Search results for "Muscimol"
showing 10 items of 51 documents
Evidence that 3 alpha-hydroxy-5 alpha-pregnan-20-one is a physiologically relevant modulator of GABA-ergic neurotransmission.
1991
Abstract 3α-Hydroxy-5α-pregnan-20-one (HPO) is a progesterone metabolite which exhibits narcotic properties at high concentrations by interactions with the receptor for gamma-aminobutyric acid (GABA). The present investigation characterized low-dose effects of HPO on GABA A receptor binding, by determining the allosteric properties of HPO on the in vitro binding of 3 H-muscimol to membrane fractions from the cerebella of ovariectomized rats. A newly developed method for tissue preparation was used to wash out endogenous ligands interfering with the assay. HPO reduced the affinity of 3 H-muscimol to GABA A receptor sites by 52% and enhanced the number of accessible binding sites from 5.5±0.5…
Firing characteristics of vestibular nuclei neurons in the alert monkey after bilateral vestibular neurectomy
1992
After destruction of the peripheral vestibular system which is not activated by moving large-field visual stimulation, not only labyrinthine-ocular reflexes but also optokinetic-ocular responses related to the "velocity storage" mechanism are abolished. In the normal monkey optokinetic-ocular responses are reflected in sustained activity changes of central vestibular neurons within the vestibular nuclei. To account for the loss of optokinetic responses after labyrinthectomy, inactivation of central vestibular neurons consequent on the loss of primary vestibular activity is assumed to be of major importance. To test this hypothesis we recorded the neural activity within the vestibular nuclea…
Functional evidence for GABA as modulator of the contractility of the longitudinal muscle in mouse duodenum: Role of GABAA and GABAC receptors
2007
We investigated, in vitro, the effects of gamma-aminobutyric acid (GABA) on the spontaneous mechanical activity of the longitudinal smooth muscle in mouse duodenum. GABA induced an excitatory effect, consisting in an increase in the basal tone, which was antagonized by the GABA(A)-receptor antagonist, bicuculline, potentiated by (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid hydrate (TPMPA), a GABA(C)-receptor antagonist and it was not affected by phaclofen, a GABA(B)-receptor antagonist. Muscimol, GABA(A) receptor agonist, induced a contractile effect markedly reduced by bicuculline, tetrodotoxin (TTX), hexamethonium and atropine. Cis-4-aminocrotonic acid (CACA), a specific GABA(C) …
GABA-A receptoru agonista muscimola ietekme uz acetilholīna daudzumu Alcheimera slimības tipa modeļdzīvnieku smadzenēs
2017
Šī darba mērķis bija noskaidrot muscimola ļoti zemu devu (0,01 un 0,05 mg/kg) efektus uz acetilholīna šķelšanu intracerebroventrikulāras (i.c.v.) streptozocīna (STZ) ievadīšanas AD-tipa modelī. Rezultāti rāda, ka: 1.STZ i.c.v. ievadīšana izraisīja būtisku garozas un hipokampa AChE blīvuma palielinājumu. 2.Muscimols 0,01 un 0,05 mg/kg devās normalizēja AChE blīvumu STZ grupas žurku garozā un hipokampā līdz kontroles grupas līmenim. Iegūtie dati ļauj secināt, ka muscimola ļoti mazas devas regulē acetilholīna daudzumu i.c.v. STZ modelī. Iespējams, šis regulācijas mehānisms atbild par iepriekš novērotiem telpiskās atmiņas uzlabojumiem AD-tipa modeļdzīvniekos, tomēr ir nepieciešami tālāki pētīju…
GABAA agonista muscimola ietekme uz žurku atmiņu alcheimera slimības tipa modelī
2015
Darba mērķis bija noskaidrot GABAA agonista muscimola mazo devu ietekmi uz žurku atmiņu icv STZ AD tipa modelī. Lai noteiktu žurku iemācīšanos un atmiņu, tika veikti ūdens labirinta treniņtesti un fināla tests. Rezultāti rāda, ka icv STZ ievade žurkām izraisīja telpiskās atmiņas traucējumus. Muscimols abās devās (0,01 un 0,05 mg/kg) aizsargāja žurkas no STZ izraisītiem efektiem ūdens labirinta testā, uzlabojot to telpisko atmiņu, iemācīšanos un lokomotoro aktivitāti. Iegūtie dati ļauj secināt, ka muscimola mazo devu potenciāls ir intriģējošs jauno anti-AD terapiju izpētē un, ka būtu nepieciešama muscimola hronisko efektu izpēte minētajā modelī.
