examined sensitivity to the acetylcholin-
esterase inhibitor aldicarb. Aldicarb causes
paralysis of body movement resulting from
the accumulation of acetylcholine at the
neuromuscular junction (
). Mutations that
reduce synaptic transmission cause resistance
to aldicarb (
). In contrast, mutations that
stimulate synaptic transmission cause hyper-
sensitivity to aldicarb-mediated paralysis (
Trimethadione treatment of wild-type animals
caused hypersensitivity to aldicarb-mediated
paralysis (Fig. 3E). The control drug, succin-
imide, did not cause hyperactive motility or
aldicarb hypersensitivity (
). These results
indicate the anticonvulsants stimulate synaptic
transmission in the neuromuscular system that
controls body movement.
Ethosuximide and trimethadione effec-
tively treat absence seizures in humans by
regulating neural activity. A likely target of
ethosuximide is T-type calcium channels,
although it is possible that these compounds
act on multiple targets (
). These anti-
convulsants also affected neural activity in
nematodes, and the anticonvulsant and the
life-span extension effects of the compounds
may act through similar mechanisms. The
findings presented here are consistent with
the model that the effect on neural activity
causes the life-span extension, although they
do not exclude the possibility that the drugs
affect neural activity and aging by different
mechanisms. Furthermore, the interactions
with the insulin-signaling mutants suggest
the intriguing possibility that neural activity
regulates aging by both
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