The repeated administration of the
beta-carboline,
FG 7142, to mice leads to 'chemical kindling', i.e., the development of
seizures following doses which were initially insufficient to produce convulsive activity.
Messenger RNA (
mRNA) was prepared from the cortex of control and FG 7142-treated mice killed
at 10-12 days or at 28-45 days after the last kindling injection, and this
mRNA was injected into Xenopus oocytes. At 3-4 days following injection, a voltage clamp technique was used to record responses to
kainic acid,
gamma-aminobutyric acid (
GABA), and
N-methyl-D-aspartate (
NMDA).
Kainate was significantly more potent in oocytes expressing
mRNA from kindled mice killed at either 10-12 or 28-45 days than in those injected with control
mRNA.
GABA also was more potent in oocytes with
mRNA from kindled mice killed
at 10-12 days, but this difference was not present at the longer interval. Chemical kindling did not change the response to
NMDA. The current-voltage relation for
kainate responses was linear, and plots from kindled and control
mRNA were similar. The persistent increase in potency of
kainate, an excitatory
glutamate ligand, may play a role in producing the lowered
FG 7142 threshold characteristic of kindled mice.