Locomotor response
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Psilocybin, a naturally occurring psychedelic compound in magic mushrooms, shows promise as a novel intervention with a single administration inducing rapid and long-lasting antidepressant effects. However, there are limited studies on the optimal dosing required for the beneficial effects of psilocybin given its side effects. To address this gap, we investigated in Wistar rats whether a single psilocybin administration (0.1, 0.32, 1.0, and 3.2 mg/kg) had antidepressant-like effects in the forced swim test (FST), a pro-social effect in the social interaction test (SIT), and the ability to alter pleasure using the sucrose preference test (SPT). We also examined the dose-response relationships of psilocybin on the head-twitch response (HTR), locomotor activity, body temperature, and weight gain. Furthermore, we explored whether the brain-derived neurotrophic factor (BDNF) levels in the hippocampus and prefrontal cortex (PFC) paralleled the behavioral changes observed after psilocybin. In the FST, psilocybin induced dose-dependent inverted-U-shaped responses with only the intermediate dose of 0.32 mg/kg producing short and long-term antidepressant-like effects. A similar pattern was observed for the SIT, the SPT, and the HTR. In contrast, the high doses of psilocybin (1.0 and 3.2 mg/kg), while deprived of anti-depressant-like activity, significantly reduced body temperature, locomotor activity, and body weight gain. BDNF levels in the hippocampus and PFC increased dose-dependently after psilocybin, but linearly suggesting a dissociation between high BDNF levels and the observed antidepressant-like behaviors. Our results indicated that there is a narrow window for the therapeutic potential of psilocybin, with 0.32 mg/kg effectively producing antidepressant-like effects without the accompanying adverse effects observed only at higher doses.
- MeSH
- antidepresiva * farmakologie terapeutické užití MeSH
- halucinogeny * farmakologie MeSH
- hipokampus účinky léků metabolismus MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- mozkový neurotrofický faktor metabolismus MeSH
- plavání psychologie MeSH
- pohybová aktivita účinky léků MeSH
- potkani Wistar MeSH
- prefrontální mozková kůra účinky léků metabolismus MeSH
- psilocybin * farmakologie terapeutické užití MeSH
- tělesná teplota účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Methoxphenidine (MXP) is classified as a new psychoactive substance that has recently emerged on the illicit drug market. Understanding the pharmacological and behavioural profiles of newly emerging drugs is essential for a better understanding of their psychotropic effects and potential toxicity. Therefore, in this study, we investigated a broad range of effects of acute MXP administration: pharmacokinetics in the brain and serum; behaviour (open field and prepulse inhibition), systemic toxicity (lethal dose; LD 50), and histopathology changes in parenchymal organs of Wistar rats. MXP rapidly crossed the blood-brain barrier, reaching peak median concentrations in both serum and brain 30 min post-administration, followed by an elimination phase with a half-life of 2.15 h. Locomotor activity in the open field test displayed a dose-response effect at low to moderate doses (10-20 mg/kg MXP). At higher doses (40 mg/kg), locomotor activity decreased. All doses of MXP significantly disrupted prepulse inhibition and the effect was present during the onset of its action as well as 60 min after treatment. Additionally, MXP demonstrated moderate acute toxicity, with an estimated LD50 of 500 mg/kg when administered subcutaneously. In summary, MXP exhibited a profile similar to typical dissociative anesthetics, producing stimulant and anxiogenic effects at lower doses, sedative effects at higher doses, and disrupting sensorimotor gating. The accumulation of MXP in brain tissue is likely to contribute to acute intoxication in humans, potentially leading to negative experiences. Our findings highlight the potentially dangerous effects of recreational MXP use and underscore the risks of inducing serious adverse health outcomes.
