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 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 microM) reduced the AHP to 57% of control whereas PTX (20-60 microM) 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.
Pflieger
Jean François
JF
DPM, CNRS, 31 chemin Joseph Aiguier, F-13402 Marseille Cedex 20, France.
Clarac
François
F
Vinay
Laurent
L
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009415:Nerve Net / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010852:Picrotoxin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001640:Bicuculline; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D010852:Picrotoxin; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid