Is amygdala kindling in rats a model for drug-resistant partial epilepsy? 1986

W Löscher, and R Jäckel, and S J Czuczwar

Amygdala-kindled female rats were used to compare the effects of seven antiepileptic drugs that are clinically used for treatment of partial epilepsy with complex symptomatology, on generalized seizures, focal seizures, or electrographic seizure activity at the focus. As a second approach of drug evaluation, drug effects on mean latency, severity, and duration of the seizures were determined. Anticonvulsant potencies obtained were compared with those determined in the maximal electroshock seizure test in female rats. Phenobarbital, phenytoin, carbamazepine, valproic acid, diazepam, clonazepam, but not primidone dose-dependently suppressed generalized motor seizures in kindled rats; however, except for the benzodiazepines, ED50S were substantially higher than those determined in the maximal electroshock seizure test. Compared with their effect on generalized motor seizures, all drugs were much less potent in blocking focal seizures and afterdischarges recorded from the amygdala. The data suggest that with respect to behavioral and pharmacologic characteristics of the amygdala kindling model, fully kindled rats may be a useful model for drug-resistant complex partial seizures with secondary generalization. Results of experiments with novel inhibitors of GABA uptake, which were inactive in the maximal electroshock seizure test but highly potent against kindled seizures, suggest that such drugs might be more effective than current antiepileptic drugs for treatment of partial epilepsy.

UI MeSH Term Description Entries
D007696 Kindling, Neurologic The repeated weak excitation of brain structures, that progressively increases sensitivity to the same stimulation. Over time, this can lower the threshold required to trigger seizures. Kindlings, Neurologic,Neurologic Kindling,Neurologic Kindlings
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D004828 Epilepsies, Partial Conditions characterized by recurrent paroxysmal neuronal discharges which arise from a focal region of the brain. Partial seizures are divided into simple and complex, depending on whether consciousness is unaltered (simple partial seizure) or disturbed (complex partial seizure). Both types may feature a wide variety of motor, sensory, and autonomic symptoms. Partial seizures may be classified by associated clinical features or anatomic location of the seizure focus. A secondary generalized seizure refers to a partial seizure that spreads to involve the brain diffusely. (From Adams et al., Principles of Neurology, 6th ed, pp317) Abdominal Epilepsy,Digestive Epilepsy,Epilepsy, Focal,Epilepsy, Simple Partial,Focal Seizure Disorder,Gelastic Epilepsy,Partial Epilepsy,Partial Seizure Disorder,Seizure Disorder, Partial,Simple Partial Seizures,Amygdalo-Hippocampal Epilepsy,Benign Focal Epilepsy, Childhood,Benign Occipital Epilepsy,Benign Occipital Epilepsy, Childhood,Childhood Benign Focal Epilepsy,Childhood Benign Occipital Epilepsy,Epilepsy, Benign Occipital,Epilepsy, Localization-Related,Epilepsy, Partial,Occipital Lobe Epilepsy,Panayiotopoulos Syndrome,Partial Seizures, Simple, Consciousness Preserved,Rhinencephalic Epilepsy,Seizure Disorder, Focal,Subclinical Seizure,Uncinate Seizures,Abdominal Epilepsies,Amygdalo-Hippocampal Epilepsies,Benign Occipital Epilepsies,Digestive Epilepsies,Disorders, Focal Seizure,Disorders, Partial Seizure,Epilepsies, Abdominal,Epilepsies, Amygdalo-Hippocampal,Epilepsies, Benign Occipital,Epilepsies, Digestive,Epilepsies, Focal,Epilepsies, Gelastic,Epilepsies, Localization-Related,Epilepsies, Occipital Lobe,Epilepsies, Rhinencephalic,Epilepsies, Simple Partial,Epilepsy, Abdominal,Focal Epilepsies,Focal Epilepsy,Focal Seizure Disorders,Gelastic Epilepsies,Lobe Epilepsy, Occipital,Localization-Related Epilepsies,Localization-Related Epilepsy,Occipital Epilepsies, Benign,Occipital Epilepsy, Benign,Occipital Lobe Epilepsies,Partial Epilepsies,Partial Epilepsies, Simple,Partial Seizure Disorders,Partial Seizures, Simple,Rhinencephalic Epilepsies,Seizure Disorders, Focal,Seizure Disorders, Partial,Seizure, Subclinical,Seizure, Uncinate,Seizures, Simple Partial,Seizures, Subclinical,Seizures, Uncinate,Simple Partial Epilepsies,Subclinical Seizures,Uncinate Seizure
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000927 Anticonvulsants Drugs used to prevent SEIZURES or reduce their severity. Anticonvulsant,Anticonvulsant Drug,Anticonvulsive Agent,Anticonvulsive Drug,Antiepileptic,Antiepileptic Agent,Antiepileptic Agents,Antiepileptic Drug,Anticonvulsant Drugs,Anticonvulsive Agents,Anticonvulsive Drugs,Antiepileptic Drugs,Antiepileptics,Agent, Anticonvulsive,Agent, Antiepileptic,Agents, Anticonvulsive,Agents, Antiepileptic,Drug, Anticonvulsant,Drug, Anticonvulsive,Drug, Antiepileptic,Drugs, Anticonvulsant,Drugs, Anticonvulsive,Drugs, Antiepileptic
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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