Infusions of an excitant
amino acid,
N-methyl-D-aspartate (
NMDA) into the inferior colliculus (IC) render normal rats susceptible to audiogenic
seizures (AGS) and/or spontaneous audiogenic-like
seizures without tonic components. The excess excitant
amino acid in the IC and the
anticonvulsant effects of
NMDA antagonists in genetically
epilepsy-prone rats (GEPRs), along with innate
norepinephrine (NE) deficits and
anticonvulsant effects of NE agonists in these animals suggest a mutual role of excitant
amino acids and NE in regulating AGS in GEPRs. Saline or
6-hydroxydopamine (6-OHDA, 4 micrograms/side in 2 microliters) was infused bilaterally into the locus coeruleus (LC) of normal male rats and guide cannulas were implanted into the IC. Two weeks later,
NMDA was infused bilaterally into the IC (0.5 microliters; 10 nmol/side) and 10 min later the rats were subjected to an electric bell (110
db, 60 s) unless preceded by spontaneous
tonic seizures.
Tonic seizures were not observed in male rats following
NMDA infusions in rats with LC infusions of saline. However, a marked increase in the incidence of
tonic seizures was observed in the 6-OHDA-treated rats which were markedly depleted of brain NE as determined by HPLC. These findings indicate that a NE deficit greatly enhances the incidence of tonic convulsions and support the hypothesis that an excitant
amino acid excess in the GEPR IC may act to initiate AGS, whereas the NE deficit may allow expression of the tonic components of AGS seen in some GEPRs.