Effect of riluzole on MK-801 and amphetamine-induced hyperlocomotion.
N-methyl-D aspartate (NMDA) antagonists, such as MK-801, and the dopamine indirect agonist amphetamine are pharmacological models used for the evaluation of putative new treatments for schizophrenia. Since the psychotomimetic effects of NMDA antagonists have recently been linked to their ability to increase glutamate release and since the glutamate release inhibitor riluzole prevented NMDA antagonist neurotoxicity, we evaluated the effect of riluzole on hyperlocomotion induced by MK-801 (0.25 mg/kg) and amphetamine (2.5 mg/kg). Mice pretreated with riluzole (3 mg/kg) did not influence baseline or MK-801-induced behavior, but 10 mg/kg produced moderate hypolocomotion alone and somewhat prolonged MK-801-induced hyperlocomotion. Pretreatment with riluzole 10 mg/kg, but not 3 mg/kg, had a moderately depressant effect both on spontaneous and amphetamine-induced locomotion. Taken together, these results suggest that riluzole would not be particularly effective as a treatment for schizophrenia and the neurotoxic and behavioral effect of NMDA antagonists do not clearly correlate.
Lourenço Da Silva
Adriana
A
Laboratório de Neurobiologia Experimental, Departamento de Bioquímica, ICBS, UFRGS, Porto Alegre, Brazil. drlara@pucrs.br
Hoffmann
Anselmo
A
Dietrich
Marcelo O
MO
Dall'Igna
Oscar P
OP
Souza
Diogo O
DO
Lara
Diogo R
DR
D000661:Amphetamine / Q000009:adverse effects*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000009:adverse effects; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule / Q000662:veterinary; D004347:Drug Interactions; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D019782:Riluzole / Q000494:pharmacology / Q000627:therapeutic use*
D000697:Central Nervous System Stimulants; D018696:Neuroprotective Agents; D016291:Dizocilpine Maleate; D019782:Riluzole; D000661:Amphetamine