MAO(A) knockout mice are more susceptible to seizures but show reduced epileptogenesis

The role of elevated neuroactive amine exposure during embryonic and early postnatal development on seizure threshold and epileptogenesis was examined using both electrical and pentylenetetrazol (PTZ) kindling in monoamine oxidase A knockout (MAO(A) KO) mice and their wildtype, parental strain (C3H). In the first experiment permanent bilateral electrodes were implanted in the amygdala of both C3H and MAO(A) KO mice. The mice had their afterdischarge threshold determined and then seizures were kindled daily for a total of 20 days. We observed that the MAO(A) KO mice had lower afterdischarge thresholds and less severe seizures compared to the C3H mice. In the second experiment, seizures were elicited in experimentally naive mice using 50mg/kg of PTZ once daily for 7 days. We observed that the MAO(A) KO mice had shorter latencies to the onset of the first seizure, shorter total duration of seizures and fewer seizures per day. Overall the results of both experiments suggest that MAO(A) KO mice have an increased susceptibility to seizures, but are more resistant to epileptogenesis. We conclude that the high levels of neuroactive amines in the MAO(A) KO mice reorganize the brain to make the mice more susceptible to seizures but the remaining high levels of serotonin and norepinephrine likely inhibit epileptogenesis.