- MeSH
- chování zvířat účinky léků MeSH
- krysa rodu rattus MeSH
- LD50 MeSH
- mozek účinky léků metabolismus MeSH
- piperidiny farmakokinetika farmakologie MeSH
- pohybová aktivita účinky léků MeSH
- potkani Wistar * MeSH
- prepulsní inhibice účinky léků MeSH
- test otevřeného pole účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
RATIONALE: Mescaline is a classical psychedelic compound with a phenylethylamine structure that primarily acts on serotonin 5-HT2A/C receptors, but also binds to 5-HT1A and 5-HT2B receptors. Despite being the first psychedelic ever isolated and synthesized, the precise role of different serotonin receptor subtypes in its behavioral pharmacology is not fully understood. OBJECTIVES: In this study, we aimed to investigate how selective antagonists of 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT1A receptors affect the behavioral changes induced by subcutaneous administration of mescaline (at doses of 10, 20, and 100 mg/kg) in rats. METHODS: We used adult male Wistar rats in all our experiments. We evaluated locomotor activity using the open field test, and assessed sensorimotor gating deficits by measuring prepulse inhibition (PPI) of acoustic startle reaction (ASR). RESULTS: While the highest dose of mescaline induced hyperlocomotion (p < 0.001), which almost all the other antagonists reversed (p < 0.05-0.001), the PPI deficits were selectively normalized by the 5-HT2A antagonist (p < 0.05-0.01). The 5-HT2C antagonist partially reversed the small PPI deficit induced by lower doses of mescaline (p = 0.0017). CONCLUSION: Our findings suggest that mescaline-induced changes in behavior are primarily mediated by the 5-HT2A receptor subtype, with less pronounced contributions from the 5-HT2C receptor. The other antagonists had limited effects.
- MeSH
- antagonisté serotoninových receptorů 5-HT2 farmakologie MeSH
- antagonisté serotoninu farmakologie MeSH
- chování zvířat * účinky léků MeSH
- halucinogeny farmakologie aplikace a dávkování MeSH
- krysa rodu rattus MeSH
- lokomoce účinky léků MeSH
- meskalin * farmakologie MeSH
- pohybová aktivita účinky léků MeSH
- potkani Wistar * MeSH
- prepulsní inhibice účinky léků MeSH
- receptor serotoninový 5-HT2A * metabolismus účinky léků MeSH
- receptor serotoninový 5-HT2C * metabolismus účinky léků MeSH
- úleková reakce účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Spinal cord injury (SCI) often leads to central neuropathic pain, a condition associated with significant morbidity and is challenging in terms of the clinical management. Despite extensive efforts, identifying effective biomarkers for neuropathic pain remains elusive. Here we propose a novel approach combining matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with artificial neural networks (ANNs) to discriminate between mass spectral profiles associated with chronic neuropathic pain induced by SCI in female mice. Functional evaluations revealed persistent chronic neuropathic pain following mild SCI as well as minor locomotor disruptions, confirming the value of collecting serum samples. Mass spectra analysis revealed distinct profiles between chronic SCI and sham controls. On applying ANNs, 100% success was achieved in distinguishing between the two groups through the intensities of m/z peaks. Additionally, the ANNs also successfully discriminated between chronic and acute SCI phases. When reflexive pain response data was integrated with mass spectra, there was no improvement in the classification. These findings offer insights into neuropathic pain pathophysiology and underscore the potential of MALDI-TOF MS coupled with ANNs as a diagnostic tool for chronic neuropathic pain, potentially guiding attempts to discover biomarkers and develop treatments.
