Chronically administered guanosine is anticonvulsant, amnesic and anxiolytic in mice.
Acute administration of intraperitoneal and oral guanosine has been shown to prevent quinolinic acid and alpha-dendrotoxin-induced seizures in rats and mice. In this study, we investigated the effects of 2 weeks ad libitum consumption of guanosine (0.5 mg/ml) added to mice water supply on seizures and lethality induced by the alpha-dendrotoxin, hole-board behavior, inhibitory avoidance task, locomotor activity, motor coordination, rectal temperature, body weight, and water and food consumption. Guanosine prevented seizures in 40% and death in 50% on mice treated with i.c.v. alpha-dendrotoxin; it also impaired inhibitory avoidance memory and increased head-dipping behavior and locomotor activity on the hole-board test. Guanosine consumption did not alter any of the other parameters evaluated. The anticonvulsant, amnesic, and anxyolytic-like effects may be associated with the ability of guanosine in modulating the glutamatergic excitatory system. Adding to previously reported data, these findings suggest a potential role for chronic guanosine in the management of diseases associated with glutamatergic excitotoxicity, including epilepsy and anxiety.
Vinadé
Elsa Regina
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 Prato
AP
Frizzo
Marcos Emílio Santos
ME
Izquierdo
Ivan
I
Elisabetsky
Elaine
E
Souza
Diogo Onofre
DO
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D001007:Anxiety / Q000517:prevention & control; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004546:Elapid Venoms / Q000633:toxicity; D005106:Exploratory Behavior / Q000187:drug effects; D006151:Guanosine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009498:Neurotoxins; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D004546:Elapid Venoms; D009498:Neurotoxins; D006151:Guanosine; C020273:dendrotoxin