Effect of Riluzole on MK-801 and Amphetamine-Induced Hyperlocomotion

Abstract

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.

Glutamatergic Modulators: The Future of Treating Mood Disorders?

“…In addition to the clinical evidence, animal studies have shown that long-term use of riluzole induces antidepressant- and antimanic-like behaviors in rodents 96,97. It is important to note, however, that despite its efficacy, no evidence suggests that riluzole acts more rapidly than existing antidepressants, though it may be a reasonable therapeutic option in treatment-resistant cases.…”

Targeting Glutamatergic Signaling for the Development of Novel Therapeutics for Mood Disorders

“…Riluzole has not yet been studied in the manic phase of BPD, although it purportedly reduced hyperactivity caused by amphetamine in an animal model of mania [54]; these data suggest that riluzole should be considered for further testing in other phases of BPD.…”

New Therapeutic Targets for Mood Disorders

“…Riluzole also enhances glutamate reuptake and activates synthesis of neurotrophins [108, 109]. Interestingly, one preclinical study found that pretreatment with 10 mg/kg riluzole (but not 3 mg/kg) moderately reduced amphetamine-induced hyperlocomotion [110], which could suggest potential antimanic efficacy.…”