The role of the alpha-2 adrenergic receptor in the development and expression of kindled seizures was examined in vivo . Male Wistar rats were pretreated with either vehicle (VEH) or the neurotoxin 6-hydroxydopamine (6-OHDA). Subsequently all rats were given an acute injection of one of the three clonidine doses (0.001, 0.01, 0.1 mg/kg), an alpha-2 agonist, or saline 30 minutes prior to each kindling trial.
The 6-OHDA pretreatment facilitated the rate of kindling and was associated with stronger than normal seizures. Clonidine (0.1 mg/kg), on the other hand, had an anticonvulsant effect on the development of kindling in both the VEH and 6-OHDA pretreated rats and attenuated the strength of the motor response in the latter group. These antiepileptic effects of clonidine, in the 6-OHDA rats suggests that many alpha-2 receptors reside postsynaptically.
These results suggest an important inhibitory role of the alpha-2 adrenergic receptors in the development of kindled seizures.