- MeSH
- biologické markery krev MeSH
- chronická bolest krev diagnóza etiologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- neuralgie * krev diagnóza etiologie MeSH
- neuronové sítě * MeSH
- poranění míchy * komplikace krev MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice * metody MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The choroid plexus (ChP) in the brain ventricles has a major influence on brain homeostasis. In this study, we aimed to determine whether the circadian clock located in ChP is affected by chronodisruption caused by misalignment with the external light/dark cycle and/or inflammation. Adult mPer2Luc mice were maintained in the LD12:12 cycle or exposed to one of two models of chronic chronodisruption - constant light for 22-25 weeks (cLL) or 6-hour phase advances of the LD12:12 cycle repeated weekly for 12 weeks (cLD-shifts). Locomotor activity was monitored before the 4th ventricle ChP and suprachiasmatic nuclei (SCN) explants were recorded in real time for PER2-driven population and single-cell bioluminescence rhythms. In addition, plasma immune marker concentrations and gene expression in ChP, prefrontal cortex, hippocampus and cerebellum were analyzed. cLL dampened the SCN clock but did not shorten the inactivity interval (sleep). cLD-shifts had no effect on the SCN clock, but transiently affected sleep duration and fragmentation. Both chronodisruption protocols dampened the ChP clock. Although immune markers were elevated in plasma and hippocampus, levels in ChP were unaffected, and unlike the liver clock, the ChP clock was resistant to lipopolysaccharide treatment. Importantly, both chronodisruption protocols reduced glucocorticoid signaling in ChP. The data demonstrate the high resistance of the ChP clock to inflammation, highlighting its role in protecting the brain from neuroinflammation, and on the other hand its high sensitivity to chronodisruption. Our results provide a novel link between human lifestyle-induced chronodisruption and the impairment of ChP-dependent brain homeostasis.
- MeSH
- chronická lymfatická leukemie * MeSH
- cirkadiánní hodiny * MeSH
- cirkadiánní proteiny Period genetika metabolismus MeSH
- cirkadiánní rytmus fyziologie MeSH
- lidé MeSH
- myši MeSH
- plexus chorioideus metabolismus MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Background: There is a paucity of literature on the effects of fitness programs such as CrossFit (CF), Les Mills (LM), and traditional resistance training (TRAD) on sensorimotor responses, which define overall motor skills levels that are major factors in improving quality of life of fitness training practitioners. Objective: The purpose of this study was to assess and compare the sensorimotor responses after 16 weeks of CF, LM and TRAD trainings. Methods: A total of one hundred and seven sedentary participants (81 men, 26 women, age 30.5 ± 5.7 years, weight 78.9 ± 11.1 kg, height 174.9 cm, fat mass 25.4 ± 5.3%) were assigned randomly into 3 groups CF (n = 34), LM (n = 33) and TRAD (n = 40), they followed the training allocated at the rate of 5 sessions/week for 16 weeks. On three occasions: before (T0), after eight (T1) and sixteen weeks (T2) of training, participants underwent different tests of sensorimotor measures; coordination (Extremity Motor Coordination Test), accuracy (Motor Accuracy Test), agility (Illinois Agility Test) and balance (Y Balance Test).Results: Coordination improved only in the LM group for upper (T0-T1: p < .001, d = 0.09-0.13; T1-T2: p < .001, d = 0.16-0.18) and lower limbs coordination (T0-T1: p < .001, d = 0.16-0.25; T1-T2: p < .001, d = 0.24-0.26). Agility test showed improvements for LM (T0-T1: p < .001, d = 0.55; T1-T2: p < .001, d = 0.87) and CF (T0-T1: p = .002, d = 0.20; T1-T2: p < .001, d = 0.40) and no difference for TRAD. For balance, results showed improvements in lower limbs for CF (T0-T1: p < .001, d = 0.08-0.14, T1-T2: p < .001, d = 0.05-0.23) and TRAD (T0-T1: p ≤ .003, d = 0.05-0.08, T1-T2: p < .001, d = 0.08-0.13) and at T2 for LM (p = 0.04, d = 0.06-0.2), for the upper limbs, results showed improvements for CF (T0-T1: p < .001, d = 0.04-0.09; T1-T2: p < .001, d = 0.15-0.28), at T2 for TRAD (p = .01-.03, d = 0.03-0.10) and no difference for LM. For motor accuracy, results did not show any difference. Conclusions: CF and LM trainings helps develop agility; however, CF and TRAD are more oriented to balance while LM are to coordination improvement, all three trainings have no effect on motor accuracy.
