Kindling antagonism: a role for hindbrain norepinephrine in the development of site suppression following concurrent,...

The concurrent, alternate electrical stimulation of the septal nucleus and the entorhinal cortex results in the development of fully generalized seizures at one site (dominant site) and the lack of development of kindled seizures at the other (suppressed or antagonized site). We have labeled this phenomenon kindling antagonism. Previous work from our laboratory has demonstrated that the whole brain depletion of norepinephrine (NE) eliminates the development of kindling antagonism. In the present study animals were treated with the neurotoxin 6-hydroxydopamine (6-OHDA) as neonates. The neonatal administration of 6-OHDA produced robust increases in brainstem and cerebellar NE levels and depletions of forebrain NE levels when assayed at maturity. Striatal dopamine levels were spared by this treatment. Neonatal 6-OHDA did not alter the development of the kindling antagonism phenomenon which is typically observed following concurrent, alternate stimulation of the septal nucleus and entorhinal cortex. Neonatal 6-OHDA treatment significantly facilitated the rate of kindled seizure development at dominant sites but failed to alter thresholds for the elicitation of afterdischarges (AD) or patterns of development of AD durations. Other characteristics of kindling antagonism were similarly unaffected by 6-OHDA treatment. These data suggest that brainstem and/or cerebellar NE are sufficient to mediate the development of kindling antagonism in the relative absence of forebrain NE.