDMA, the levels of dopaminergic and serotonergic markers were determined. For the behavioral experiments, mice received either a single injection of 10 mg/kg MDMA [MDMA(L)] or one of the following doses of MDMA: 30 mg/kg x 2 or 15 mg/kg x 2 for 2 days [MDMA (H)]. A third group received saline as a control. On day 5 after the last pretreatment injection, the first MDMA (10 mg/kg) chall...
Imaging brain activity in conscious monkeys following oral MDMA (“ecstasy”)
Magnetic Resonance Imaging, 2006
Recreational use of 3,4-methylenedioxymethamphetamine (MDMA;becstasy Q) poses worldwide potential health problems. Clinical studies show that repeated exposure to low oral doses of MDMA has toxic effects on the brain, altering cognitive and psychosocial behavior. Functional magnetic resonance imaging in conscious marmoset monkeys was used to evaluate the sensitivity of the brain to an oral dose of MDMA (1 mg/kg). Following MDMA administration, the midbrain raphe nuclei and substantia nigra, major sources of serotonin and dopamine, were activated as were the hippocampus, hypothalamus and amygdala. The corticostriatal circuit of dorsal thalamus, sensorimotor cortex and basal ganglia showed a robust, coherent activation pattern. Two key reward areas, the nucleus accumbens and prefrontal cortex, and most other cortical regions showed little activation. The visual cortex, however, showed intense activation without applied visual stimuli. These data identify brain areas and functional circuits sensitive to a recreational dose of MDMA, some of which may be vulnerable to longterm intermittent exposure to this drug.
Forensic Toxicology
Purpose MDMA is a psychoactive drug that has been increasingly abused worldwide, due to its entactogenic properties. However, concerns on its safety exist, particularly regarding its effects on attentional skills and performance. Evidence from the literature shows contrasting effects of MDMA. It generally acts as a pshychomotor stimulant, thus improving arousal and psychomotor function. However, MDMA has been demonstrated to negatively influence other skills. Consequently, human activities that require alertness, and accurate and quick reflexes (i.e. driving, operations at the workplace, etc.) could be negatively affected. In the present study, the effect of MDMA (0.1-20 mg/kg, intraperitoneally) on sensorimotor and startle/ prepulse inhibition responses was evaluated in a controlled rodent experimental setting. Methods Sensorimotor studies, evaluation of visual, acoustic, and tactile responses, evaluation of spontaneous locomotion, startle and repulse inhibition analyses were performed in an experimental controlled rodent model (rats and mice), following the administration of MDMA (0.1-20 mg/kg) intraperitoneally. Results Our findings show that all the MDMA-treated animals had impaired sensorimotor and prepulse inhibition responses compared to the control subjects at the early (5, 30 and 60 min) testing time points while all the effects disappeared, respectively, 6, 16 and 24 h post-MDMA treatment. Conclusions Within the ongoing debate on the safety of recreational abuse of MDMA, our results reveal acute prominent changes in sensorimotor and attentional performance, sensor response to external stimuli, and locomotor activity due to a single administration of a dose of MDMA (corresponding to a dose producing in humans both 'desirable' entactogenic effects and physiological adverse effects).
Effects of Acoustic Stimulation on Rat Behavior after Withdrawal of Methamphetamine
The Showa University Journal of Medical Sciences, 1990
Looomotor activity was observed with and without acoustic buzzer stimulation after withdrawal of multiple methamphetamine (MAP) administration. Male Wistar rats were treated repeatedly with intermittent administration of MAP. Increments of MAP were injected every other day (2.5-10 mg/kg, three or two times per day), to induce reverse tolerance without inducing neurotoxicity. The response to acoustic buzzer stimulation was observed using an open field apparatus. MAP induced and maintained reverse tolerance of stereotyped behavior for at least 4 weeks after the last injection. In the saline control group, increased locomotor activity during acoustic stimulation and its suppression after acoustic stimulation were observed. In the MAP group, however, this response to acoustic stimulation was not seen for 4 weeks after withdrawal of the drug. These data suggest that behavioral hyporesponsiveness to acoustic stimulation was induced by repeated MAP treatment, and that this insensitivity to acoustic simulation is a characteristic behavioral change caused by long-term MAP administration.
Background 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a popular recreational drug that has been shown to damage brain serotonin neurons in high doses. However, effects of moderate MDMA use on serotonin neurons have not been studied, and sex differences and the long-term effects of MDMA use on serotonin neurons have not been identified. We investigated the effects of moderate and heavy MDMA use, sex differences, and long-term effects of MDMA use on serotonin neurons in different brain regions.