Neuroscience letters
June 2, 1995
D C Mash, J K Staley, J P Pablo et al.
82 citations
Ibogaine and its metabolite 12-hydroxyibogamine act at the MK-801 binding site within the NMDA-receptor cation channel. Both compounds competitively displaced [3H]MK-801 binding to membranes from human caudate, cerebellum, and frog spinal cord. Ibogaine was 4-6 times more potent than its metabolite, but both were 50-1000 times less potent than MK-801. Ibogaine (100 µM) and 12-hydroxyibogamine (1 mM) blocked NMDA-induced depolarizations in frog motoneurons by 85-90%. The block was use-dependent and resembled that of MK-801. These findings suggest that ibogaine's ability to interrupt drug-seeking behavior may partly result from its action at the MK-801 binding site.
Neuroscience letters
September 25, 2022
Alaina M Jaster, Jason Younkin, Travis Cuddy et al.
53 citations
The psychedelic compound DOI triggers more head-twitch behavior—a mouse proxy for human psychedelic effects—in female C57BL/6J mice than in males, a sex difference not seen in 129S6/SvEv mice. The 5-HT2A receptor antagonist volinanserin fully blocked this behavior in both sexes. Despite greater behavioral sensitivity in females, brain and plasma levels of DOI were lower in females 30 and 60 minutes after injection, and no sex difference appeared in frontal-cortex IP1 accumulation. These findings indicate strain-dependent and sex-related differences in the behavioral and pharmacokinetic responses to DOI, underscoring the need to include sex as a biological variable in preclinical psychedelic research.
Neuroscience letters
September 1, 1980
O G Berge, K Hole, H Dahle
34 citations
Injecting 5-methoxy-N,N-dimethyltryptamine into the brain's ventricles altered pain sensitivity in rats, measured by the tail-flick test. Low doses (1.6 to 25 micrograms) reduced tail-flick latencies by 13-24%, indicating hyperalgesia (increased pain sensitivity), likely from decreased activity in descending serotonergic neurons. Moderate doses (50 and 100 micrograms) produced a biphasic response: initial hyperalgesia followed by analgesia. The highest dose (400 micrograms) increased latencies by 28-39%, indicating analgesia, probably by stimulating spinal postsynaptic serotonergic receptors.
Neuroscience letters
May 19, 1987
T Nabeshima, K Ishikawa, K Yamaguchi et al.
27 citations
Phencyclidine (PCP) causes a head-twitch response in mice and rats that is completely blocked by ritanserin, a serotonin 5-HT2 receptor antagonist, indicating the involvement of 5-HT2 receptors. The same antagonism occurs for head-twitch induced by 5-MeODMT in mice. After ritanserin treatment, PCP and 5-MeODMT still produce head-weaving in mice but not in rats. In rats, 5-MeODMT does not cause head-twitch. These results suggest that PCP-induced head-twitch in rats is mediated by 5-HT2 receptors, making it a useful model for studying those receptors, while 5-MeODMT-induced head-weaving in rats involves 5-HT1 receptors.
Neuroscience letters
December 23, 1982
T Archer, S O Ogren, S B Ross
24 citations
Drugs that increase serotonin activity—5-MeO-DMT, fenfluramine, and PCA—impair rats' ability to retain fear, as shown by reduced immobility after inescapable shocks. Long-term PCA treatment, which depletes central serotonin neurons, completely blocked the retention impairment caused by acute PCA and fenfluramine, and partially blocked the deficit from 5-MeO-DMT. However, serotonin depletion via PCPA did not block these effects, suggesting different serotonin stores are involved. These findings underscore the role of the ascending serotonin pathway in aversive conditioning in rats.
Neuroscience letters
April 13, 1992
Y Wada, H Hasegawa, M Nakamura et al.
