Journal of neurochemistry
July 1, 2022
Hannah N Saeger, David E Olson
59 citations
Psychedelics show promise for treating depression, PTSD, and substance use disorder, potentially by reversing cortical atrophy through effects on neurotrophic factors, neuronal growth, and immune modulation. This review argues that similar approaches could benefit neurodegenerative disorders like Alzheimer's disease, where the primary psychedelic target, the 5-HT2A receptor, is dysregulated. Evidence also suggests psychedelics might help manage behavioral and psychological symptoms of dementia (BPSD). The authors call for more research in neurodegenerative models, emphasizing that the compounds' robust effects on neuroplasticity and inflammation warrant further investigation.
Journal of neurochemistry
December 1, 1996
R A Newton, S L Phipps, T P Flanigan et al.
46 citations
Cell lines engineered to express human 5-HT2A or 5-HT2C receptors showed ligand binding similar to natural receptors in brain tissue. Serotonin triggered stronger but less effective phosphoinositide signaling at 5-HT2C than at 5-HT2A receptors, and 5-HT2A activation briefly raised intracellular calcium fourfold. Both receptors produced a tiny inward current when stimulated. Among hallucinogens (LSD, DOI, DMT, mescaline) and nonhallucinogens, no differences in phosphoinositide signaling potency or efficacy emerged. LSD and DOI preferentially activated 5-HT2A, while m-CPP activated 5-HT2C. The findings suggest hallucinosis is not primarily mediated by 5-HT2C activity; 5-HT2A activation may be important but not the sole mechanism.
Journal of neurochemistry
January 1, 1986
J J Grome, A M Harper
40 citations
Rats given different types of serotonin-like drugs showed mostly reduced brain glucose use, but piperazine-based drugs increased glucose use in specific brain regions while indoleamine-based drugs did not. This suggests the two drug types produce both similar and different patterns of brain activity.
Journal of neurochemistry
September 1, 1985
U Spampinato, E Esposito, R Samanin
36 citations
In rats, two serotonin agonists, 5-MeO-DMT and CPP, did not reduce dopamine synthesis in the striatum when impulse flow in dopamine neurons was blocked by gamma-butyrolactone, unlike the dopamine agonist apomorphine. However, when impulse flow was intact, both serotonin agonists did reduce dopamine synthesis. Injecting serotonin directly into the substantia nigra increased dopamine synthesis, similar to blocking impulse flow. The findings suggest that serotonin agonists affect dopamine synthesis indirectly, possibly through other neurons like cholinergic or GABA-ergic ones, and only when dopamine neurons are active.
Journal of neurochemistry
April 1, 2019
Ali Y Benkherouf, Kaisa-Riitta Taina, Pratap Meera et al.
26 citations
Muscimol, the psychoactive compound from the Amanita muscaria mushroom, binds with high affinity to a specific subtype of GABAA receptors that contain the δ subunit. Deleting the δ subunit in mice eliminates more than 50% of high-affinity muscimol binding sites in the brain, even though δ-containing receptors are relatively scarce. Native δ-GABAA receptors in wild-type mice show binding affinities around 1–2 nM, and incorporating the δ subunit into recombinant receptors produces currents with slow deactivation and extreme sensitivity to muscimol. The findings indicate that δ subunit incorporation dramatically increases muscimol sensitivity, explaining low-dose selectivity for δ-containing receptors in biochemical and behavioral experiments.
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
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.