Facilitation of amygdala kindling after norepinephrine depletion with 6-hydroxydopamine in rats

Abstract

It is unclear whether rats pretreated with desmethylimipramine (DMI) and 6-hydroxydopamine (6-OH) kindled at a rate similar to controls because the DMI protected the brain norepinephrine (NE) from 6-OH, or whether it was because DMI exhibited a long-term antiepileptic effect, independent of NE protection, which counteracted the facilitative action on kindling of 6-OH alone. Rats with bipolar amygdala electrodes were pretreated bilaterally with intraventricular 6-OH and/or subcutaneous DMI to deplete brain NE and/or dopamine (DA). All rats were subsequently subjected to daily low-intensity electrical stimulation of the amygdala which resulted in the development of clonic motor seizures (kindling). With injections of 6-OH alone or DMI 1 week before or 2 weeks after 6-OH, extensive depletion of NE occurred, paralleled by very rapid kindling. Importantly, the form and duration of these convulsions was the same as for all other groups. DMI administered 30 min before 6-OH (30-min-6-OH group) substantially protected the NE but not the DA fibers and resulted in kindling similar to the saline- or DMI-injected control rats. Unlike our previous observation, DMI alone did not retard the spread of afterdischarge. Collectively these data confirm the importance of NE in amygdala kindling, and indicate that the normalcy in kindling of the 30-min-6-OH group was related to the protection of their NE by DMI and not to a long-term antiepileptic action of DMI.