Nitric oxide donor molsidomine attenuates psychotomimetic effects of the NMDA receptor antagonist MK-801.
There is experimental evidence indicating that the non-competitive NMDA receptor antagonist MK-801 impairs cognition and produces a series of schizophrenia-like symptoms in rodents (hypermotility, stereotypies, and ataxia). The present study was designed to investigate the efficacy of the nitric oxide (NO) donor molsidomine in counteracting these MK-801-induced behavioral effects in the rat. In a first study, post-training administration of molsidomine (at 4 but not 2 mg/kg) successfully antagonized MK-801-induced performance deficits in a recognition memory test. In a subsequent study, molsidomine (2 and 4 mg/kg) was shown to be unable to reverse MK-801-induced hypermotility but attenuated stereotypies (continuous movement whole cage, body sway, and head weaving) produced by MK-801. Moreover, at 4 mg/kg this NO donor counteracted MK-801-induced ataxia. Our findings indicate that molsidomine attenuates behavioral effects related to the hypofunction of the NMDA receptor suggesting that NO might be involved in the psychotomimetic effects of non-competitive NMDA receptor antagonists.
Pitsikas
Nikolaos
N
Department of Pharmacology, School of Medicine, University of Thessaly, Larissa, Greece. npitsikas@med.uth.gr
Zisopoulou
Styliani
S
Sakellaridis
Nikolaos
N
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006213:Hallucinogens / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects; D008981:Molsidomine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens; D020030:Nitric Oxide Donors; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D008981:Molsidomine