1. ¹Laboratory of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
2. ²Laboratory of Experimental Neuropsychopharmacology, CNRS FRE 2735, IFRMP 23, Faculty of Medicine & Pharmacy, University of Rouen, Rouen Cedex, France

Correspondence: Dr J-C do Rego, Laboratoire de Neuropsychopharmacologie Expérimentale, CNRS FRE 2735, IFRMP 23, UFR de Médecine et Pharmacie, 22, Boulevard Gambetta, 76183 Rouen Cedex, France. Tel: +33 2 35148602; Fax: +33 2 35148603; E-mail: jean-claude.dorego@univ-rouen.fr

Received 31 January 2006; Revised 28 April 2006; Accepted 30 May 2006; Published online 5 July 2006.

Abstract

Endomorphin-1 (Tyr-Pro-Trp-Phe-NH₂) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH₂) are two recently isolated -opioid selective peptides with a potent antinociceptive activity, involved in a number of physiological processes, including food intake, vasomotricity, sexual behavior, as well as neuroendocrine and cardiorespiratory functions. The neuroanatomical distribution of endomorphins prompted us to study their antidepressant activity in two animal behavioral models of depression: forced-swimming and tail-suspension tests. In both tests, the intracerebroventricular (i.c.v.) injection of either endomorphin-1 or endomorphin-2 significantly decreased the duration of immobility, interpreted as an expression of 'behavioral despair', which could be related to the depression syndrome. These effects of endomorphins did not result from the stimulation of the animal motor activity. We have also demonstrated that the antidepressant-like effect of endomorphins was antagonized by the universal opioid antagonist, naloxone and the -opioid receptor selective antagonist, -funaltrexamine. In contrast, this effect was not antagonized by - and -opioid receptor selective antagonists, naltrindole and nor-binaltorphimine, respectively. The results of the present study demonstrate that endomorphin-1 and endomorphin-2 produce potent antidepressant-like effects after i.c.v. injection in mice. We may suggest that endomorphins and the -opioid receptors might be involved in the physiopathology of depressive disorders, and that the endomorphinergic system could serve as a novel target for the development of antidepressant drugs.