Barbiturate tolerance: effects on GABA-operated chloride channel function

  title={Barbiturate tolerance: effects on GABA-operated chloride channel function},
  author={Andrea M. Allan and Xiaoying Zhang and Lisa D. Baier},
  journal={Brain Research},
Chronic pentobarbital administration alters γ‐aminobutyric acidA receptor α6‐subunit mRNA levels and diazepam‐insensitive [3H]Ro15‐4513 binding
Data suggest that chronic pentobarbital treatment induced expression of α6‐subunit mRNA, a major component of the diazepam‐insensitive [3H]Ro15‐4513 binding site, which implied de novo synthesis of the receptor subunit protein.
Pressure-sensitive and -insensitive coupling in γ-aminobutyric acida receptors
Abstract. Rationale: Previous behavioral and biochemical studies suggest that allosteric coupling processes initiated by benzodiazepines, barbiturates and neuroactive steroids can be sub-categorized
Ethanol increases GABAA responses in cells stably transfected with receptor subunits.
Analysis of data obtained from individual cells expressing alpha 1 beta 1-gamma 2L subunits showed considerable variability in sensitivity to ethanol, particularly with concentrations of 30 and 100 mM, suggesting the existence of ethanol-sensitive and -resistant receptors that may differ in subunit composition.
Use-dependent regulation of GABAA receptors.


Anesthetic and convulsant barbiturates alter gamma-aminobutyric acid-stimulated chloride flux across brain membranes.
  • A. Allan, R. Harris
  • Biology, Chemistry
    The Journal of pharmacology and experimental therapeutics
  • 1986
Evidence is provided for a functional coupling among GABA and barbiturate receptors and the chloride ionophore and suggest that the GABA-activated chloride channel is a site of action for intoxicant-anesthetic and convulsant barbiturates.
Chloride-dependent enhancement by barbiturates of gamma-aminobutyric acid receptor binding
  • R. Olsen, A. Snowman
  • Biology
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1982
The results suggest that there is a receptor site for barbiturates on the GABA receptor, and that the more physiological conditions of temperature and saline appear to be more suitable for physiologically relevant receptor binding studies in vitro.
Benzodiazepine agonist and inverse agonist actions on GABAA receptor-operated chloride channels. II. Chronic effects of ethanol.
  • K. Buck, R. Harris
  • Biology, Chemistry
    The Journal of pharmacology and experimental therapeutics
  • 1990
It is suggested that chronic exposure to ethanol reduces coupling between BZ agonist sites and the chloride channel, and may be responsible for the development of cross-tolerance between ethanol and Bz agonists.
Acute and chronic effects of pentobarbital in relation to postsynaptic GABA receptors: A study with muscimol
The results support the contention that pentobarbital (a) directly acts on the postsynaptic chloride ionophore and (b) augments GABA‐mediated post Synaptic effects.
Ethanol stimulates gamma-aminobutyric acid receptor-mediated chloride transport in rat brain synaptoneurosomes.
The ability of ethanol to stimulate GABA/barbiturate receptor-mediated Cl- transport may explain many of its pharmacological properties and provides a mechanism for the common psychopharmacological actions of ethanol, barbiturates, and benzodiazepines.
Chronic ethanol administration alters gamma-aminobutyric acid, pentobarbital and ethanol-mediated 36Cl- uptake in cerebral cortical synaptoneurosomes.
Data suggest that subsensitivity of the GABA receptor-coupled chloride ion channel after chronic ethanol administration may contribute to ethanol tolerance and the ethanol withdrawal syndrome.
GABA mediation of the central effects of acute and chronic ethanol in mice
  • M. Dar, W. Wooles
  • Medicine, Biology
    Pharmacology Biochemistry and Behavior
  • 1985