Brain research
November 21, 1983
P H Hutson, M D Tricklebank, G Curzon
13 citations
Analgesia caused by a brief footshock in rats is reduced by drugs that increase serotonin (5-HT) activity—fenfluramine, which releases serotonin, and 5-MeODMT, a fast-acting serotonin agonist. These reductions are blocked by serotonin antagonists cyproheptadine and methiothepin, but those antagonists alone do not affect the shock-induced pain relief. Thus, the natural analgesia from brief footshock likely does not rely on serotonin mechanisms, though it can be altered by pharmacologically boosting serotonin. 5-MeODMT could also weaken analgesia after it starts, possibly by disrupting memory rather than pain processing directly.
Brain research
August 8, 1983
M Simonovic, H Y Meltzer
12 citations
5-MeODMT, a serotonin receptor agonist, has a two-phase effect on prolactin secretion in rats. It initially causes a short, dose-dependent increase in serum prolactin levels, lasting less than 30 minutes. After 30 minutes, it inhibits prolactin release stimulated by other serotonin agonists, alpha-methylparatyrosine, or low-dose haloperidol, but does not alter the effect of gamma-butyrolactone or high-dose haloperidol. The initial rise likely results from activating postsynaptic serotonin receptors, while the later inhibition appears due to increased activity of dopamine neurons. This biphasic pattern is also seen with quipazine but not with 5-MeOT, which does not cross the blood-brain barrier.
Brain research
November 13, 1999
M E Alburges, G R Hanson
11 citations
Ibogaine, a psychoactive alkaloid from the shrub Tabernanthe iboga used to treat stimulant addiction, does not by itself alter dynorphin levels in key brain regions such as the striatum, substantia nigra, or nucleus accumbens. However, when given before cocaine, ibogaine dramatically amplifies cocaine-induced increases in dynorphin content in those same structures. This suggests ibogaine may influence addiction-related brain pathways by modulating dynorphin responses to cocaine, offering insights into its anti-addiction potential.
Brain research
October 17, 1997
Hemendra N Bhargava, Ying-Jun Cao
10 citations
Noribogaine, a metabolite of ibogaine, reduced the development of tolerance to morphine's pain-relieving effect in male Swiss-Webster mice. Tolerance was induced by implanting a 25 mg morphine pellet for 4 days or by injecting morphine (20 mg/kg) twice daily for 4 days. In pellet-implanted mice, 20 mg/kg of noribogaine attenuated tolerance, while lower doses had no effect. In mice receiving multiple injections, 20 and 40 mg/kg doses also attenuated tolerance. Since noribogaine worked at lower doses than ibogaine (which required 40–80 mg/kg in previous work), the authors suggest ibogaine's effect may depend on its conversion to the more active noribogaine.
Brain research
November 15, 2024
Lijuan Wang, Shuwu Zhao, Jiali Shao et al.
7 citations
In a rat model of neuropathic pain caused by nerve injury, low-dose esketamine relieved depression-like behaviors such as reduced mobility in a forced swim test and decreased preference for sucrose. The drug did not significantly change pain sensitivity. Proteomic analysis of the medial prefrontal cortex revealed that esketamine reversed the upregulation of mGluR5 and Homer1a proteins seen in the pain-depression model. The Homer1a–mGluR5 signaling pathway may underlie esketamine's antidepressant effect in neuropathic pain-related depression.
Brain research
August 26, 1996
R A Rabin, J C Winter
7 citations
The antiaddictive compound ibogaine and its primary metabolite noribogaine were tested for their effects on phosphoinositide hydrolysis in rat brain tissue. Ibogaine did not alter phosphoinositide turnover in striatal or hippocampal slices, but noribogaine caused a concentration-dependent increase in the generation of inositol phosphates. This increase was not due to neurotransmitter release, as it was unaffected by tetrodotoxin, cadmium, or omega-conotoxin. The results suggest that noribogaine's stimulation of phosphoinositide hydrolysis may contribute to the behavioral effects of ibogaine.
Brain research
January 15, 2025
Lijie Zhou, Xianlei Wang, Tianyu Cao et al.
4 citations
Repeated high-dose esketamine exposure in infant male rats leads to long-term behavioral deficits and changes in white matter microstructure. Seven-day-old rats given high doses showed reduced activity, impaired short-term memory, longer immobility in forced swimming, and motor coordination problems compared to controls. Diffusion tensor imaging revealed decreased water diffusion in the corpus callosum, and tissue staining showed microstructural white matter changes. These findings suggest that behavioral impairments from high-dose esketamine are at least partially due to alterations in white matter.
Brain research
January 1, 2025
Ernestas Cizus, Urte Jasinskyte, Robertas Guzulaitis
3 citations
Acute suppression of NMDA receptors in mice alters brain oscillations across a wide frequency spectrum and diminishes oscillatory potency in evoked responses, paralleling changes seen in schizophrenia. Chronic suppression of NMDA receptors did not produce the expected cumulative effect on brain activity. The findings highlight robust yet similar impacts of acute and chronic NMDA receptor suppression on brain oscillations, contributing to a nuanced understanding of rodent models of schizophrenia.
Brain research
March 1, 2025
Jannik Nicklas Eliasen, Uffe Kristiansen, Kristi A Kohlmeier
2 citations
Psychedelics like DMT and ibogaine activate the 5-HT2A receptor, a G protein-coupled receptor, to produce therapeutic effects. Naturally occurring genetic variations (SNPs) in this receptor alter its function and drug responsiveness. Using whole-cell electrophysiology on HEK cells expressing either the normal or a mutated (I197V) human 5-HT2AR, membrane currents were observed in both genotypes with both drugs, but not in cells lacking the receptor, confirming the responses depend on 5-HT2AR activation. The I197V mutation shortened the DMT response duration without affecting amplitude. These findings demonstrate that 5-HT2AR-transfected HEK cells can be used to test novel compounds and evaluate SNP effects on drug-induced ion currents.
Brain research
February 11, 1985
R Lalonde, M I Botez
1 citation
Long-term administration of phenytoin (PHT) to male rats for 20 consecutive days reduced the intensity of a stereotyped motor response induced by the serotonin agonist 5-MDMT at 3 mg/kg when tested on day 21, but this effect was absent by day 28. A single injection of PHT did not alter the motor response. The authors suggest that PHT increases the functional availability of serotonin before its receptors, leading to serotonin receptor subsensitivity.
Brain research
June 19, 2025
Zoé Dary, Paul Kobliska, Jacques Léonard et al.
The vestibular system, which governs balance and spatial orientation, contributes to body and self perception, but its role in the immediate, pre-reflective sense of self (the bodily self) is not well understood. This study used a full-body illusion in virtual reality to examine how bilateral vestibulopathy (BVP), a disorder impairing vestibular function, affects the bodily self. Comparing 34 patients with partial or complete BVP, 34 age-matched healthy controls, and 34 younger controls, the results showed that BVP did not significantly alter the bodily self as measured. However, patients with total vestibular loss exhibited a larger drift in illusory self-location, suggesting otolithic signals are important for this aspect.