ABSTRACT
OBJECTIVE: Stimulation of the central cholinergic system results in generalized epileptic seizures. The goal of this study was to map the epileptogenic effects of the cholinergic agonist, carbachol injected into different sites of the basal forebrain and diencephalon of the rat brain. METHODS: Carbachol was injected directly into the brain in a dose of 1 or 3 micrograms. Seizures were assessed behaviourally on a five-stage scale with electroencephalographic controls. Seizures at stage 1 were the least severe and those at stage 5 the most severe. RESULTS: Injections of high dose carbachol (3 micrograms) induced seizures from 40% of all injected brain sites. Injections of low dose carbachol (1 microgram) or isotonic saline into the same brain sites did not cause any behavioural or electrographic seizures. The majority of sites (84%) producing generalized seizures (stage 5) were concentrated in or around the zona incerta. CONCLUSIONS: Within the anatomical limits of the study, the zona incerta is the area most sensitive to carbachol-induced generalized seizures.
Subject(s)
Diencephalon/physiopathology , Epilepsy, Generalized/physiopathology , Parasympathetic Nervous System/physiopathology , Animals , Behavior, Animal/drug effects , Carbachol/administration & dosage , Carbachol/pharmacology , Diencephalon/pathology , Electroencephalography/drug effects , Epilepsy, Generalized/chemically induced , Epilepsy, Generalized/pathology , Injections , Male , Parasympathetic Nervous System/pathology , Prosencephalon/pathology , Rats , Rats, WistarABSTRACT
The present study was designed to determine the types of acetylcholine receptors involved in the initiation of epileptic seizures from the zona incerta and surrounding structures by cholinergic stimulation in rats. Unilateral intracerebral microinjection of the mixed muscarinic and nicotinic agonist carbachol (3 micrograms) produced generalized seizures in 12 of 20 rats studied. Local pretreatment with equimolar doses of acetylcholine receptor antagonists was used as a method of determining the receptor type involved in the initiation of cholinergically induced seizures in the rat diencephalon. Pretreatment with the M1 muscarinic receptor antagonist, pirenzepine (7 micrograms), abolished carbachol-induced seizures in 91% of the animals tested. The M2 muscarinic receptor antagonist, methoctramine (12 micrograms) and the nicotinic receptor antagonist, mecamylamine (3 micrograms), were relatively ineffective in antagonizing seizures in 9% and 27%, respectively. The results suggest that M1 muscarinic receptors are preferentially involved in the initiation of generalized epileptic seizures in the basal diencephalon of the rat.
