Guanosine and GMP prevent seizures induced by quinolinic acid in mice

In the mammalian CNS, glutamate and GABA are the principal neurotransmitter s mediating excitatory and inhibitory synaptic events. respectively, and ha ve been implicated in the neurobiology of seizures. Guanine-based purines, including the nucleoside guanosine and the nucleotide GMP, have been shown to antagonize glutamatergic activity at the receptor level and the other pu rine nucleoside adenosine is a well-known modulator of seizure threshold. L n the present study we investigated the anticonvulsant effect of i.p. guano sine and GMP against seizures induced by the glutamate agonist quinolinic a cid (QA) or the GABA, antagonist picrotoxin in mice. Animals were pretreate d with an i.p, injection of saline, guanosine or GMP 30 min before either a n i.c.v. injection of 4 mu l QA (36.8 nmol) or a subcutaneous injection of picrotoxin (3.2 mg/kg). All animals pretreated with vehicle followed by QA or picrotoxin presented seizures, which were completely prevented by the NM DA antagonist MK-801 and the GABA agonist phenobarbital, respectively. Guan osine and GMP dose-dependently protected against QA-induced seizures, up to 70 and 80% at 7.5 mg/kg, with ED50=2.6+/-0.4 and 1.7+/-0.6 mg/kg. respecti vely. Conversely, neither guanosine, GMP nor MK-801 affected picrotoxin-ind uced seizures, indicating some degree of specificity towards the glutamater gic system. This study suggests anticonvulsant properties of i.p. guanosine and GMP, which may be related with antagonism of glutamate receptors. (C) 2000 Elsevier Science B.V. All rights reserved.