Oral and intraperitoneal administration of the
nucleoside guanosine have been shown to prevent
quinolinic acid- (QA) and
alpha-dendrotoxin-induced
seizures, impair memory, and impair anxiety in rats and mice. We investigated the effect of 2-weeks ad lib orally administered
guanosine (0.5 mg/ml) on
seizures induced by QA, inhibitory avoidance memory, and locomotor performance in rats. We also studied the mechanism of action of
guanosine through the measurement of its concentration in the cerebrospinal fluid (CSF) and its effect on
glutamate uptake in cortical slices of rats. QA produced
seizures in 85% of rats, an effect partially prevented by
guanosine (53% of
seizures; P = 0.0208).
Guanosine also impaired retention on the inhibitory avoidance task (P = 0.0278) and decreased locomotor activity on the open field test (P = 0.0101). The CSF
guanosine concentration increased twofold in the treated group compared to that in the vehicle group (P = 0.0178). Additionally, QA promoted a 30% decrease in
glutamate uptake as compared to that with intracerebroventricular saline administration, an effect prevented by
guanosine in animals protected against QA-induced
seizures. Altogether, these findings suggest a potential role of
guanosine for treating diseases involving glutamatergic excitotoxicity such as
epilepsy. These effects seem to be related to modulation of
glutamate uptake.