21 citations
A serotonin receptor agonist, 5-MeODMT, suppresses light-triggered muscle jerks but not abnormal EEG activity in kindled cats. At a dose of 4 mg/kg, the drug reduced photically induced myoclonus for 30 to 60 minutes after injection, accompanied by behavioral signs resembling serotonin syndrome. The findings indicate that serotonin, acting through 5-HT1 receptors, plays a key role in photosensitive epilepsy.
Neuroscience letters
May 14, 2024
Daniele Cavaleri, Ilaria Riboldi, Cristina Crocamo et al.
13 citations
Ketamine and esketamine are known to relieve depression, but how they work at the molecular level remains unclear. This mini-review summarizes studies using metabolomics to examine metabolic changes after low-dose ketamine or esketamine in animals and humans. Both types of studies show alterations in pathways related to energy production (tricarboxylic acid cycle, glycolysis, pentose phosphate pathway), lipid and amino acid metabolism, the kynurenine pathway, and the urea cycle. These findings suggest the drugs influence mitochondrial function, energy metabolism, membrane maintenance, and cell signaling. Metabolomics may help uncover markers of treatment response and guide personalized depression care, though more research is needed to distinguish effects of the racemic drug from its enantiomers.
Neuroscience letters
August 14, 1989
B A Heidenreich, G V Rebec
13 citations
In rats pretreated with a high dose of D-amphetamine for six days, serotonergic neurons in the dorsal raphe nucleus showed a trend toward increased spontaneous firing rate and reduced responsiveness to the autoreceptor agonist 5-MeODMT compared to controls. The most notable effect was a strong correlation between spontaneous activity and drug response: faster-firing cells required higher doses of 5-MeODMT to be inhibited. No such correlation appeared in control animals. These results suggest that repeated amphetamine administration alters serotonergic autoreceptor sensitivity in the dorsal raphe.
Neuroscience letters
July 19, 1988
P K Eide, K Hole
11 citations
Injecting substance P into the spinal cord of mice temporarily caused a behavioral syndrome but no lasting toxic effects or changes in pain sensitivity measured by tail-flick response to heat. However, when given 30 minutes later, the pain-suppressing effect of the serotonin receptor agonist 5-MeODMT was markedly reduced. Skin temperatures were nearly identical between substance P and control groups, ruling out temperature changes as a confound. These results indicate a functional interaction between substance P and serotonin in spinal pain processing, suggesting that intrathecal substance P modulates serotonin receptor function.
Neuroscience letters
June 21, 2024
Carlos M Contreras, Ana G Gutiérrez-García
4 citations
Ketamine, a dissociative anesthetic proposed for treatment-resistant depression, produces beneficial clinical effects only after its psychotropic actions fade, suggesting dose-independent mechanisms. This study compared an anesthetic dose of ketamine with a high dose of fluoxetine in Wistar rats 24 hours after administration. Fluoxetine reduced immobility in the forced swim test without affecting locomotor activity, while ketamine strongly decreased locomotor activity and did not change immobility. In separate rats, lateral septal nucleus (LSN) stimulation produced a long-lasting inhibitory afterdischarge in prelimbic and infralimbic cortices. Both ketamine and fluoxetine accentuated this inhibition, indicating that despite different neurotransmission actions, antidepressants may share a common final pathway involving forebrain structures linked to emotional regulation.
Neuroscience letters
December 13, 1982
A A Larson
4 citations
Injecting 100 micrograms of 5-MeODMT into the spinal subarachnoid space of conscious rats reduced nociceptive reflex reaction times, indicating a hyperalgesic effect. Administration into the thoracic region decreased the average percent of control reaction time by 14%, while injection into the lumbosacral region produced a 25% decrease. This facilitatory effect on pain perception mimics tryptamine rather than serotonin, suggesting 5-MeODMT interacts with tryptaminergic receptors in the spinal cord.
Neuroscience letters
August 10, 2024
Isis M Ornelas, Beatriz de S Carrilho, Matheus Antonio V de C Ventura et al.
