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

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

European Journal of Pharmacology 138(3): 309-318

ISSN/ISBN: 0014-2999

PMID: 3040437

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.

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Accession: 040819961

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