Experimental Neurology
February 1, 1984
K Rasmussen, J Heym, B L Jacobs
125 citations
Serotonergic neurons in the nucleus centralis superior (NCS) of freely moving cats fire most rapidly during active waking (mean 2.94 spikes/s), slow down during slow-wave sleep (mean 1.38 spikes/s), and are least active during REM sleep (mean 0.46 spikes/s). Their activity does not increase with transient muscle movements but decreases just before and during sleep spindles. Most NCS serotonergic neurons are excited by sudden sounds or lights. A serotonin-like drug reduces their firing by about 44%. A subset of these neurons shows much smaller changes across sleep-wake states and is inhibited, rather than excited, by sensory stimuli. These patterns are compared with serotonergic neurons in other brain regions.
Experimental Neurology
February 14, 2020
Sándor Nardai, Marcell J László, Attila Szabo et al.
91 citations
A single intraperitoneal dose of DMT (1 mg/kg) followed by a 24-hour infusion (2 mg/kg/h) reduced ischemic brain lesion volume and improved functional recovery in male Wistar rats after 60 minutes of transient middle cerebral artery occlusion. The neuroprotective effect was blocked by a Sigma-1 receptor antagonist, indicating a Sigma-1 receptor-dependent mechanism. DMT treatment lowered expression of the pro-apoptotic protein APAF1, increased brain-derived neurotrophic factor (BDNF), and shifted the inflammatory cytokine profile toward an anti-inflammatory state (decreased TNF-α, IL-1β, IL-6; increased IL-10). The findings suggest DMT protects against ischemic injury through combined anti-apoptotic, pro-neurotrophic, and anti-inflammatory actions.
Experimental Neurology
October 1, 2021
Giulia Costa, Krystyna Gołembiowska
64 citations
MDMA, also known as ecstasy, can cause acute and lasting abnormalities in the brain, as shown in both animal and human studies. Neurotoxic effects have been demonstrated in experimental animals, raising concerns about serious harm to health, especially since MDMA is used recreationally by young and adult people. This review summarizes recent findings on MDMA's central effects and the mechanisms behind its neurotoxicity.
Experimental Neurology
May 1, 2021
Fabrizio Schifano, Stefania Chiappini, Andrea Miuli et al.
49 citations
Several new psychoactive substances (NPS) can trigger serotonin syndrome, a dangerous condition of excessive serotonin activity marked by altered mental status, neuromuscular effects, and autonomic hyperactivity. A systematic review of three retrospective studies, two case series, and five case reports identified implicated substances including psychedelic phenethylamines (2C-I, 25I-NBOMe, 5-IT) and synthetic cathinones (mephedrone, MDPV, methylone, butylone, NRG3, AMT, MXP), as well as the antidepressant bupropion when misused at high doses or combined with other serotonergic drugs. Most substances were taken orally, though nasal insufflation and sublingual administration occurred. Psychiatric history was negative for most subjects. Clinicians should recognize NPS risks and diagnostic challenges due to undetectability in routine drug screenings.
Experimental Neurology
June 4, 2021
Deborah Rudin, Matthias E. Liechti, Dino Luethi
48 citations
New psychoactive stimulants and psychedelics affect monoaminergic systems through different mechanisms: stimulants interact with monoamine transporters, while psychedelics act mainly as agonists at serotonin 5-HT2A receptors. Both types have been linked to neurological and cognitive impairments. In vitro and rodent studies suggest mechanisms such as cytotoxicity, mitochondrial dysfunction, and oxidative stress may contribute to neurotoxicity from stimulants, and serotonin 5-HT2A receptor-mediated toxicity and apoptosis pathways may contribute to neurotoxicity from psychedelics. It remains unclear how well these preclinical findings translate to humans.
