Parkinson's disease is a progressive neurodegenerative disorder with increasing global prevalence, primarily driven by population ageing. A hallmark of the disease is the degeneration of nigrostriatal dopaminergic neurons, accompanied by marked activation of glial cells and a sustained neuroinflammatory response. Current pharmacological treatments are limited to symptomatic relief and do not...
Growing evidence suggests that prolonged or repeated exposure to general anesthesia is associated with white matter alteration in children, which may underlie subsequent cognitive and behavioral abnormalities. Numerous infants undergo anesthesia for surgery each year, so it is imperative to identify the risk factors and find preventative treatment to prevent the effects of early anesthesia...
The therapeutic use of classical psychedelic substances such as d-lysergic acid diethylamide (LSD) surged in recent years. Studies in rodents suggest that these effects are produced by increased neural plasticity, including stimulation of the mTOR pathway, a key regulator of metabolism, plasticity, and aging. Could psychedelic-induced neural plasticity be harnessed to enhance cognition? Here we...
Methoxetamine (MXE) is a dissociative substance of the arylcyclohexylamine class that has been present on the designer drug market as a ketamine-substitute since 2010. We have previously shown that MXE (i) possesses ketamine-like discriminative and positive rewarding effects in rats, (ii) affects brain processing involved in cognition and emotional responses, (iii) causes long-lasting...
Preclinical and clinical studies indicate that 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy'), in addition to having abuse potential, may elicit acute and persistent abnormalities of varying severity at the central level. Importantly, neurotoxic effects of MDMA have been demonstrated in experimental animals. Accordingly, central toxicity induced by MDMA may pose a serious harm for health,...
New psychoactive stimulants and psychedelics continue to play an important role on the illicit new psychoactive substance (NPS) market. Designer stimulants and psychedelics both affect monoaminergic systems, although by different mechanisms. Stimulant NPS primarily interact with monoamine transporters, either as inhibitors or as substrates. Psychedelic NPS most potently interact with...
The use of several new psychoactive substances (NPS) has become very popular and is posing global health risks. Chemically and pharmacologically diverse molecules are constantly emerging and are presenting with a wide range of clinical implications. Serotonin toxicity, and specifically Serotonin Syndrome (SS), might develop as a result of an over-activation of the serotoninergic system caused...
Ketamine has been reported to exert a prophylactic effect against stress-induced depressive-like behavior by modulating the guanosine-based purinergic system. However, the molecular pathways underlying its prophylactic effect and whether guanosine also elicits a similar effect remain to be determined. Here, we investigated the prophylactic effect of ketamine and guanosine against corticosterone...
Salicylate intoxication is a cause of tinnitus and comorbidly associated with anxiety in humans. In a previous work, we showed that salicylate induces anxiety-like behavior and hippocampal type 2 theta oscillations (theta2) in mice. Here we investigate if the anxiogenic effect of salicylate is dependent on age and previous tinnitus experience. We also tested whether a single dose of DMT can...
Background and purposeN,N-dimethyltryptamine (DMT) is an endogenous ligand of the Sigma 1 receptor (Sig-1R) with documented in vitro cytoprotective properties against hypoxia. Our aim was to demonstrate the in vivo neuroprotective effect of DMT following ischemia-reperfusion injury in the rat brain.MethodsTransient middle cerebral occlusion (MCAO) was induced for 60 min in male Wistar rats...
Developing cannabinoid-based medication along with marijuana's recreational use makes it important to investigate molecular adaptations the endocannabinoid system undergoes following prolonged use and withdrawal. Repeated cannabinoid administration results in development of tolerance and produces withdrawal symptoms that may include seizures. Here we employed electrophysiological and...
The effects of (+/-)3,4-methylenedioxyamphetamine (MDA) were studied in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac, using the two-electrode voltage-clamp method. The RP4 neuron generated spontaneous action potentials. Extracellular or intracellular application of MDA elicited action potential bursts of the central RP4 neuron. The action potential bursts elicited...
Noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists, inclu ding ketamine and phencyclidine (PCP), produce abnormal intracellular vacuoles in posterior cingulate and retrosplenial cortical neurons in the rat. Ketamine also induces 70-kDa heat shock protein (HSP70) expression in pyramidal neurons in the posterior cingulate and retrosplenial cortex and, as shown by this study,...
Serotonergic neurons were recorded in the nucleus centralis superior (NCS) in freely moving cats and were initially identified on-line by their slow and regular spontaneous activity (mean 2.55 +/- 0.21 spikes/s). Discharge rates of NCS serotonergic neurons were highest during active waking (AW) (mean 2.94 +/- 0.28 spikes/s), decreased during slow-wave sleep (middle of SWS: mean 1.38 +/- 0.18...