title: Intracerebroventricular administration of inosine is anticonvulsant against quinolinic acid-induced seizures in mice: an effect independent of benzodiazepine and adenosine receptors.
abstract: Inosine (INO) has an anticonvulsant effect against seizures induced by antagonists of GABAergic system. Quinolinic acid (QA) is an agonist NMDA receptors implicated in the neurobiology of seizures. In the present study, we investigated the anticonvulsant effect of intracerebroventricular (i.c.v.) INO administration against QA-induced seizures in adult mice. We also investigated whether the benzodiazepines (BZ) or adenosine (ADO) receptors were involved in the INO effects. Animals were pretreated with an i.c.v. injection of either vehicle or INO before an i.c.v. administration of 4 μl QA (36.8 nmol). All animals pretreated with vehicle followed by QA presented seizures. INO protected against QA-induced seizures in a time and dose dependent manner (up to 60% at 400 nmol, 5 min before QA injection). Diazepam (DZ) and ADO (i.c.v.) also exhibited anticonvulsant effect against QA induced seizures. Additionally, i.p. administration of either flumazenil, a BZ receptor antagonist, or caffeine, an ADO receptor antagonist, did not change the anticonvulsant potency of INO i.c.v. injection, but completely abolished the DZ and ADO anticonvulsant effects, respectively. In conclusion, this study demonstrated that INO exert anticonvulsant effect against hyperactivity of the glutamatergic system independently of BZ or ADO receptors activation.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. ganzellam@hotmail.com
authors.forename: Marcelo
authors.initials: M
authors.lastname: Ganzella
authors.forename: Rafael Berger
authors.initials: RB
authors.lastname: Faraco
authors.forename: Roberto Farina
authors.initials: RF
authors.lastname: Almeida
authors.forename: Vinícius Fornari
authors.initials: VF
authors.lastname: Fernandes
authors.forename: Diogo Onofre
authors.initials: DO
authors.lastname: Souza
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000494:pharmacology; D007276:Injections, Intraventricular; D007288:Inosine / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D051379:Mice; D017378:Quinolinic Acid / Q000633:toxicity*; D011963:Receptors, GABA-A / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants; D011963:Receptors, GABA-A; D018047:Receptors, Purinergic P1; D007288:Inosine; D017378:Quinolinic Acid