A GABAergic component in homosynaptic depression in the spinal monosynaptic pathway. A requirement for action of benzodiazepines.
Spinal monosynaptic responses, evoked by repetitive stimulation, undergo homosynaptic depression the pattern of which is altered by 0.5 mg/kg of clonazepam. The dependence of this effect of clonazepam on the GABAergic system was examined in spinal unanaesthetized cats. Topical application of bicuculline to the spinal cord did not change any feature of the homosynaptic depression in the biceps-semitendinosus (BST) or triceps surae (TS) monosynaptic pathway but antagonized the action of clonazepam. Semicarbazide (200 mg/kg, i.v.) also prevented the effect of the benzodiazepine but alone had actions of its own. Evidence is presented that clonazepam influenced homosynaptic depression of the biceps-semitendinosus pathway by lengthening the primary afferent depolarization (PAD). This prolongation of the primary afferent depolarization did not last for the entire duration of the train as primary afferent depolarization also underwent depression. Therefore later responses in the train were unaffected by clonazepam. Homosynaptic depression of the triceps surae pathway was not similarly affected because activation of triceps surae afferents does not cause significant depolarization of its own afferents. It is suggested that the enhancement of GABAergic transmission at least partially underlies the effect of clonazepam on homosynaptic depression.
Davies
M F
MF
Esplin
B
B
Capek
R
R
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002415:Cats; D002998:Clonazepam / Q000494:pharmacology; D012023:Reflex, Monosynaptic / Q000187:drug effects; D012663:Semicarbazides / Q000494:pharmacology; D013116:Spinal Cord / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D012663:Semicarbazides; C010059:carbamylhydrazine; D005680:gamma-Aminobutyric Acid; D002998:Clonazepam; D001640:Bicuculline