Norepinephrine modulates seizures induced by quinolinic acid in rats: selective and distinct roles of α-adrenoceptor subtypes

We investigated in rats whether alterations in noradrenergic function caused by 6-hydroxydopamine or α- and β-adrenoceptor agonists and antagonists would modify the susceptibility of the brain to electroencephalographic seizures induced by intrahippocampal infusion of quinolinic acid. 6-Hydroxydopamine depletion of norepinephrine facilitated the expression of seizures while α-adrenoceptor stimulation by clonidine had either proconvulsant (0.1 mg/kg) or anticonvulsant (from 0.5 to 2 mg/kg) effects. Clonidine's anticonvulsant activity (0.5 mg/kg) was mimicked by methoxamine given intrahippocampally (10 μg), and antagonized by prazosin (1 mg/kg), whereas both yohimbine (5 and 10 mg/kg) and piperoxane (5 mg/kg) had no significant effect. Seizure facilitation induced by clonidine (0.1 mg/kg) was blocked by yohimbine (10 mg/kg). Systemic (0.25 and 0.5 mg/kg) or intrahippocampal (10 and 20 μg) isoproterenol and propranolol (10 mg/kg) had no effect. Spiking activity and neurotoxicity induced by quinolinic acid were unaltered by treatments which protected against convulsions. Modulation of quinolinic acid-convulsive activity by α-adrenoceptor subtypes appears to be selective and complex, since α 1-type activation reduces seizures while α 2-type stimulation has proconvulsant effects.