Low dose of 1,3-di(2-tolyl)guanidine (DTG) attenuates MK-801-induced spatial working memory impairment in mice.
MK-801 (30-100 micrograms/kg, SC) impaired spontaneous alternation behavior of mice, a behavior related to the spatial working memory. 1,3-Di-(2-tolyl)guanidine (DTG), (+)-pentazocine and (+)-SKF 10,047 (100 micrograms/kg, SC), putative sigma agonists, administered 10 min before MK-801, partially but significantly reversed the impairment, without affecting the concomitant hyperlocomotion. The antagonizing effects by DTG were prevented by BMY-14802 (5 mg/kg, IP), a purported sigma antagonist. These findings suggest that, at low doses, sigma ligands may modulate the N-methyl-D-aspartate dependent memory processes.
Department of Neuropsychopharmacology, Nagoya University School of Medicine, Japan.
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T
Maurice
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Hiramatsu
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J
Itoh
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Kameyama
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Hasegawa
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Nabeshima
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000927:Anticonvulsants / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D010423:Pentazocine / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D017480:Receptors, sigma / Q000819:agonists / Q000037:antagonists & inhibitors; D013028:Space Perception / Q000187:drug effects*
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D006146:Guanidines; D011743:Pyrimidines; D017480:Receptors, sigma; C050408:alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; D016291:Dizocilpine Maleate; C012134:SK&F 10047; D010620:Phenazocine; C050232:1,3-ditolylguanidine; D010423:Pentazocine