Alpha-2 receptors mediate an endogenous noradrenergic suppression of kindling development.
We sought to elucidate the receptor subtype through which endogenous norepinephrine suppresses epileptogenesis in the rat kindling model. To this end we examined the effects of systemically administered selective antagonists and an alpha-2 agonist on kindling development and on kindled seizures. The alpha-2 adrenergic antagonists idazoxan, yohimbine and rauwolscine (0.1-10.0 mg/kg i.p.) dose-dependently facilitated amygdala kindling development. Central administration of idazoxan (20 micrograms/40 microliter i.c.v.) produced an equivalent facilitation. The facilitation was selective for alpha-2 antagonists because neither the alpha-1 antagonist corynanthine (0.1-10.0 mg/kg i.p.), nor the beta antagonist propranolol (0.1-10.0 mg/kg i.p.), nor the selective beta-1 antagonist ICI 89,406 (10 micrograms/40 microliter i.c.v.) nor the beta-2 antagonist ICI 118,551 (0.5-5.0 mg/kg i.p.) modified kindling development. The alpha-2 agonist clonidine (0.01-0.2 mg/kg i.p.) dose-dependently suppressed kindling development. In contrast to the effects on kindling development, neither the alpha-2 antagonists nor clonidine modified seizures elicited from previously kindled animals. We interpret the data to indicate that endogenous norepinephrine suppresses kindling development by activation of postsynaptic alpha-2 receptors. The selective inhibition of kindling development, but not kindled seizures, suggests that alpha-2 agonists may be effective antiepileptogenic, but not anticonvulsant, agents.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D019329:Idazoxan; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D003000:Clonidine; D009638:Norepinephrine; D019329:Idazoxan