Cortical-area specific block of genetically determined absence seizures by ethosuximide.
Absence epilepsy is characterised by a paroxysmal loss of consciousness, of abrupt onset and termination, and is associated with a bilateral synchronous spike and wave discharge (SWD) on the electroencephalogram. Absence seizures involve an interplay between thalamic and cortical structures, although most research has so far focussed on sensory thalamic nuclei and the reticular thalamic nucleus (RTN). Thus, microinfusion of ethosuximide (ETX), a first choice anti-absence drug, into either the ventrobasal thalamus or RTN of the genetic absence epilepsy rat from Strasbourg (GAERS), a validated rat model of absence epilepsy, does not produce immediate cessation of seizure activity, as is seen following systemic administration. As recent evidence indicates a seizure initiation site within the peri-oral region of the primary somatosensory cortex (S1po), we have now applied ETX into S1po as well as the somatosensory cortex forelimb region (S1FL) and the motor cortex (M1) of freely moving GAERS. Microinfusion of 10 or 20 nmol/side of ETX into S1po produced an immediate cessation of seizure activity. A less marked response was produced when even a higher dose (200 nmol/side) was infused into S1FL. No reduction of SWD was seen when ETX was infused into M1. Microinfusion of CGP 36742 (5 nmol/side), a GABA(B) antagonist, produced immediate cessation of seizure activity in both S1po and M1 and a delayed effect in S1FL. These data suggest that the ability of ETX to abolish genetically determined absence seizures is cortical-area specific and support the involvement of S1po in the initiation of SWDs.
Manning
J P A
JP
Department of Pharmacology, The Medical School, University of Birmingham, B15 2TT, Birmingham, UK. jpm728@bham.ac.uk
Richards
D A
DA
Leresche
N
N
Crunelli
V
V
Bowery
N G
NG
D000818:Animals; D004832:Epilepsy, Absence / Q000188:drug therapy* / Q000235:genetics*; D005013:Ethosuximide / Q000494:pharmacology / Q000627:therapeutic use*; D009044:Motor Cortex / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013003:Somatosensory Cortex / Q000187:drug effects* / Q000502:physiology
D005013:Ethosuximide