Antidepressant Effect of Intracerebroventricularly Administered Deltorphin Analogs in the Mouse Tail Suspension Test

Several studies have proposed delta opioid receptors as influential targets for developing novel antidepressants. Deltorphin (DLT) and deltorphin II (DLT-II) have high affinity and selectivity for delta opioid receptors; thus, it is likely that DLT analogs possess antidepressant-like effects. Based on this, we evaluated the effects of four DLT analogs (DLT-related synthetic peptides) on immobility behavior in the tail suspension test. Intracerebroventricular administration of DLT or [N-isobutyl-Gly(6)]DLT in mice significantly decreased immobile behavior. However, administration of DLT did not affect locomotor activity, whereas that of [N-isobutyl-Gly(6)]DLT significantly increased locomotion in mice. The effect of the shortened immobility time following DLT administration was counteracted by the administration of the selective delta(1) opioid receptor antagonist 7-benzylidenenaltrexone, but not by the selective delta(2) opioid receptor antagonist naltriben. These findings suggest that DLT has an antidepressant-like effect by activating the central delta(1) opioid receptor in mice.