Kindling: a pharmacological approach.
Injection of a few nanomoles of the muscarinic agonists carbamylcholine, muscarine or (+)-acetyl-beta-methylcholine once a day into the rat amygdala was initially subconvulsive, but on repetition led to the progressive development of kindled epileptic seizures. This behaviour was stereospecific, was potentiated by the cholinesterase inhibitor physostigmine, and was blocked by the muscarinic antagonists atropine, QNB and scopolamine. The kindling potencies of cholinergic muscarinic agonists and antagonists paralleled their relative affinities for muscarinic receptors in vitro. No changes in muscarinic receptors, in cholinesterase or in choline acetyltransferase were observed in kindled brains after a stimulation-free period of at least 1 week. These data support the aggregate hypothesis of epileptogenesis and suggest that abnormal activity through a particular group of muscarinic synapses can be sufficient to generate an epileptic focus.
D000679:Amygdala / Q000502:physiology; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D011976:Receptors, Muscarinic; D001285:Atropine; D002217:Carbachol; D002795:Choline O-Acetyltransferase