Opioid System Critically Modulates Selank's Anti-Anxiety Effects in Mice

Selank, a synthetic heptapeptide analog of taftsin, is recognized for its anxiolytic (anxiety-reducing) properties. While its general effects are known, the precise mechanisms, especially its interaction with the endogenous opioid system, remain incompletely understood. This study specifically investigates how modulating the opioid system impacts the anxiolytic efficacy of Selank in different mouse strains with varying baseline anxiety levels.

Selank (0.25 mg/kg) alone demonstrated a clear anxiolytic effect in BALB/C mice, characterized by an increase in general locomotor activity, but showed no significant effect on the behavior of C57BL/6 mice in the OF test. Naloxone (1.0 mg/kg) administered alone evoked distinct behavioral changes: swift runaway in OF peripheral areas in BALB/C mice, while inducing a "freezing" reaction in C57BL/6 mice with an active stress response. Crucially, pretreatment with naloxone significantly attenuated the sensitivity to Selank's anxiolytic effects in BALB/C mice, indicating that an active opioid system is essential for Selank's full efficacy in this strain. Conversely, the response to Selank's anxiolytic effects was surprisingly increased in C57BL/6 mice following naloxone pretreatment, suggesting a complex, strain-dependent modulation by the opioid system. These findings strongly suggest that the activity of the enkephalin-opioid system plays a significant role in individual variability in response to Selank.