Picrotoxin and bicuculline have different effects on lumbar spinal networks and motoneurons in the neonatal rat

Bicuculline is the most commonly used GABA A receptor antagonist to investigate the contribution of these receptors in motor control. However, this compound has been shown recently to potentiate the burst firing of neurons in various brain regions by blocking a calcium-activated potassium current un...

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Veröffentlicht in:Brain research 2002-05, Vol.935 (1), p.81-86
Hauptverfasser: Pflieger, Jean-François, Clarac, François, Vinay, Laurent
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description Bicuculline is the most commonly used GABA A receptor antagonist to investigate the contribution of these receptors in motor control. However, this compound has been shown recently to potentiate the burst firing of neurons in various brain regions by blocking a calcium-activated potassium current underlying the spike after-hyperpolarization (AHP). This effect may distort our understanding of the role of GABA A receptors at the network level. In vitro brainstem-spinal cord preparations isolated from neonatal rats were used to compare the effects of bicuculline methiodide (bicuculline-M) and picrotoxin (PTX), another GABA A receptor antagonist, on the AHP of lumbar motoneurons as well as on spontaneous and locomotor-like motor activities. Intracellular recordings of lumbar motoneurons showed that bicuculline-M (20 μM) reduced the AHP to 57% of control whereas PTX (20–60 μM) had no significant effect. Bath-application of increasing concentrations of PTX caused an increase in spontaneous ventral root activity, which further increased significantly when bicuculline-M was added. The effects of both antagonists were tested on fictive locomotion. The left–right alternation was disrupted in the presence of bicuculline-M. A slow synchronous bursting activity of large amplitude also appeared in the presence of PTX. This slow rhythm was superimposed on a faster rhythm which still exhibited some degree of left–right alternation. These data demonstrate that bicuculline-M may not reveal accurately the contribution of GABA A receptors in motor control and the intrinsic properties of disinhibited networks.
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subjects 2-Amino-5-phosphonovalerate - pharmacology
6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology
Action Potentials - drug effects
Action Potentials - physiology
Animals
Animals, Newborn
Bicuculline
Bicuculline - pharmacology
Biological and medical sciences
Central pattern generator
Disinhibition
Excitatory Amino Acid Antagonists
Fundamental and applied biological sciences. Psychology
GABA A receptor
GABA Antagonists - pharmacology
GABA-A Receptor Antagonists
gamma-Aminobutyric Acid - metabolism
Interneurons - cytology
Interneurons - drug effects
Interneurons - metabolism
Locomotion
Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration
Motor Neurons - cytology
Motor Neurons - drug effects
Motor Neurons - metabolism
Nerve Net - cytology
Nerve Net - drug effects
Nerve Net - metabolism
Neural Inhibition - drug effects
Neural Inhibition - physiology
Neural Pathways - cytology
Neural Pathways - drug effects
Neural Pathways - metabolism
Picrotoxin - pharmacology
Rats
Rats, Wistar
Receptors, GABA-A - metabolism
Spinal Cord - cytology
Spinal Cord - drug effects
Spinal Cord - metabolism
Synaptic Transmission - drug effects
Synaptic Transmission - physiology
Vertebrates: nervous system and sense organs
title Picrotoxin and bicuculline have different effects on lumbar spinal networks and motoneurons in the neonatal rat
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