A single dose of the short-acting psychedelic 5-MeO-DMT alters expression of genes related to plasticity and neuronal activity in specific brain regions of mice, including the anterior cingulate cortex, basolateral amygdala, and ventral hippocampus. Immediate early genes Arc and Zif268 changed within hours, while TRIP8b, a modulator of neuronal activity, increased in the ventral hippocampus after five days. Behaviorally, 5-MeO-DMT produced mixed anxiety-reducing and anxiety-increasing effects in standard tests, but mice pre-treated with the compound and then exposed to acute stress showed lower corticosterone levels and strong anxiety-reducing effects. The findings suggest molecular pathways through which 5-MeO-DMT may produce anxiolytic effects.
A single high dose of the short-acting psychedelic 5-MeO-DMT alters gene expression in specific brain regions of mice, including the anterior cingulate cortex, basolateral amygdala, ventral hippocampus CA1 region, and dentate gyrus. The compound changed mRNA levels of immediate early genes Arc and Zif268 in several regions and increased TRIP8b expression in the ventral hippocampus after five days. Behaviorally, treated mice showed mixed anxiety-reducing and anxiety-increasing effects in standard tests. However, when pre-treated mice were subjected to acute stress, they had lower corticosterone levels and robust anxiety-reducing effects. These findings suggest molecular actions of 5-MeO-DMT related to its potential anxiolytic effects.