Age-related differences of γ-aminobutyric acid (GABA)ergic transmission in human colonic smooth muscle.
2021
Background: Enteric neurons undergo to functional changes during aging. We investigated the possible age-associated differences in enteric γ-aminobutyric acid (GABA)ergic transmission evaluating function and distribution of GABAergic receptors in human colon. Methods: Mechanical responses to GABA and GABA receptor agonists on slow phasic contractions were examined in vitro as changes in isometric tension in colonic muscle strips from young (<65 years old) and aged patients (>65 years old). GABAergic receptor expression was assessed by quantitative RT-PCR. Key Results: In both preparations GABA induced an excitatory effect, consisting in an increase in the basal tone, antagonized by th…
Assembly of functional α6β3γ2δ GABAA receptors in vitro
2000
Transgenic mice deficient in the alpha6 subunit of the GABA(A) receptor show reduced levels of the delta subunit protein and an altered GABA(A) receptor pharmacology, suggesting selective assembly mechanisms. Delta reduced the binding of [3H]Ro15-4513 or t-butylbicyclophosphoro[35S]thionate and, to a lesser extent, [3H]muscimol to recombinant alpha1beta1gamma2(delta), alpha4beta1gamma2(delta) and alpha6beta1gamma2(delta) receptors, paralleled by diminished GABA-evoked maximal currents in electrophysiological recordings for the latter one. The delta subunit gave rise to a lower EC50 for GABA and a slowed desensitization indicating its assembly in alpha6beta2delta, alpha6beta1gamma2delta and …
Fungal Hallucinogens Psilocin, Ibotenic Acid, and Muscimol
2013
Psychoactive drugs of fungal origin, psilocin, ibotenic acid, and muscimol among them have been proposed for recreational use and popularized since the 1960s, XX century. Despite their well-documented neurotoxicity, they reached reputation of being safe and nonaddictive. Scientific efforts to find any medical application for these hallucinogens in psychiatry, psychotherapy, and even for religious rituals support are highly controversial. Even if they show any healing potential, their usage in psychotherapy is in some cases inadequate and may additionally harm seriously suffering patients. Hallucinogens are thought to reduce cognitive functions. However, in case of indolealkylamines, such as…
Theoretical and experimental NMR studies on muscimol from fly agaric mushroom (Amanita muscaria)
2015
In this article we report results of combined theoretical and experimental NMR studies on muscimol, the bioactive alkaloid from fly agaric mushroom (Amanita muscaria). The assignment of (1)H and (13)C NMR spectra of muscimol in DMSO-d6 was supported by additional two-dimensional heteronuclear correlated spectra (2D NMR) and gauge independent atomic orbital (GIAO) NMR calculations using density functional theory (DFT). The effect of solvent in theoretical calculations was included via polarized continuum model (PCM) and the hybrid three-parameter B3LYP density functional in combination with 6-311++G(3df,2pd) basis set enabled calculation of reliable structures of non-ionized (neutral) molecu…
Neuroprotective action of diazepam at very low and moderate doses in Alzheimer's disease model rats
2018
Abstract Early manifestations of Alzheimer's disease (AD) include neuroinflammation, disrupted neurotransmission and cognitive deficits. Impairment of the GABAergic system is essentially involved in the pathogenesis of AD. Traditionally, agonists of GABAA receptors at doses above 1 mg/kg are known to possess memory impairing effects. However, we have previously found that GABAA receptor GABA site ligand muscimol at very low doses acted contrary – enhanced spatial learning/memory, as well as prevented neuroinflammation and augmented neurotransmission in AD model rats. Therefore, in the present study we focused on the assessment of the effects of non-sedative – very low (0.05 mg/kg) and moder…