Levo-Stepholidine as a Potential Cognitive Enhancer: Insights into Executive Function and Memory Improvements.

Background/objectives: Levo-Stepholidine (-SPD), a compound extracted from Chinese herbs, has the potential to treat psychotic disorders where cognitive deficits are a critical challenge. -SPD displays a D1R agonism/D2R antagonism pharmacological profile, and its effect on cognitive function is still vague and lacks comprehensive study. Here, we investigated the impact of l-SPD on two core indexes of executive function, working memory and response inhibition, and learning and memory.

Methods: Using a delayed alternation T-maze task (DAT), we investigated the impact of -SPD on working memory, evaluated its effect on response inhibition using the stop-signal task (SST), and assessed the impact on learning and memory using trace fear conditioning in Sprague-Dawley rats. We further evaluated its effects on prefrontal glutamate receptor expression using western blot.

Results: Rats receiving -SPD made fewer errors in the T-maze, exhibited faster stop action in response to the stop signal, and showed longer-lasting memory retention. Molecular mechanism investigations reveal that -SPD upregulates the expression of prefrontal glutamate receptors. These results demonstrate that -SPD improves executive function and memory.

Conclusions: Here, we show the enhancement effect of l-SPD on cognitive function, which provides essential implicants for the treatment of cognitive deficits, which is a critical unmet need in psychiatric care.