strychnine and Epilepsy--Absence

Thalamocortical spike-and-wave discharges characterize the nonconvulsive absence seizures that occur spontaneously in genetic absence epilepsy rats from Strasbourg (GAERS), a selected strain of Wistar rats. GABA is crucial in the generation of absence seizures. The susceptibility to convulsions induced by threshold doses of various GABA receptor antagonists and inhibitors of GABA synthesis, kainic acid and strychnine, was compared in GAERS and in nonepileptic rats from a selected control strain (NE). The brain structures involved in the drug-elicited convulsive seizures were mapped by c-Fos immunohistochemistry. Injection of various antagonists of the GABA(A) receptor, bicuculline and picrotoxin, and inverse agonists of the benzodiazepine site (FG 7142 and DMCM) induced myoclonic spike-and-wave discharges followed by clonic or tonic-clonic seizures with high paroxysmal activity on the cortical EEG. The incidence of the convulsions was dose-dependent and was higher in GAERS than in NE rats. Mapping of c-Fos expression showed that the frontoparietal cortex was constantly involved in the convulsive seizures elicited by a threshold convulsant dose, whereas limbic participation was variable. In contrast, GAERS were less susceptible than NE rats to the tonic-clonic convulsions induced by the inhibitors of glutamate decarboxylase, isoniazide and 3-mercaptopropionic acid. The GABA(B) receptor antagonist CGP 56999 and kainic acid induced a similar incidence of seizures in GAERS and NE rats and predominantly activated the hippocampus. No difference in the tonic seizures elicited by strychnine could be evidenced between the strains. These results suggest that an abnormal cortical GABAergic activity may underlie absence seizures in GAERS.

Topics: 3-Mercaptopropionic Acid; Animals; Bicuculline; Carbolines; Convulsants; Electroencephalography; Epilepsy, Absence; Frontal Lobe; GABA Antagonists; GABA-A Receptor Antagonists; gamma-Aminobutyric Acid; Glutamate Decarboxylase; Isoniazid; Kainic Acid; Limbic System; Male; Parietal Lobe; Picrotoxin; Proto-Oncogene Proteins c-fos; Rats; Rats, Mutant Strains; Rats, Wistar; Seizures; Strychnine

gamma-Hydroxybutyric acid (GHB), a naturally occurring compound which is synthesized from gamma-aminobutyric acid (GABA), induces bilaterally synchronous spike wave discharges, associated with behavioral changes, reminiscent of petit mal or generalized absence seizures in rats. In the present study, possible involvement of excitatory amino acids (EAAs) in GHB-induced spike wave discharges was investigated. The noncompetitive antagonist of NMDA receptors, MK-801, attenuated GHB-induced spike wave discharges at all doses tested (0.025-1.0 mg/kg) but dose-dependently induced suppression of EEG bursts in GHB-treated animals. The suppression of bursts was never observed with GHB in control experiments. N-Methyl-D-aspartate (NMDA) had a similar effect on GHB-induced spike wave discharges, when it was administered prior to GHB. This effect of NMDA was partially reversed by MK-801. The competitive antagonists of NMDA receptors, (+/-)CPP and CGP 43487 and the antagonist at the strychnine-insensitive glycine site, HA-966, also suppressed GHB-induced spike wave discharges with the EEG progressing to suppression of bursts but were weaker in this regard than MK-801 or NMDA. These data raise the possibility of involvement of excitatory amino acids in the GHB model of absence seizures.

Topics: Amino Acids; Animals; Dizocilpine Maleate; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy, Absence; Injections, Intraventricular; Male; N-Methylaspartate; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Sodium Oxybate; Strychnine

Topics: Action Potentials; Animals; Behavior, Animal; Bicuculline; Electroencephalography; Epilepsy, Absence; GABA Antagonists; gamma-Aminobutyric Acid; Imidazoles; Male; Muscimol; Photic Stimulation; Picrotoxin; Rats; Strychnine

Topics: Acoustic Stimulation; Animals; Antipsychotic Agents; Brain Mapping; Cats; Caudate Nucleus; Cerebral Cortex; Disease Models, Animal; Electric Stimulation; Electroencephalography; Epilepsy, Absence; Epilepsy, Tonic-Clonic; Hippocampus; Humans; Mesencephalon; Myoclonus; Neural Pathways; Pentylenetetrazole; Phenothiazines; Psychotic Disorders; Reticular Formation; Seizures; Spinal Cord; Strychnine

Topics: Animals; Cats; Cerebral Cortex; Corpus Callosum; Electroencephalography; Epilepsy, Absence; Estrogens, Conjugated (USP); Hypothalamus; Mesencephalon; Pentylenetetrazole; Strychnine; Thalamus