3 citations
Lysergic acid diethylamide (LSD), a synthetic psychedelic compound with potential therapeutic value for psychiatric disorders, is absorbed by the nematode Caenorhabditis elegans and acutely reduces its speed, an effect similar to that of endogenous serotonin. This response is partially mediated by the serotonergic receptors SER-1 and SER-4. The findings highlight the potential of C. elegans as a new experimental model for psychedelic research.
Neuroscience letters
June 21, 2024
Barbara G Ferri, Cintia O De Novais, Viviana C T Rojas et al.
3 citations
In a rat model of sepsis-associated encephalopathy, the psychedelic phenethylamine 25H-NBOMe reduced depressive-like behaviors and signs of neuroinflammation. Rats that underwent cecal ligation and puncture surgery to induce sepsis showed decreased immobility and increased swimming times in the forced swim test after treatment, indicating fewer depressive symptoms. The compound also increased head-twitch responses, confirming its psychoactive effects, and lowered GFAP expression in the prefrontal cortex, suggesting reduced astrogliosis. The findings indicate that 25H-NBOMe can alleviate post-sepsis depression and neuroinflammation, but its psychedelic properties warrant investigation of similar compounds with fewer psychoactive effects.
Neuroscience letters
June 21, 2024
Yingbing Tu, Bin Xu
3 citations
Esketamine improved spatial learning and memory in triple transgenic Alzheimer's disease (3xTg-AD) mice. The drug increased expression of TRIM24, which activated the PI3K/AKT pathway in the hippocampus. Depleting TRIM24 reversed these cognitive benefits and blocked PI3K/AKT signaling. Esketamine also reduced neuroinflammation—lowering pro-inflammatory molecules, GFAP, and p-Tau—but this effect was lost when TRIM24 was knocked down. Blocking the PI3K/AKT pathway worsened cognitive deficits and inflammation. Thus, esketamine may counteract Alzheimer's-related cognitive decline by suppressing neuroinflammation through the TRIM24/PI3K/AKT axis.
Neuroscience letters
November 20, 2024
Angeliki Metaxia Styla, Nikolaos Pitsikas
2 citations
A combination of low, individually inactive doses of donepezil (0.3 mg/kg) and ketamine (1 mg/kg) given after training prevented impairments in both non-spatial and spatial recognition memory in rats. The findings, though preliminary, suggest that pairing these two drugs might offer a new approach for treating memory problems common in Alzheimer's disease.
Neuroscience letters
January 18, 2024
Hector Vargas-Perez, Fernando Minauro-Sanmiguel, Ryan Ting-A-Kee et al.
2 citations
A classic theory of addiction, opponent-process theory, holds that a drug's immediate rewarding effects are followed by an aversive aftereffect that drives continued use. This study tested whether a 5-HT2A agonist (4-AcO-DMT, a psychedelic) follows that pattern in male rats. In a standard place-preference test 24 hours after dosing—when the drug had cleared—the rats showed no preference for the drug-paired location, suggesting no rewarding aftereffect. However, when the test was modified to capture only the acute drug effect, the rats did show a place preference, indicating the drug itself was rewarding. In a separate test measuring only the 24-hour aftereffect, that aftereffect also produced a strong place preference.
Neuroscience letters
May 23, 2025
Diane Joss, Gunes Sevinc, John W Denninger et al.
1 citation
Among 94 chronically stressed but otherwise healthy adults randomized to eight weeks of meditation, yoga, or stress education, only the meditation group showed a significant reduction in resting-state functional connectivity between the posterior cingulate cortex and the left hippocampus. Changes in this brain connectivity were correlated with improvements in perceived stress, allostatic load, and anti-inflammatory gene expression, suggesting that meditation's neural effects are closely linked to physical wellness biomarkers. No such changes occurred in the yoga or stress education groups, indicating this neurobiological mechanism may be unique to meditation training.