Effects of chronic administered guanosine on behavioral parameters and brain glutamate uptake in rats.
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.
Vinadé
Elsa R
ER
Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Avenida Ramiro Barcelos, 2600-Anexo, CEP 90035-003 Porto Alegre, RS, Brazil.
Schmidt
André P
AP
Frizzo
Marcos E S
ME
Portela
Luis V
LV
Soares
Félix A
FA
Schwalm
Fábio D
FD
Elisabetsky
Elaine
E
Izquierdo
Ivan
I
Souza
Diogo O
DO
D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D006151:Guanosine / Q000008:administration & dosage* / Q000633:toxicity; D007266:Inhibition, Psychological; D008297:Male; D017378:Quinolinic Acid / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000134:cerebrospinal fluid / Q000139:chemically induced*
D006151:Guanosine; D018698:Glutamic Acid; D017378:Quinolinic Acid