Effect of clonidine on amygdala kindling in normal and 6-hydroxydopamine-pretreated rats

The role of the alpha 2 adrenergic receptor in the development and propagation of amygdala kindled seizures was determined. Male Wistar rats, depleted of norepinephrine with the neurotoxin 6-hydroxydopamine and vehicle controls, received an injection of the alpha 2 agonist, clonidine (0.001, 0.01, or 0.1 mg/kg, i.p.), or saline, 30 min prior to each amygdala stimulation (every 3 to 4 days). The largest dose of clonidine had a significant retarding effect on the development of kindling in both the vehicle- and 6-hydroxydopamine-treated groups. The majority of this effect was observed as a protracted number of trials with unilateral afterdischarge. When the discharge became bilateral, generalized seizures were soon apparent. There was no effect of clonidine on the amygdala afterdischarge threshold in both groups, or on the subsequent generalized motor seizure and associated afterdischarge durations in the vehicle groups. The largest dose of clonidine, however, reduced the severity of the convulsive response in the 6-hydroxydopamine-treated rats from violent stage 7 or 8 seizures to more moderate stage 5 responses. The significance of these data, and the involvement of the postsynaptic alpha 2 receptors in the genesis of amygdala kindled seizures, are discussed.