Journal of Neuroscience
May 1, 2001
Harry W. Broening, Laronda L. Morford, Sandra L. Inman-Wood et al.
141 citations
MDMA exposure during a period equivalent to the late human third trimester causes lasting learning and memory impairments in rats, while exposure during the early third trimester has little effect. Rats given MDMA on days 11–20 after birth showed dose-related difficulties in sequential learning and spatial learning and memory, but not in swimming or cued learning. Body weight temporarily dropped but recovered to 90–95% of controls. Brain chemical changes were small and did not explain the learning deficits. These findings suggest MDMA may pose a previously unrecognized risk to the developing brain.
Journal of Neuroscience
March 12, 2008
Stéphane Doly, Emmanuel Valjent, Vincent Setola et al.
140 citations
The club drug MDMA (ecstasy) primarily causes serotonin release by reversing the serotonin transporter. This study in mice shows that blocking or removing the 5-HT2B receptor completely stops MDMA-induced hyperactivity and serotonin release in key brain regions (nucleus accumbens and ventral tegmental area). The 5-HT2B receptor acts presynaptically to regulate MDMA-stimulated serotonin release, a previously unknown role. These findings suggest that 5-HT2B receptor antagonists could be promising treatments for MDMA abuse.
Journal of Neuroscience
June 3, 2009
Atheir I. Abbas, Prem N. Yadav, Wei-Dong Yao et al.
131 citations
The scaffolding protein PSD-95, known for organizing glutamate receptors at synapses, also critically regulates serotonin 5-HT2A and 5-HT2C receptors. In mice lacking PSD-95, these serotonin receptors show reduced expression, abnormal distribution in dendrites, and impaired signaling. Hallucinogen-induced behaviors and the effects of atypical antipsychotics that target these receptors are disrupted. PSD-95 is essential for normal serotonergic receptor function, expanding its role beyond glutamate signaling.
Journal of Neuroscience
January 16, 2013
Terrell Holloway, José L. Moreno, Adrienne Umali et al.
122 citations
Severe stress during pregnancy in mice alters the expression of two brain receptors linked to schizophrenia: serotonin 5-HT2A increases and metabotropic glutamate mGlu2 decreases in the frontal cortex. These changes correspond to behavioral differences in adult offspring, such as a heightened response to a hallucinogenic drug and reduced antipsychotic-like effects of a mGlu2/3 agonist. Cross-fostering ruled out maternal care as a cause, and similar effects appeared after prenatal immune activation. The findings support the idea that early neurodevelopmental disruptions contribute to schizophrenia risk.
Journal of Neuroscience
February 2, 2011
José L. Moreno, Mitsumasa Kurita, Terrell Holloway et al.
122 citations
Maternal infection with influenza virus in mice alters the expression of serotonin and glutamate receptors in the frontal cortex of adult offspring, leading to behavioral changes relevant to schizophrenia. The 5-HT 2A receptor is upregulated and the mGlu 2 receptor is downregulated. Offspring show increased head-twitch responses to hallucinogens and reduced antipsychotic-like effects of a glutamate agonist, along with altered signaling pathways. These findings suggest a biochemical link between prenatal viral infection and schizophrenia-related behaviors, potentially guiding new treatments.
Journal of Neuroscience
November 1, 2001
Nigel P. Pedersen, W.w. Blessing
120 citations
MDMA (Ecstasy) raises body temperature partly by constricting blood vessels near the skin's surface, which reduces the body's ability to release heat. In conscious rabbits, MDMA caused a dose-dependent increase in body temperature (from about 38.3 to 41.2 °C after 6 mg/kg) along with a sharp drop in ear pinna blood flow (from 29 to 5 cm/sec), indicating cutaneous vasoconstriction. Blocking sympathetic nerves on one side of the head reduced both the temperature rise and the vasoconstriction. This suggests that sympathetically mediated skin vessel narrowing is a key mechanism behind MDMA-induced hyperthermia, and reversing that constriction might help treat life-threatening overheating in humans.
