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.
- Klíčová slova
- Locomotor activity, Mescaline, Sensorimotor gating, Serotonin receptors,
- 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
- práce podpořená grantem MeSH
- Názvy látek
- antagonisté serotoninových receptorů 5-HT2 MeSH
- antagonisté serotoninu MeSH
- halucinogeny MeSH
- meskalin * MeSH
- receptor serotoninový 5-HT2A * MeSH
- receptor serotoninový 5-HT2C * MeSH
Serotonergic psychedelics are recently gaining a lot of attention as a potential treatment of several neuropsychiatric disorders. Broadband desynchronization of EEG activity and disconnection in humans have been repeatedly shown; however, translational data from animals are completely lacking. Therefore, the main aim of our study was to assess the effects of tryptamine and phenethylamine psychedelics (psilocin 4 mg/kg, LSD 0.2 mg/kg, mescaline 100 mg/kg, and DOB 5 mg/kg) on EEG in freely moving rats. A system consisting of 14 cortical EEG electrodes, co-registration of behavioral activity of animals with subsequent analysis only in segments corresponding to behavioral inactivity (resting-state-like EEG) was used in order to reach a high level of translational validity. Analyses of the mean power, topographic brain-mapping, and functional connectivity revealed that all of the psychedelics irrespective of the structural family induced overall and time-dependent global decrease/desynchronization of EEG activity and disconnection within 1-40 Hz. Major changes in activity were localized on the large areas of the frontal and sensorimotor cortex showing some subtle spatial patterns characterizing each substance. A rebound of occipital theta (4-8 Hz) activity was detected at later stages after treatment with mescaline and LSD. Connectivity analyses showed an overall decrease in global connectivity for both the components of cross-spectral and phase-lagged coherence. Since our results show almost identical effects to those known from human EEG/MEG studies, we conclude that our method has robust translational validity.
- MeSH
- elektroencefalografie MeSH
- krysa rodu Rattus MeSH
- LSD * farmakologie MeSH
- meskalin * MeSH
- psilocybin analogy a deriváty farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- LSD * MeSH
- meskalin * MeSH
- psilocin MeSH Prohlížeč
- psilocybin MeSH
RATIONALE: Mescaline is a nonselective serotonin receptor agonist. It has relatively delayed onset of action and prolonged duration. Mescaline attenuates various behavioral parameters in rats; however, no information is available about its pharmacokinetics in rats and its relation to the behavioral changes produced by the drug. OBJECTIVES: The present study evaluates the spontaneous locomotor activity and sensorimotor gating in relation to mescaline concentrations in the serum and the brain of rats MATERIALS AND METHODS: Behavioral changes induced by mescaline [10, 20, and 100 mg/kg subcutaneously (s.c.)] were evaluated in an open-field test and testing of the prepulse inhibition of acoustic startle reaction (PPI) 15 and 60 min after drug administration. The time disposition of mescaline 20 mg/kg s.c. in rat serum and brain homogenates was analyzed by gas chromatography-mass spectrometry. RESULTS: Mescaline produced significant inhibitory effects on locomotion in low doses and a biphasic effect with the highest dose. In the PPI test, only when tested 60 min after drug administration, all doses of mescaline disrupted PPI. Besides the experimental protocol, we have observed that approximately 50% of animals receiving 100 mg/kg died within 12 h post-injection. The serum levels of mescaline rapidly increased within 30 min and subsequently quickly decreased; however, the brain concentrations reached a maximum 1 h after administration and remained high for an additional 60 min. CONCLUSIONS: Mescaline had a delayed onset of the main behavioral changes in rats compared to other hallucinogens. Behavioral changes correlated with the pharmacokinetics of the drug.
