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Currently available therapeutic drugs provide only symptomatic relief. Therefore, novel therapeutic strategies are needed to retard and\/or arrest the progressive loss of memory.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Scopolamine\u2010induced memory impairment provides a rapid and reversible phenotypic screening paradigm for cognition enhancement drug discovery. Male<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6<jats:styled-content style=\"fixed-case\">J<\/jats:styled-content>mice given scopolamine (1\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup>) were used to evaluate the ability of<jats:styled-content style=\"fixed-case\">LS<\/jats:styled-content>\u20101\u2013137, a novel sigma (\u03c31) receptor\u2010selective agonist, to improve the cognitive deficits associated with muscarinic antagonist administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">LS<\/jats:styled-content>\u20101\u2013137 is a high\u2010affinity (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>= 3.2\u2009nM) \u03c31 receptor agonist that is 80\u2010fold selective for \u03c31, compared with \u03c32 receptors.<jats:styled-content style=\"fixed-case\">LS<\/jats:styled-content>\u20101\u2013137 binds with low affinity at<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>2\u2010like (<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>2,<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>3 and<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>4) dopamine and muscarinic receptors.<jats:styled-content style=\"fixed-case\">LS<\/jats:styled-content>\u20101\u2013137 was found to partially reverse the learning deficits associated with scopolamine administration using a water maze test and an active avoidance task.<jats:styled-content style=\"fixed-case\">LS<\/jats:styled-content>\u20101\u2013137 treatment was also found to trigger the release of brain\u2010derived neurotrophic factor from rat astrocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>The \u03c31 receptor\u2010selective compound<jats:styled-content style=\"fixed-case\">LS<\/jats:styled-content>\u20101\u2013137 may represent a 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