Journal of Neuroscience
December 15, 2001
Evelyn K. Lambe, George K. Aghajanian
111 citations
Blocking potassium channels that contain the Kv1.2 subunit triggers glutamate release in the rat prefrontal cortex, mimicking the effect of serotonin on thalamocortical terminals. The potassium channel blocker α-dendrotoxin (DTX), which selectively targets Kv1.1-, Kv1.2-, and Kv1.6-containing channels, induced excitatory postsynaptic currents (EPSCs) in layer V pyramidal neurons similar to those caused by serotonin acting on 5-HT2A receptors. Both DTX- and serotonin-induced EPSCs were blocked by tetrodotoxin and ω-agatoxin-IVA, suppressed by μ-opiates and thalamic lesions, and showed mutual occlusion, indicating a shared mechanism. This suggests that serotonin triggers glutamate release by inhibiting Kv1.2-containing potassium channels on thalamocortical terminals.
Journal of Neuroscience
October 8, 2003
Mahmoud M. Iravani, Michael S. Jackson, Mikko Kuoppamäki et al.
105 citations
MDMA (ecstasy) reduced dyskinesia and extended the effect of L-DOPA in a single Parkinson's disease patient. In MPTP-treated marmosets primed with L-DOPA, MDMA given alone transiently relieved motor disability but worsened symptoms over 60 minutes. When combined with L-DOPA, MDMA markedly decreased dyskinesia by reducing chorea and, to a lesser extent, dystonia, and lowered locomotor activity to normal levels. MDMA also alleviated dyskinesia induced by the dopamine D2/3 agonist pramipexole. These effects were fully blocked by the serotonin reuptake inhibitor fluvoxamine and partially inhibited by 5-HT1a/b antagonists, indicating MDMA's antidyskinetic action is mediated through serotonin systems.
Journal of Neuroscience
November 23, 2011
Benjamin Di Cara, Roberto Maggio, Gabriella Aloisi et al.
97 citations
MDMA (ecstasy) activates trace amine-1 receptors (TA1Rs), which normally inhibit dopamine and serotonin release. In mice lacking TA1Rs, MDMA caused only hyperthermia (not the biphasic temperature response seen in normal mice), produced larger increases in dopamine levels in the striatum, frontal cortex, and nucleus accumbens, and led to greater locomotion that was blocked by haloperidol. Serotonin release was also amplified in TA1R-deficient mice. A TA1R agonist reduced the dopamine- and serotonin-releasing effects of another drug in normal mice but not in knockout mice. TA1Rs thus limit MDMA's neurochemical and behavioral effects, suggesting they play a regulatory role in the drug's actions.
Journal of Neuroscience
January 21, 2015
Elisa Filevich, Martin Dresler, Timothy R. Brick et al.
89 citations
People who frequently have lucid dreams—dreams in which they know they are dreaming—show structural and functional differences in a brain region linked to self-reflection and thought monitoring. The frontopolar cortex (BA9/10) contained more gray matter in high-lucidity dreamers compared with low-lucidity dreamers, and this same area showed stronger activity during a thought-monitoring task in the high-lucidity group. The findings suggest that lucid dreaming and metacognitive abilities share common neural systems, offering insight into how higher-order consciousness can arise during sleep.
Journal of Neuroscience
May 11, 2011
Philippe Huot, Tom H. Johnston, Katie D. Lewis et al.
83 citations
The drug MDMA, composed of two mirror-image forms (enantiomers), shows promise for treating Parkinson's disease motor complications. R-MDMA reduced peak-dose dyskinesia severity by 33% at 3 mg/kg and 46% at 10 mg/kg, and cut the duration of disabling dyskinesia by 69% (90 minutes) without changing total ON-time. S-MDMA at 1 mg/kg extended total ON-time by 34% (88 minutes) but worsened dyskinesia. The findings suggest that racemic MDMA's simultaneous antidyskinetic and ON-time-extending effects arise from R-MDMA's action on 5-HT2A receptors and S-MDMA's inhibition of serotonin and dopamine transporters.
