Norepinephrine modulates seizures induced by quinolinic acid in rats: selective and distinct roles of alpha-adrenoceptor subtypes.
We investigated in rats whether alterations in noradrenergic function caused by 6-hydroxydopamine or alpha- and beta-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 alpha-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 micrograms), 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 micrograms) 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 alpha-adrenoceptor subtypes appears to be selective and complex, since alpha 1-type activation reduces seizures while alpha 2-type stimulation has proconvulsant effects.
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D016627:Oxidopamine; D011725:Pyridines / Q000494:pharmacology*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D012640:Seizures / Q000139:chemically induced*
D006892:Hydroxydopamines; D011725:Pyridines; D011805:Quinolinic Acids; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D016627:Oxidopamine; D017378:Quinolinic Acid; D008729:Methoxamine; D003000:Clonidine; D009638:Norepinephrine