Stimulation of alpha(2)-adrenoceptors delays the development of kindling, a model
of epileptogenesis in humans. Blocking alpha(2)-adrenoceptors is proconvulsant, but
has beneficial effects on somatomotor recovery after experimental stroke. We investigated
whether atipamezole, a selective alpha(2)-adrenoceptor antagonist, affects the recovery
process from status epilepticus (SE)-induced brain damage, which affects the risk
of epileptogenesis. Vehicle or atipamezole (100 microg/kg/h) treatment was started
1 week after the induction of SE and continued for 9 weeks using Alzet minipumps (n
= 70). Development and severity of epilepsy, spatial and emotional learning, and histologic
analysis were used as outcome measures. There were no differences in the percentage
of animals with epilepsy in the different treatment groups. In the atipamezole group,
however, daily seizure frequency was lower (P < 0.01), a higher percentage of epileptic
animals had mild epilepsy (<1 seizure/day; P < 0.01), and seizure frequency did not
increase over time compared with the vehicle group. The atipamezole group had milder
hilar cell damage (P < 0.05) and less intense mossy fiber sprouting (P < 0.05). Behavioral
impairments were similar between groups. Our data indicate that chronic treatment
with atipamezole does not prevent epileptogenesis. There is, however, a disease-modifying
effect; that is, the epilepsy that develops is milder and non-progressive. These data
warrant further studies.