REGIONAL FOREBRAIN NORADRENALINE RELEASE IN RESPONSE TO FOCAL AND GENERALIZED SEIZURES INDUCED BY HIPPOCAMPAL KINDLING STIMULATION

In vivo microdialysis is was used to monitor noradrenalin (NA) release in the rat hippocampus, sensorimotor cortex and amygdala in response to seizures induced by electrical kindling stimulation in the hippocampus. Generalized seizures increased NA output in the hippocampus five-fold above baseline level (as assessed with 2-min sampling periods). The peak value was seen 2-4 min after onset of seizure activity and baseline was reached after another 6-8 min. In the sensorimotor cortex, there was a seven-fold increase showing a similar time-course. Focal hippocampal seizures gave rise to threefold and 80% increases above baseline in the hippocampus and sensorimotor cortex, respectively. A unilateral knife transection of the dorsal noradrenergic bundle reduced hippocampal NA release induced by focal seizures by 53%. In animals subjected to 30 stimulus-evoked seizures with 5-min intervals ('rapid kindling'), maximal NA output was observed after the third seizure in both hippocampus (237% increase) and amygdala (122% increase). NA levels tapered off with repeated stimulation and reached baseline after nine stimulations in the hippocampus; in the amygdala, the NA output was still slightly elevated at the end of the stimulation period. These results indicate that there is a general activation of the locus coeruleus system during focal as well as generalized seizures, as evidenced by marked increases in transmitter release from noradrenergic terminals in all forebrain areas studied. NA output in areas exhibiting seizure activity is dependent on impulse flow in locus coeruleus neurons and probably also on local regulatory mechanisms active at the noradrenergic terminal level. The increase in inhibitory noradrenergic transmission in both epileptic and non-epileptic brain regions may dampen ongoing seizure activity as well as lessen its spread and generalization.