The Basal Ganglia, the Deep Prepyriform Cortex, and Seizure Spread: Bicuculline is Anticonvulsant in the Rat Striatum

• Published in: Proceedings of the National Academy of Sciences - PNAS 1989-03, Vol.86 (5), p.1694-1697
• Main Authors: Turski, Lechoslaw, Cavalheiro, Esper A., Calderazzo-Filho, Lineu S., Bortolotto, Zuner A., Klockgether, Thomas, Ikonomidou, Chrysanthy, Turski, Waldemar A.
• Format: Article
• Language: English
• Subjects: Animals; Anticonvulsants; Basal Ganglia - drug effects; Basal Ganglia - physiology; Basal Ganglia - physiopathology; Bicuculline - analogs & derivatives; Bicuculline - pharmacology; Biological and medical sciences; Body mass index; Brain - drug effects; Brain - physiology; Brain - physiopathology; Central nervous system; Convulsants; Convulsions; Corpus Striatum - drug effects; Corpus Striatum - physiology; Corpus Striatum - physiopathology; Dosage; Electrophysiology; Epilepsy; Fundamental and applied biological sciences. Psychology; Hippocampus; Male; Microinjections; Rats; Rats, Inbred Strains; Reference Values; Seizures; Seizures - physiopathology; Vertebrates: nervous system and sense organs
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.5.1694

The γ -aminobutyric acid antagonist, bicuculline methiodide (BMI), induces myoclonic seizures in rats when injected into the deep prepyriform cortex at concentrations lower than those that induce convulsions from the amygdala, hippocampus, or neocortex. This observation prompted the suggestion that the deep prepyriform cortex was responsible for seizure generation regardless of the neurotransmitter and neuronal circuits involved. Bilateral intrastriatal application of BMI protects rats against seizures induced by (i) local application of BMI into the deep prepyriform cortex and (ii) systemic application of bicuculline, pilocarpine (a cholinergic agonist), or kainic acid (a glutamate receptor agonist). The region of the striatum sensitive to the previously unknown anticonvulsant action of BMI is located in the immediate vicinity of the deep prepyriform cortex and is 100-150 times more sensitive to the anticonvulsant action relative to the sensitivity of the deep prepyriform cortex to the convulsant action of BMI. These data suggest a powerful γ -aminobutyric acid-dependent gating role of the basal ganglia in determining the seizure threshold in the forebrain. This argues against the suggestion that the deep prepyriform cortex plays a crucial role in the generation of seizures following systemic administration of convulsants. The discovery of an anticonvulsant action of BMI in the rat striatum contradicts the γ -aminobutyric acid theory of epilepsy, which implies that deficits in the γ -aminobutyric acid-mediated inhibition in the central nervous system lead to the emergence of seizures.