Guanosine selectively inhibits locomotor stimulation induced by the NMDA antagonist dizocilpine.
Guanosine has been shown to modulate glutamate system by stimulating astrocytic glutamate uptake. Recent evidence suggest that the locomotor effects of NMDA receptor antagonists, an animal model of schizophrenia, is associated with activation of non-NMDA glutamatergic receptors caused by increased glutamate release. The present work was undertaken to evaluate whether guanosine could have influence on the hyperlocomotion induced in mice by dizocilpine (MK-801), a NMDA antagonist. We also evaluated the effect of guanosine on the hyperlocomotion induced by the indirect dopamine agonist amphetamine, and by the non-selective adenosine receptor antagonist caffeine. Guanosine (7.5 mg/kg) produced an attenuation of about 60% on the hyperlocomotion induced by dizocilpine (0.25 mg/kg), whereas it did not affect the hyperlocomotion induced by amphetamine (5 mg/kg) or caffeine (30 mg/kg). Guanosine pre-treatment did not affect total spontaneous locomotion in all experiments. To test neuronal pathway selectivity, we evaluated MK-801 against guanosine in a working memory paradigm (spontaneous alternation task). Guanosine did not reverted the impairment caused by MK-801 in the spontaneous alternation test, and when administered alone also presented an amnesic effect. The results are discussed based on the current hypothesis of locomotor activation induced by the psychoactive drugs studied. Further studies are necessary to evaluate if guanosine could have clinical utility for the treatment of schizophrenia.
Tort
Adriano B L
AB
Departamento de Bioquímica, ICBS, Universidade Federal do Grande do Sul (UFRGS), Rua Ramiro Barcellos 2600, anexo, 90035003 Porto Alegre, Brazil. adrianotort@hotmail.com
Mantese
Carlos E
CE
dos Anjos
Gabriel M
GM
Dietrich
Marcelo O
MO
Dall'Igna
Oscar P
OP
Souza
Diogo O
DO
Lara
Diogo R
DR
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D002110:Caffeine / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006151:Guanosine / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000697:Central Nervous System Stimulants; D016194:Receptors, N-Methyl-D-Aspartate; D006151:Guanosine; D002110:Caffeine; D016291:Dizocilpine Maleate; D000661:Amphetamine