The findings convincingly demonstrate the antidepressant potential of S-(+)-mecamylamine through its modulation of glutamate release and serotonergic neuron firing. However, the exclusive use of male rats limits the applicability of the results across sexes. Given the evidence for sex-dependent differences in stress-related behaviors and serotonergic systems, could the authors discuss how these findings might differ in female models? Moreover, are there plans for follow-up studies to investigate sex-specific responses to S-mecamylamine or its combination therapies?