Chemical kindling by muscarinic amygdaloid stimulation in the rat.
507 Holtzman rats received injections, through chemitrodes chronically implanted into the basolateral amygdala, of 0.2-1 microliter of sterile isotonic solution containing nanomolar quantities of cholinergic muscarinic agonists and/or antagonists. The bulk of the injected solution diffused only a short distance as judged by autoradiography. Once daily injections of 2.7 nmoles of carbamylcholine, an initially subconvulsive dose, kindled the progressive development of epileptic seizures similar to those seen in electrical amygdaloid kindling. This response was dependent on dose and on interstimulus interval, and once established persisted at least 8 weeks without further stimulation. Spontaneous seizures were observed in some fully kindled animals. No kindling-specific changes were seen by light microscopy. Muscarine (3 nmol) and the active (+), but not the inactive (-), isomer of acetyl-beta-methylcholine also kindled seizures. The action of (+)-acetyl-beta-methylcholine was potentiated by the cholinesterase inhibitor physostigmine. The muscarinic antagonists atropine and quinuclidinyl benzylate (QNB) blocked kindling by carbamylcholine or muscarine. Atropine, QBN and scopolamine greatly reduced agonist-induced seizures in previously kindled rats. Highly significant transfer effects were observed between muscarinic agonists, i.e. muscarine-kindled rats had widespread seizures on their first carbamylcholine exposure and vice versa. Kindled animals had a lowered seizure threshold for muscarinic agonists. Dibutyryl cyclic GMP produced seizures but no kindling. Those results demonstrate that in this model the stimulation of a group of muscarinic cholinergic synapses is both necessary and sufficient to induce a kindled state characterized by both evoked and spontaneous seizures, and support the view that epilepsy can be acquired and expressed transsynaptically.
D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D007696:Kindling, Neurologic / Q000187:drug effects*; D009115:Muridae; D009116:Muscarine / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects
D011976:Receptors, Muscarinic; D003995:Dibutyryl Cyclic GMP; D011813:Quinuclidinyl Benzilate; D001285:Atropine; D009116:Muscarine; D002217:Carbachol; D010830:Physostigmine