PMID-39442746 – Semax Antidepressant and Antistress Effects

PMID-39442746 – Semax Antidepressant and Antistress Effects

Inozemtseva LS et al., "Antidepressant and antistress effects of Semax in rats subjected to chronic unpredictable stress," Eur J Pharmacol, 2024;983:177068. DOI: 10.1016/j.ejphar.2024.177068

Quick Reference

Property Value
PMID 39442746
DOI 10.1016/j.ejphar.2024.177068
Year 2024
Journal European Journal of Pharmacology
Study Type Animal in vivo
Evidence Level V
Sample Male rats, chronic unpredictable stress (CUS) model
Peptide(s) Studied Semax

Key Findings

  • Daily intranasal Semax administration reversed CUS-induced anhedonia (sucrose preference test), demonstrating antidepressant-like efficacy in a validated depression model.
  • Semax reversed CUS-induced body weight suppression and adrenal hypertrophy, indicating systemic antistress effects on the HPA axis.
  • Hippocampal BDNF protein levels, which were significantly decreased by CUS, were restored to near-normal levels by Semax treatment, supporting a neurotrophin-mediated mechanism of antidepressant action via melanocortin pathways.

Study Design

Male rats were subjected to a chronic unpredictable stress paradigm over several weeks to induce a depression-like phenotype. Semax was administered intranasally daily during the stress period. Behavioral endpoints (sucrose preference, body weight), organ weights (adrenal glands), and hippocampal BDNF protein levels were measured and compared between stressed + Semax, stressed + vehicle, and non-stressed control groups.

Limitations

  • Male rats only; sex-specific differences in stress response and melanocortin signaling were not addressed.
  • CUS model, while well-validated, does not fully recapitulate the complexity of human major depressive disorder.

Clinical Relevance

This is the most recent (2024) preclinical evidence supporting Semax's antidepressant potential, demonstrating that melanocortin pathway activation can reverse stress-induced behavioral and neurochemical deficits — relevant for clinicians considering Semax for mood and stress-related conditions.

Related

#research #animal-in-vivo #evidence-level-V