- MeSH
- časové faktory MeSH
- habituace (psychofyziologie) účinky léků MeSH
- halucinogeny farmakokinetika toxicita MeSH
- inhibice (psychologie) MeSH
- injekce subkutánní MeSH
- krysa rodu Rattus MeSH
- meskalin farmakokinetika toxicita MeSH
- metabolická clearance fyziologie MeSH
- mozek účinky léků metabolismus MeSH
- orientace účinky léků MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- pohybová aktivita účinky léků MeSH
- potkani Wistar 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
- práce podpořená grantem MeSH
- Názvy látek
- halucinogeny MeSH
- meskalin MeSH
Behavioural effects of two experimental neurotoxins, mescaline and DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine), on retention of spatial orientation were studied in the T-maze. The stereotaxic administration of both neurotoxins into the selected brain structures was chosen to reveal this effect. The intensity and time course of the neurotoxic effect were dependent on the brain area administered. Nevertheless, the lengthening of the latencies in reaching the goal was generally more marked after mescaline in comparison with DSP-4.
- MeSH
- benzylaminy farmakologie MeSH
- bludiště - učení účinky léků MeSH
- halucinogeny farmakologie MeSH
- krysa rodu Rattus MeSH
- meskalin farmakologie MeSH
- neurotoxiny farmakologie MeSH
- paměť účinky léků MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- benzylaminy MeSH
- DSP 4 MeSH Prohlížeč
- halucinogeny MeSH
- meskalin MeSH
- neurotoxiny MeSH
- MeSH
- inbrední kmeny potkanů MeSH
- katetrizace MeSH
- krysa rodu Rattus MeSH
- meskalin aplikace a dávkování farmakologie MeSH
- mozek MeSH
- operantní podmiňování účinky léků MeSH
- paměť účinky léků MeSH
- učení účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- meskalin MeSH
The central effect of mescaline and of its derivative N-[3,4,5- trimethoxyphenylethyl]-aziridine (FAZ) after their stereotaxic administration into the lateral ventricle of the brain was studied in behavioural experiments on rats. The effect of the two substances was tested by a method studying memory elicitation in response to appetitive motivation in a multiple T-maze. The results show that both substances worsened the behaviour in question. The negative effect of mescaline (lengthening of the time of passage through the maze) was manifested both immediately and several weeks after a single dose. FAZ likewise worsened the test reaction, but its effect was less pronounced than that of mescaline.
- MeSH
- aziridiny aplikace a dávkování farmakologie MeSH
- chování zvířat účinky léků MeSH
- inbrední kmeny potkanů MeSH
- injekce intraventrikulární MeSH
- krysa rodu Rattus MeSH
- meskalin aplikace a dávkování analogy a deriváty farmakologie MeSH
- orientace účinky léků MeSH
- paměť účinky léků MeSH
- prostorové chování * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- aziridiny MeSH
- meskalin MeSH
- MeSH
- aziridiny farmakologie MeSH
- cholinesterasové inhibitory farmakologie MeSH
- cholinesterasy krev metabolismus MeSH
- kinetika MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- meskalin metabolismus MeSH
- mozek účinky léků enzymologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- aziridiny MeSH
- cholinesterasové inhibitory MeSH
- cholinesterasy MeSH
- meskalin MeSH
- N-(3,4,5-trimethoxyphenylethyl)aziridine MeSH Prohlížeč
- MeSH
- lidé MeSH
- LSD farmakologie MeSH
- meskalin farmakologie MeSH
- vnímání času účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- LSD MeSH
- meskalin MeSH
- MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- meskalin farmakologie MeSH
- placebo MeSH
- psychiatrické posuzovací škály MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky kontrolované MeSH
- klinické zkoušky MeSH
- srovnávací studie MeSH
- Názvy látek
- meskalin MeSH
- placebo MeSH
- Klíčová slova
- EYE MANIFESTATIONS *, HALLUCINOGENS *, LYSERGIC ACID DIETHYLAMIDE *, MESCALINE *, PSILOCYBINE *, RORSCHACH TEST *, VISUAL PERCEPTION *,
- MeSH
- halucinogeny * MeSH
- lidé MeSH
- LSD * MeSH
- meskalin * MeSH
- oční nemoci * MeSH
- oční symptomy * MeSH
- psilocybin * MeSH
- Rorschachův test * MeSH
- zraková percepce * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- halucinogeny * MeSH
- LSD * MeSH
- meskalin * MeSH
- psilocybin * MeSH