Experimental Neurology
June 1, 2022
I. Ornelas, F. A. Cini, Isabel Wießner et al.
37 citations
LSD treatment improved performance in a novel object recognition task in rats and a visuo-spatial memory task in humans. A proteomic analysis of human brain organoids showed that LSD affected metabolic pathways associated with neural plasticity, including mTOR. Simulations using a neural network model of a cortico-hippocampal circuit, with baseline plasticity strength as a proxy for age and increased plasticity related to LSD dose, fit the experimental data well. The results suggest that LSD has nootropic effects.
Experimental Neurology
April 1, 2020
Jessica Winne, Barbara C Boerner, Thawann Malfatti et al.
34 citations
Salicylate intoxication, which causes tinnitus and anxiety in humans, induces anxiety-like behavior and a specific brain oscillation called type 2 theta (theta2) in the hippocampus of young mice with normal hearing, but not in older mice. A single dose of the hallucinogenic compound 5-MeO-DMT prevents both the anxiety-like behavior and the increase in theta2 and slow gamma oscillations in the ventral hippocampus and medial prefrontal cortex after salicylate injection. These findings suggest that the anxiety triggered by salicylate depends on normal hearing and that hallucinogenic compounds may be effective for treating tinnitus-related anxiety.
Experimental Neurology
November 1, 2021
Matteo Marti, Giuseppe Talani, Cristina Miliano et al.
6 citations
Methoxetamine (MXE), a ketamine-like designer drug, alters serotonin levels in the rat medial prefrontal cortex and nucleus accumbens. Blocking serotonin 5-HT2 receptors with selective antagonists attenuated MXE's motor and sensory effects and prevented its reduction of prepulse inhibition, indicating these receptors are key to MXE's sensorimotor actions. In vitro, MXE inhibited NMDA-mediated field potentials and GABA-mediated spontaneous currents in a concentration-dependent manner but did not affect AMPA components or presynaptic glutamate release. The findings suggest MXE acts as an NMDA receptor antagonist, with 5-HT2 receptors crucial for its sensorimotor effects and NMDA and GABA receptors as additional targets.
Experimental Neurology
July 1, 2025
Mengqin Shan, Chaoyang Tong, Xin Fu et al.
2 citations
S-ketamine anesthesia in neonatal rats causes a drop in thyroid hormone levels and disrupts myelination, particularly by impairing the differentiation of oligodendrocyte precursor cells into mature oligodendrocytes. This leads to motor coordination deficits. Supplementing with triiodothyronine (T3) reverses these effects by restoring PPARα activity, a key regulator of lipid metabolism. Blocking PPARα with GW6471 eliminates T3's protective effect, while activating PPARα with fenofibrate rescues both coordination and cell maturation. The findings suggest that thyroid hormone supplementation could prevent anesthesia-related white matter damage in infants.
Experimental Neurology
September 1, 2026
Javier Calleja‐conde, Víctor Echeverry‐alzate, Marina Sanz-Sancristóbal et al.
In a preclinical model of Parkinson's disease, the compound N,N-dimethyltryptamine (DMT), the main psychoactive ingredient in ayahuasca, reduced neuroinflammation and preserved neurons in the nigrostriatal pathway. Treated animals also showed improvements in behavior. These results suggest DMT may have disease-modifying potential for Parkinson's disease, a progressive neurodegenerative disorder marked by loss of dopaminergic neurons and chronic inflammation, for which current treatments only relieve symptoms.
Experimental Neurology
September 3, 2020
A. Camargo, A. P. Dalmagro, M. M. de Souza et al.
A single injection of ketamine given a week before stress prevented depressive-like behavior in mice, while guanosine did not. The stressor, corticosterone, reduced proteins linked to synapse health in the hippocampus, and ketamine blocked that reduction. Combining low doses of ketamine and guanosine partly prevented one measure of depressive-like behavior. Fluoxetine given for three weeks did not prevent the stress effects. The findings suggest ketamine's lasting protective effect against depression involves pro-synaptogenic signaling in the hippocampus.