Lékař ošetřující potenciálního revmatologického pacienta často pracuje s omezeným počtem vstupních informací. Musí odhadnout rizika a správně nasměrovat pacienta k další péči do spádového zdravotnického zařízení nebo terciárního centra. V článku se proto zaměřujeme na typický klinický obraz vybraných urgentních stavů při systémových onemocněních pojiva a systémových vaskulitidách s cílem osvojit si přístup k nemocnému odpovídající této naléhavé situaci. Ve většině případů jde o zánětlivý stav spojený s postižením pohybového systému (zejm. artritidami), ale i jiných orgánů a systémů (srdce, plíce, ledviny, nervový systém a jiné), a/nebo teplotou. Většinu z nich spolehlivě diagnostikujeme kombinací běžných laboratorních, zobrazovacích a imunologických vyšetření, kdy je typický nález autoprotilátek většinou z okruhu ANA nebo ANCA. U jednotlivých systémových nemocí jsou rozebírány specifické naléhavé situace, jako je neurolupus, stavy asociované s trombotickou mikroangiopatií (sklerodermická renální krize, katastrofický antifosfolipidový syndrom), porucha polykání s rizikem aspirace, přední ischemická neuropatie optického nervu a syndrom difúzní alveolární hemoragie. Jejich naléhavost spočívá mimo jiné v tom, že se může jednat o vůbec první projev dosud nediagnostikovaného systémového onemocnění. Mají vysokou mortalitu a špatnou prognózu, nejsou-li diagnostikovány a léčeny dostatečně rychle. Zlatým standardem v terapii zůstávají vysokodávkované pulzy intravenózních glukokortikoidů. Je vždy obtížné, složité a zodpovědné být mezi prvními na cestě k poznání závažné naléhavé diagnózy. Snadněji se kráčí připraveným.
A physician treating a potential rheumatology patient often works with a limited amount of information. They must assess the risks and correctly refer the patient for further care to the regional healthcare facility or tertiary center. In this article, we therefore focus on the typical clinical picture of selected emergency conditions in connective tissue diseases and systemic vasculitis with the aim of adopting an approach to the patient corresponding to this urgent situation. In most cases, it is an inflammatory condition associated with the involvement of the locomotor system (especially arthritis), but also other organs and systems (heart, lungs, kidneys, nervous system and others), and/or fever. Most of them are reliably diagnosed by a combination of common laboratory, imaging and immunological examinations, where the typical finding of autoantibodies is mostly from the ANA or ANCA family. For individual systemic diseases, specific emergency situations are discussed, such as neurolupus, conditions associated with thrombotic microangiopathy (scleroderma renal crisis, catastrophic antiphospholipid syndrome), swallowing disorder with risk of aspiration, anterior ischemic optic neuropathy, and diffuse alveolar hemorrhage syndrome. Their urgency lies, among other things, in the fact that this may be the very first manifestation of a systemic disease that has not been diagnosed yet. They have a high mortality rate and a poor prognosis if not diagnosed and treated quickly enough. High-dose pulses of intravenous glucocorticoids remain the gold standard for treatment. It is always difficult, complex and responsible to be among the first on the way to knowing a serious emergency diagnosis. It is easier to walk prepared.
Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disorder with high prevalence among middle-aged women. Collagen-induced arthritis (CIA) is the most widely used animal model of RA, however, sex differences and long-term effects of CIA in mice are poorly described in the literature. Aim: Therefore, the present study aimed to analyze the long-term effects of CIA on the joints of middle-aged mice of both sexes and to describe potential sex differences. Materials and methods: CIA was induced in middle-aged DBA/1J mice by immunization with bovine type II collagen and complete Freund's adjuvant. Saline was administered to control mice. Arthritis score assessment, plethysmometry, and thermal imaging of the joints were performed weekly for 15 weeks. Locomotor activity, micro-computed tomography, joint histology and biochemical analyses were performed at the end of the experiment. Results: Our results indicate a similar prevalence of arthritis in both sexes of mice-67% (8/12) of females and 89% (8/9) males with an earlier onset in males (day 14 vs. day 35). After the arthritis scores peaked on day 56 for males and day 63 for females, they steadily declined until the end of the experiment on day 105. A similar dynamics was observed in paw volume and temperature analyzing different aspects of joint inflammation. Long-term consequences including higher proteinuria (by 116%), loss of bone density (by 33.5%) and joint damage in terms of synovial hyperplasia as well as bone and cartilage erosions were more severe in CIA males compared to CIA females. There were no significant differences in locomotor activity between CIA mice and CTRL mice of any sex. Conclusion: This is the first study to describe the long-term effects of the CIA model in terms of sex differences in DBA/1J mice. Our results indicate sex differences in the dynamics, but not in the extent of arthritis. An earlier onset of arthritis and more severe consequences on joints, bones and kidneys were found in males. The underlying immune pathomechanisms responsible for the limited duration of the arthritis symptoms and the opposite sex difference in comparison to RA patients require further investigation.
