Journal of Neurochemistry
November 3, 2021
Aurora Savino, Charles D. Nichols
18 citations
Psychedelic drugs, including LSD, are being studied as potential treatments for psychiatric disorders like mood and substance use disorders. The 5-HT2A receptor is their main molecular target, and early research indicated effects on neuroplasticity genes. By analyzing RNA-sequencing data from the prefrontal cortex of rats chronically treated with LSD, the authors describe how psychedelics rewire gene co-expression networks, making them less centralized but more complex, with an overall increase in signaling entropy characteristic of highly plastic systems. This molecular-level signaling entropy mirrors the increased brain entropy observed in human neuroimaging studies, suggesting underlying mechanisms for higher-order phenomena. Network topology analysis identified potential transcriptional regulators and implicated different cell types in psychedelic activity.
Journal of Neurochemistry
August 1, 1989
I Hide, T Kato, S Yamawaki
15 citations
In the intact rat brain, phosphoinositide turnover is stimulated by activation of the 5-HT2 receptor. After prelabeling brain phosphoinositides with [3H]inositol, lithium treatment increased levels of [3H]IP1 and [3H]IP2. The 5-HT agonists 5-MeODMT and quipazine further increased 3H-inositol phosphate levels under lithium pretreatment. This response was blocked by the 5-HT2 antagonist ritanserin but not by the 5-HT1 antagonist (-)-propranolol, indicating that 5-HT2 receptors drive this signaling. The method can be used to study in vivo effects of psychotropic drugs like antidepressants on 5-HT2 receptor-stimulated phosphoinositide turnover.
Journal of Neurochemistry
September 1, 2024
Ana Sofia Alberto-Silva, Selina Hemmer, Hailey A. Bock et al.
10 citations
Three new chemical variants of MDMA—ODMA, TDMA, and SeDMA—show similar activity at serotonin, dopamine, and norepinephrine transporters but reduced activity at 5-HT2A/2B/2C receptors compared to MDMA. They also differ in liver metabolism, with N-demethylation as the only shared route and no phase II metabolites formed. TDMA showed faster clearance. The analogs interacted more weakly with organic cation transporters and plasma membrane monoamine transporter. These bioisosteres may offer therapeutic alternatives to MDMA with a reduced off-target profile, but further studies are needed to determine if they pose lower risks.
Journal of Neurochemistry
February 28, 2025
Aneta Petrušková, Debarpan Guhathakurta, Enes Yağız Akdaş et al.
8 citations
Serotonergic psychedelics like psilocybin, LSD, and DMT rapidly alter how neurons communicate at synapses. Using live-cell imaging in rat cortical neurons, the drugs reduced the fraction of synaptic vesicles that fuse in response to electrical stimulation within minutes, an effect that faded within 24 hours. DMT only reduced the total recycling pool of vesicles, while LSD and psilocin also shrank the readily releasable pool. Psilocin and DMT increased evoked glutamate release, yet LSD and psilocin lowered presynaptic calcium levels. Psilocin further depressed responses to paired stimuli. These drug-specific modulations of glutamatergic transmission may help explain their distinct therapeutic properties.
Journal of Neurochemistry
September 1, 2024
Risako Fujikawa, Jun Yamada, Shoichiro Maeda et al.
6 citations
In a mouse model of schizophrenia, the antipsychotic risperidone reduced behavioral abnormalities and altered microglial activity and reactive oxygen species (ROS) in the hippocampus. Mice given ketamine showed schizophrenia-like behaviors, increased microglial density, and a shift toward more activated microglial shapes. Risperidone reversed these changes, lowering expression of the ROS-producing enzyme Nox2 and raising antioxidant enzyme levels. In isolated microglia, ketamine boosted ROS production, which risperidone blocked. A NOX2 inhibitor also counteracted ketamine-induced behavioral deficits, suggesting that reducing ROS via microglial modulation may help treat schizophrenia.
Journal of Neurochemistry
November 1, 1966
G Badiu, N Mison-Crighel
4 citations
Topical application of mescaline to the neocortex induced an epileptiform spiking focus and altered nitrogenous compounds across the entire cerebral cortex. Within two minutes, before spiking began, ammonia levels rose significantly in all neocortical areas, especially at the focus and the homolateral marginal gyrus; free amide nitrogen decreased and non-protein nitrogen increased throughout the cortex. At thirty minutes, during focus development, ammonia remained elevated with a slight decline, free amide nitrogen was reduced in all neocortical areas, and protein nitrogen decreased in both marginal gyri while lipid nitrogen fell in the focus and both marginal gyri.
Journal of Neurochemistry
May 1, 2026
Jannik Nicklas Eliasen, Amir Rezagholizadeh, Helene Påbøl Jacobsen et al.
Dimethyltryptamine (DMT), a classic psychedelic with potential anti-depressive and anti-addictive properties, alters the electrical activity of certain neurons in the ventral tegmental area (VTA) of the mouse brain, with effects differing by sex. In an ex vivo study on I_h-negative neurons, a low concentration (500 nM) of DMT had no effect on electrophysiological properties in either sex. A high concentration (90 μM) increased action potential firing and changed membrane conductance at subthreshold potentials, but only in female neurons. DMT also raised cytosolic calcium levels in both sexes at the high concentration. The findings suggest that DMT activates mechanisms in females beyond the calcium changes seen in males, highlighting the importance of sex and dose in understanding its therapeutic potential.
Journal of Neurochemistry
January 29, 2026
Paola Andrea Caro Aponte, Edison Huertas Montoya, Ítalo Odone Mazali et al.
A combinatorial therapy combining surgical root reimplantation, a fibrin sealant biopolymer, and a low dose of dimethyltryptamine (DMT) extracted from Mimosa tenuiflora roots rescued motor neurons and reduced glial reactivity in a rat model of ventral root avulsion. Proximal axotomy caused 78% motor neuron loss, glial reactivity, and synaptic detachment. Daily DMT at 1 mg/kg for two weeks significantly increased motor neuron survival, reduced glial reactivity, and preserved pre-synaptic boutons. Combining DMT with surgical reimplantation further potentiated these effects and upregulated GDNF expression, suggesting a synergistic neuroprotective benefit. DMT shows promise as a neuroprotective agent for CNS/PNS interface injuries.
Journal of Neurochemistry
February 7, 2024
Kelly E. Dunham, Kani H. Khaled, Leah Weizman et al.
Ketamine, when given at very low (micro) doses, increases movement and feeding in fruit fly larvae, but through a different mechanism than standard antidepressants such as SSRIs. At 1 mM, ketamine did not alter serotonin levels yet still boosted locomotion and feeding, whereas low doses of the SSRIs escitalopram and fluoxetine inhibited the serotonin transporter (dSERT) and similarly increased these behaviors. At a high dose (100 mM), ketamine blocked dSERT and raised serotonin, but reduced movement and feeding due to anesthetic effects. Experiments with mutant flies and other drugs suggest ketamine's behavioral effects come from NMDA receptor antagonism (which increases feeding) and serotonin receptor activation (which increases locomotion), not from acting on the serotonin transporter like SSRIs.