Modulation of audiogenically kindled seizures by gamma-aminobutyric acid-related mechanisms in the amygdala.
Repetitive induction of audiogenic seizures (AGSs) ("AGS kindling") results in expansion of the AGS neuronal network from the brainstem to forebrain structures. AGSs in kindled genetically epilepsy-prone rats (GEPR-9s) exhibit a significant increase in the duration of posttonic clonus (PTC). The amygdala (AMG) does not appear to be a required network component before AGS kindling, but this structure is implicated in the seizure network after AGS kindling. gamma-Aminobutyric acid (GABA) is a major neurotransmitter in AMG, and histamine receptor activation is also reported to stimulate GABA release. The present study examined the effect on audiogenically kindled seizures of focal microinjections into the AMG of GEPR-9s. AGS kindling involved induction of 14 AGSs in GEPR-9s. Bilateral microinjection of a GABA(A) agonist, muscimol (0.3 nmol/side), into the AMG significantly reduced the duration of PTC, starting 0.5 h after drug infusion, with recovery by 24 h. Microinjection of histamine (60 nmol/side) suppressed PTC at 0.5 h, with total blockade at 24 h, but the seizure pattern did not revert to that observed before kindling until 120 h. This long duration suggests that mechanisms in addition to modulation of GABA function may be involved in the effect of histamine. The wild running and tonic components of AGS were never affected by microinjection of these agents into the AMG. These findings confirm previous work suggesting that the AMG is not a required nucleus in the AGS neuronal network before kindling. However, the AMG becomes critical in expansion of the seizure network during AGS kindling, and audiogenically kindled seizures are negatively modulated by increased GABA function.
Feng
H J
HJ
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois 62794, USA.
Naritoku
D K
DK
Randall
M E
ME
Faingold
C L
CL
D000161:Acoustic Stimulation; D000679:Amygdala / Q000503:physiopathology*; D000818:Animals; D004827:Epilepsy / Q000235:genetics / Q000503:physiopathology*; D018755:GABA Agonists / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D006632:Histamine / Q000494:pharmacology; D007696:Kindling, Neurologic; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011922:Rats, Mutant Strains / Q000235:genetics; D011963:Receptors, GABA-A / Q000502:physiology; D011968:Receptors, Histamine / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018755:GABA Agonists; D011963:Receptors, GABA-A; D011968:Receptors, Histamine; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D006632:Histamine