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 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
- serotoninové receptory 5-HT2 - antagonisté farmakologie 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
There are currently no pharmacological treatments for cocaine use disorder. Recently there has been a great deal of interest in the potential of psychedelic drugs such as psilocybin to treat psychiatric disorders. Human studies have indicated that a single administration of psilocybin can have long-lasting effects. Few preclinical studies have examined a role for psilocybin in addiction models. The goal of the current study was to determine whether psilocybin would enhance extinction following cocaine self-administration in male and female mice and rats and thus result in an attenuation of cue-induced drug-seeking. In experiments in mice, 16 female and 19 male mice underwent 8d of cocaine self-administration (0.5 mg/kg/infusion) and extinction training. Immediately following extinction trials, mice were injected with vehicle or 1.0 mg/kg psilocybin. Following the conclusion of extinction training, mice were tested for cue-induced reinstatement. In experiments in rats, 24 female and 23 male rats underwent 15d of cocaine self-administration (0.8 mg/kg/infusion) and extinction training. Immediately following extinction trials, rats were injected with vehicle, 1.0 mg/kg psilocybin, or 2.5 mg/kg psilocybin. Following the conclusion of extinction training, rats were tested for cue-induced reinstatement. Psilocybin administered following extinction trials had no effect, as both female and male mice and rats demonstrated significant cue-induced reinstatement. These data suggest that psilocybin is ineffective at altering cocaine-seeking behavior in the paradigm and doses used in the current study. It remains to be seen whether treatment with psilocybin under different conditions may be useful in the long-standing goal of finding pharmacotherapies to treat CUD.
- MeSH
- autoaplikace * MeSH
- chování při shánění drogy * účinky léků MeSH
- extinkce (psychologie) * účinky léků MeSH
- halucinogeny * farmakologie aplikace a dávkování MeSH
- inhibitory vychytávání dopaminu farmakologie aplikace a dávkování MeSH
- kokain * farmakologie aplikace a dávkování MeSH
- krysa rodu rattus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- operantní podmiňování účinky léků MeSH
- podněty * MeSH
- pohlavní dimorfismus MeSH
- poruchy spojené s užíváním kokainu farmakoterapie psychologie MeSH
- potkani Sprague-Dawley MeSH
- psilocybin * farmakologie aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- halucinogeny ekonomika terapeutické užití MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- nádory komplikace psychologie MeSH
- psilocybin * ekonomika terapeutické užití MeSH
- vyvíjení léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- novinové články MeSH
- rozhovory MeSH
- MeSH
- chronická nemoc MeSH
- duševní poruchy farmakoterapie MeSH
- Evropská unie MeSH
- financování organizované MeSH
- halucinogeny ekonomika terapeutické užití MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- paliativní péče MeSH
- psilocybin * ekonomika terapeutické užití MeSH
- umírající psychologie MeSH
- vážná nemoc MeSH
- vyvíjení léků * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- novinové články MeSH
Antibiotic resistance in staphylococcal strains and its impact on public health and agriculture are global problems. The development of new anti-staphylococcal agents is an effective strategy for addressing the increasing incidence of bacterial resistance. In this study, ethanolic extracts of Cannabis sativa L. made from plant parts harvested during the whole vegetation cycle under various nutritional treatments were assessed for in vitro anti-staphylococcal effects. The results showed that all the cannabis extracts tested exhibited a certain degree of growth inhibition against bacterial strains of Staphylococcus aureus, including antibiotic-resistant and antibiotic-sensitive forms. The highest antibacterial activity of the extracts was observed from the 5th to the 13th week of plant growth across all the nutritional treatments tested, with minimum inhibitory concentrations ranging from 32 to 64 μg/mL. Using HPLC, Δ9-tetrahydrocannabinolic acid (THCA) was identified as the most abundant cannabinoid in the ethanolic extracts. A homolog of THCA, tetrahydrocannabivarinic acid (THCVA), reduced bacterial growth by 74%. These findings suggest that the cannabis extracts tested in this study can be used for the development of new anti-staphylococcal compounds with improved efficacy.
- MeSH
- agonisté kanabinoidních receptorů farmakologie MeSH
- antibakteriální látky farmakologie MeSH
- Cannabis * MeSH
- ethanol farmakologie MeSH
- halucinogeny * farmakologie MeSH
- kanabinoidy * farmakologie MeSH
- rostlinné extrakty farmakologie MeSH
- Staphylococcus MeSH
- tetrahydrokanabinol farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
Alcohol Use Disorder (AUD) adversely affects the lives of millions of people, but still lacks effective treatment options. Recent advancements in psychedelic research suggest psilocybin to be potentially efficacious for AUD. However, major knowledge gaps remain regarding (1) psilocybin's general mode of action and (2) AUD-specific alterations of responsivity to psilocybin treatment in the brain that are crucial for treatment development. Here, we conducted a randomized, placebo-controlled crossover pharmaco-fMRI study on psilocybin effects using a translational approach with healthy rats and a rat model of alcohol relapse. Psilocybin effects were quantified with resting-state functional connectivity using data-driven whole-brain global brain connectivity, network-based statistics, graph theory, hypothesis-driven Default Mode Network (DMN)-specific connectivity, and entropy analyses. Results demonstrate that psilocybin induced an acute wide-spread decrease in different functional connectivity domains together with a distinct increase of connectivity between serotonergic core regions and cortical areas. We could further provide translational evidence for psilocybin-induced DMN hypoconnectivity reported in humans. Psilocybin showed an AUD-specific blunting of DMN hypoconnectivity, which strongly correlated to the alcohol relapse intensity and was mainly driven by medial prefrontal regions. In conclusion, our results provide translational validity for acute psilocybin-induced neural effects in the rodent brain. Furthermore, alcohol relapse severity was negatively correlated with neural responsivity to psilocybin treatment. Our data suggest that a clinical standard dose of psilocybin may not be sufficient to treat severe AUD cases; a finding that should be considered for future clinical trials.
- MeSH
- alkoholismus * diagnostické zobrazování farmakoterapie MeSH
- default mode network MeSH
- ethanol MeSH
- halucinogeny * farmakologie MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- mozek diagnostické zobrazování MeSH
- psilocybin farmakologie MeSH
- recidiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- MeSH
- Alzheimerova nemoc komplikace MeSH
- demence * etiologie farmakoterapie prevence a kontrola MeSH
- farmaceutický výzkum MeSH
- finanční podpora výzkumu jako téma MeSH
- halucinogeny terapeutické užití MeSH
- ketamin terapeutické užití MeSH
- kognitivní dysfunkce farmakoterapie MeSH
- senioři MeSH
- Check Tag
- senioři MeSH
- Publikační typ
- novinové články MeSH
- MeSH
- biologická terapie metody trendy MeSH
- duševně nemocní MeSH
- duševní poruchy * diagnóza etiologie farmakoterapie MeSH
- halucinogeny terapeutické užití MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- kongresy jako téma MeSH
- léková rezistence účinky léků MeSH
- lidé MeSH
- multiomika metody MeSH
- zotavení z duševní nemoci MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- novinové články MeSH
The article describes the nutmeg of a nutmeg tree (Myristica), which is used as a spice and traditional medicine but is also abused as an illicit drug. The main chemical components, namely myristicin, are described.
The article describes the nutmeg of a nutmeg tree (Myristica), which is used as a spice and traditional medicine but is also abused as an illicit drug. The main chemical components, namely myristicin, are described.
