We used two mouse lines with glycine receptor mutations to determine whether glycine receptors might play an important role in anesthetic responses in vivo. Spastic (spA) mutants were slightly more sensitive (P = 0.02) to enflurane in the loss-of-righting reflex assay (50% effective concentration [EC(50)] = 1.17 +/- 0.06 atm for controls versus 0.97 +/- 0.06 atm for spA) but were also substantially more resistant (P = 0.01) to enflurane in the tail clamp assay (EC(50) = 1.96 +/- 0.10 atm for controls versus 2.58 +/- 0.25 atm for spA).
We studied the effects of pentobarbital and antagonists of glutamate, gamma-aminobutyrate (GABA), and glycine receptors on extracellular activity in ventrobasal thalamic slices. Pentobarbital at sedative-hypnotic concentration (20 microM) reversibly induced 1-15 Hz oscillations. Sustained oscillations required electrical stimulation of internal capsule, but not elevated temperature or low [Mg2+]. Anesthetic concentration (200 microM) of pentobarbital evoked only transient oscillations. Kynurenate-sensitive glutamate receptors were essential for oscillations.
Ethyl 2-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-4-imidazolecarboxylate (TG41) enhanced the binding both of gamma-aminobutyric acid (GABA) and of flunitrazepam to rat cerebral cortical membranes. Electrophysiological recordings from Xenopus oocytes expressing various recombinant GABA(A) receptor subtypes revealed that TG41 enhanced the function of all receptor subunit combinations tested. The potency of TG41 at receptors containing alpha1, beta2, and gamma2L subunits was greater than that of alphaxalone, etomidate, propofol, or pentobarbital.
The present study was designed to investigate the role of strychnine-sensitive glycine receptors in hypnosis and analgesia induced by emulsified volatile anesthetics. After having established the mice model of hypnosis and analgesia by intraperitoneally injecting (i.p.) appropriate doses of ether, enflurane, isoflurane or sevoflurane, we intracerebroventricularly (i.c.v.) or intrathecally (i.t.) injected different doses of strychnine and then observed the effects on the sleeping time using the awaken test and the pain index in hot-plate test (HPPI) using the hot-plate test.
BACKGROUND: It is well documented that several general anesthetics, including propofol, potentiate glycine receptor function. Furthermore, glycine receptors exist throughout the central nervous system, including areas of the brain thought to be involved in sleep. However, the role of glycine receptors in anesthetic-induced hypnosis has not been determined. METHODS: Experiments were conducted in rats where the loss of righting reflex (LORR) was used as a marker of the hypnotic state.
BACKGROUND: Glycine is a major inhibitory neurotransmitter in the adult central nervous system (CNS), and its receptors (GlyRs) are well known for their effects in the spinal cord and the lower brainstem. Accumulating evidence indicates that GlyRs are more widely distributed in the CNS, including many supraspinal regions. Previous in vitro studies have demonstrated that ethanol potentiates the function of these brain GlyRs, yet the behavioral role of the brain GlyRs has not been well explored. METHODS: Experiments were conducted in rats.
Strychnine-sensitive glycine receptors (GlyR) play a major role in the excitability of CNS neurons and are also a major target of many drugs including some general anesthetics and ethanol. The prefrontal cortex (PFC) is an important substrate responsible for cognitive function and for sedation, as well as hypnosis (unconsciousness) which is induced by general anesthetics and ethanol. However, the functions and the physiological and pharmacological properties of GlyRs in mature PFC neurons have not been well studied.
In Ayurveda,Withania somnifera (WS) is used as a medicine to maintain mental and physical health as well as to enhance memory. In this study, the methanolic extract of WS(mWS) was tested for its electrical influence on hippocampal CA1 pyramidal neurons using a patch clamp technique. In current clamp mode under a high chloride pipette solution, mWS (400 ng/μl) induced remarkable membrane depolarization (9.75 ± 2.54 mV, n = 6) of CA1 neurons. The mWS-induced depolarization was dose-dependent, reproducible, and persistent in the presence of 0.5 μM tetrodotoxin (TTX, 10.17 ± 0.04 mV, n = 6).
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience
GABA-mediated postsynaptic currents (IPSCs) were recorded from dopaminergic (DA) neurons of the ventral tegmental area (VTA) of rats, in acute brain slices, and from enzymatically or mechanically dissociated neurons. In young rats (3-10 d of age), where GABA is excitatory, glycine (1-3 microm) and taurine (10-30 microm) increased the amplitude of evoked IPSCs (eIPSCs) and the frequency of spontaneous IPSCs (sIPSCs) but had minimal postsynaptic effects.
The physiological and pharmacological properties of taurine-induced responses were investigated in dopaminergic (DA) neurones from the ventral tegmental area (VTA) of young rats aged 1-13 postnatal days, either in acute brain slices or acutely dissociated neurones. When whole-cell responses were recorded from current-clamped neurones using the gramicidin-perforated technique, the application of taurine (0.01-30 mm) accelerated firings and induced membrane depolarization.