Pentobarbital induces thalamic oscillations in brain slices, modulated by GABA and glycine receptors.
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. GABA(A) antagonism (bicuculline, 50 microM or gabazine, 20 microM) suppressed oscillations at 5-15 Hz. GABA(B) antagonism (CGP 35348, 100 nM), or antagonism of glycine receptors (strychnine, 1 microM) suppressed oscillations at 1-4 and 11-15 Hz. GABA and glycine receptors modulated oscillation frequency. For elimination, oscillations required GABA antagonists and strychnine. Receptors for glutamate and glycine mediated oscillations during GABA receptor blockade in ventrobasal nuclei, or on disconnection from nRT. Glycine receptors were critical for oscillations in dorsal thalamic network, divested of GABAergic inhibition. Glutamate and GABA receptors mediated pentobarbital-induced oscillations in nRT, disconnected from ventrobasal nuclei. Hence, pentobarbital oscillogenesis occurred in isolated networks of the ventrobasal and reticularis nuclei mediated by glutamate receptors, with frequency modulation by GABA(A), GABA(B), and glycine receptors. These stationary oscillations represent a model of sedation-hypnosis, amenable to pharmacological analysis.
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Department of Pharmacology and Therapeutics, The University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.
Mathers
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D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D005583:Fourier Analysis; D018756:GABA Antagonists / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D009415:Nerve Net / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D018079:Receptors, GABA / Q000187:drug effects*; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013331:Strychnine / Q000494:pharmacology; D013788:Thalamus / Q000187:drug effects*
D018756:GABA Antagonists; D018684:Glycine Agents; D006993:Hypnotics and Sedatives; D009943:Organophosphorus Compounds; D011724:Pyridazines; D018079:Receptors, GABA; D018009:Receptors, Glycine; C066430:CGP 35348; C049853:gabazine; D013331:Strychnine; D010424:Pentobarbital