- Publikační typ
- časopisecké články MeSH
Previous evidence suggests that prenatal exposure to THC (pTHC) derails the neurodevelopmental trajectories towards a vulnerable phenotype for impaired emotional regulation and limbic memory. Here we aimed to investigate pTHC effect on hippocampus-related cognitive functions and markers of neuroplasticity in adolescent male offspring. Wistar rats were exposed to THC (2 mg/kg) from gestational day 5 to 20 and tested for spatial memory, object recognition memory and reversal learning in the reinforce-motivated Can test and in the aversion-driven Barnes maze test; locomotor activity and exploration, anxiety-like behaviour, and response to natural reward were assessed in the open field, elevated plus maze, and sucrose preference tests, respectively. The gene expression levels of NMDA NR1-2A subunits, mGluR5, and their respective scaffold proteins PSD95 and Homer1, as well as CB1R and the neuromodulatory protein HINT1, were measured in the hippocampus. pTHC offspring exhibited deficits in spatial and object recognition memory and reversal learning, increased locomotor activity, increased NR1-, decreased NR2A- and PSD95-, increased mGluR5- and Homer1-, and augmented CB1R- and HINT1-hippocampal mRNA levels. Our data shows that pTHC is associated with specific impairment in spatial cognitive processing and effectors of hippocampal neuroplasticity and suggests novel targets for future pharmacological challenges.
- Publikační typ
- časopisecké články MeSH
N-(2-methoxybenzyl)phenethylamines (NBOMes) are a family of potent 5-HT2A agonists containing substances emerging on the illicit drug market as a replacement for N,N-diethyllysergamide (LSD). Despite the increasing use of NBOMes for diagnostic, research and recreational purposes, only a limited number of studies have focussed on their in vivo effect. Here, we investigated pharmacokinetics, systemic toxicity, thermoregulation in individually and group-housed animals, and acute behavioural effects after subcutaneous administration of 2,5-dimethoxy-4-(2-((2-methoxybenzyl)amino)ethyl)benzonitrile (25CN-NBOMe; 0.2, 1, and 5 mg/kg) in Wistar rats. Drug concentration peaked 1 h after the administration of 5 mg/kg in both blood serum and brain tissue with a half-life of 1.88 and 2.28 h, respectively. According to Organisation for Economic Co-operation and Development 423 toxicity assay, the drug is classified into category 3 with a lethal dose of 300 mg/kg and an estimated LD50 value of 200 mg/kg. Histological examination of organs collected from rats injected with the lethal dose revealed subtle pathological changes, highly suggestive of acute cardiovascular arrest due to malignant arrhythmia. Altered thermoregulation after 5 mg/kg was demonstrated by reduced body temperature in individually housed rats (p < 0.01). Behavioural effects assessed by the Open Field test and Prepulse Inhibition of Startle Response revealed that the two lower doses (0.2 and 1 mg/kg) caused a reduction in locomotor activity (p < 0.01), increased anxiety (p < 0.05) and 5 mg/kg additionally impaired sensorimotor gating (p < 0.001). In summary, 25CN-NBOMe readily passes the blood-brain barrier and exhibits a moderate level of toxicity and behavioural effect comparable with other NBOMes.