Journal of Neuroscience
March 19, 2018
Katrin H. Preller, Leonhard Schilbach, Thomas Pokorny et al.
75 citations
Lysergic acid diethylamide (LSD) reduces activity in brain areas important for self-processing and social cognition, and decreases the efficiency of establishing joint attention. These effects are attributable to stimulation of the serotonin 2A receptor (5-HT2AR), as they are blocked by the antagonist ketanserin. The findings point toward the 5-HT2AR system as a potential target for treating social impairments in psychiatric disorders.
Journal of Neuroscience
June 4, 2014
Eugene A. Kiyatkin, A. H. Kim, Ken T. Wakabayashi et al.
47 citations
MDMA (Ecstasy) can cause fatal brain hyperthermia when taken in hot, crowded environments, even at moderate doses that are harmless under cool, quiet conditions. In male rats, MDMA at 9 mg/kg (about one-fifth of the lethal dose) produced only weak brain temperature increases under standard lab conditions (quiet rest, 22–23°C). However, social interaction with another male rat and a warm environment (29°C) dramatically amplified brain hyperthermia. The key mechanism is peripheral vasoconstriction, which prevents heat dissipation through the skin. This shows that doses of MDMA that are nontoxic in cool, quiet settings become highly dangerous under conditions mimicking recreational use at rave parties or other hot, crowded venues.
Journal of Neuroscience
November 19, 2018
Anthony S. Gabay, Matthew J. Kempton, James Gilleen et al.
40 citations
MDMA increases cooperative behavior, but only when interacting with trustworthy partners. In a double-blind, placebo-controlled crossover study, 20 male participants received 100 mg MDMA or placebo and played an iterated Prisoner's Dilemma with opponents who varied in cooperation. MDMA enhanced cooperation with trustworthy opponents (odds ratio = 2.01) but not untrustworthy ones. MDMA specifically improved recovery from, not the impact of, breaches in cooperation. Brain activity increased in regions linked to social cognition, including precentral and supramarginal gyri, superior temporal cortex, central operculum/posterior insula, and supplementary motor area. Trust ratings did not change. The effect of MDMA on social decision-making depends on the context of the other person's behavior.
Journal of Neuroscience
March 4, 2020
S. Maillé, M. Lynn
21 citations
The neural basis of consciousness remains a fundamental challenge in modern neuroscience. Several sophisticated models and theories attempt to formalize how the brain implements consciousness, drawing on insights from philosophy, psychology, computer science, and neuroscience.
Journal of Neuroscience
December 19, 2025
Nicolas G. Glynos, Emma R. Huels, Trent Groenhout et al.
In rats, intravenous DMT causes dose-dependent increases in serotonin and dopamine in the medial prefrontal and somatosensory cortices, along with distinct changes in brain wave patterns: reduced theta and low gamma power, increased delta, medium gamma, and high gamma power, and altered functional connectivity. Head twitch responses were most frequent at the lowest dose. Endogenous DMT was detected in the cortex of most animals at baseline, suggesting it may be naturally present. The work provides a detailed neurochemical and neurophysiological profile of DMT action in rats.
Journal of Neuroscience
November 10, 2025
Sarah N. Magee, Allison C. Sereno, Maria Echeveste-Sanchez et al.
Psilocin, the active metabolite of psilocybin, acutely reduced voluntary ethanol consumption in mice exposed to two models of chronic ethanol exposure without altering locomotor behavior. It increased activation of the central amygdala (CeA) and decreased relative activation of corticotropin-releasing factor type 1 (CRF1) receptors in CeA subregions of ethanol-naive female mice, with similar effects observed in chronic ethanol-exposed mice at 24 and 72 hours of withdrawal. Psilocin also elevated corticosterone levels at 24 hours but not at 72 hours of withdrawal. These findings indicate that psilocin engages CeA circuitry and reduces relative CRF1 activation alongside acute reductions in drinking, helping explain potential therapeutic mechanisms for alcohol use disorder.