MK-801 (30-100 μg/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 μg/kg, SC), putative σ 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 σ antagonist. These findings suggest that, at low doses, σ ligands may modulate the N-methyl-d-aspartate dependent memory processes.
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