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

• Published in: Biological & pharmaceutical bulletin Vol. 45; no. 4; pp. 538 - 541
• Main Authors: Nakagawasai, Osamu, Takahashi, Kohei, Ambo, Akihiro, Onuma, Kentaro, Takahashi, Naruya, Nemoto, Wataru, Tan-No, Koichi
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.04.2022; Japan Science and Technology Agency
• Subjects: Animals; antidepressant; Antidepressants; Antidepressive Agents - pharmacology; deltorphin; Deltorphin II; Hindlimb Suspension; Intracerebroventricular administration; Locomotion; Locomotor activity; Mice; Narcotic Antagonists - pharmacology; Narcotics; Oligopeptides; Opioid receptors; Receptors, Opioid, delta; Synthetic peptides; δ1 receptor; δ1 receptor; antidepressant; deltorphin
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b21-01078

Several studies have proposed δ opioid receptors as influential targets for developing novel antidepressants. Deltorphin (DLT) and deltorphin II (DLT-II) have high affinity and selectivity for δ 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-Gly6]DLT in mice significantly decreased immobile behavior. However, administration of DLT did not affect locomotor activity, whereas that of [N-isobutyl-Gly6]DLT significantly increased locomotion in mice. The effect of the shortened immobility time following DLT administration was counteracted by the administration of the selective δ1 opioid receptor antagonist 7-benzylidenenaltrexone, but not by the selective δ2 opioid receptor antagonist naltriben. These findings suggest that DLT has an antidepressant-like effect by activating the central δ1 opioid receptor in mice.