The Antidepressant-like Effect Of Hunman Opiorphin Via Opioid-dependent Pathways In Mice

Opiorphin is the endogeous dual inhibitor of two peptidase APN and NEP. In the present study, we investigated the antidepressive activity of opiorphin with central administration in the forced swim test in mice. Intracerebroventricular (i.c.v.) administration of opiorphin (50,100,200, 300μg/kg) dose-dependently decreased the immobility time, which indicated that opiorphin had an antidepressant-like effect. This effect was reversed by nonselective opioid receptor antagonist naloxone. Since enkephalin can activate bothδandμreceptors, opiorphin was co-administaed withδ-selective antagonist naltrindole orμ-selectiveβ-FNA, and the results showed that the antidepressant-like effect of opiorphin was blocked by bothδandμreceptors antagonists. The dates suggested that central administration of opiorphin produced an antidepressant-like effect by activating bothμandδopioid receptors indirectly. Inorder to eliminate the possibility of a false-positive result in the forced swim test, locomotor activity was checked. In view of the fact that some drugs induced different responses in non-habituated or habituated mice, we checked both kinds of mice. Opiorphin had no influence on non-habituated mice, though had weake effect on habituated mice. In addition, mice treated with opiorphin did not display any convulsive behaviors.