Antidepressant-Like Effect of Endomorphin-1 and Endomorphin-2 in Mice

Abstract

Endomorphin-1 (Tyr-Pro-Trp-Phe-NH 2 ) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH 2 ) are two recently isolated m-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 m-opioid receptor selective antagonist, b-funaltrexamine. In contrast, this effect was not antagonized by d-and k-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 m-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. Neuropsychopharmacology (2007) 32, 813-821.

Pituitary Adenylate Cyclase-Activating Polypeptide Inhibits Food Intake in Mice Through Activation of the Hypothalamic Melanocortin System

“…Central administration (10 ml per mouse) of saline or peptide solutions (VIP, PACAP alone or in combination with PACAP6-38) was made, free hand, in the ventricle of Swiss albinos CD1 mice, according to the procedure of Haley and McCormick (1957), similar to that employed by Fichna et al (2007) and Do . To evaluate the effect of SHU9119 on PACAP-induced inhibition of food intake, mice were injected i.c.v.…”

Design, synthesis and pharmacological evaluation of novel endomorphin analogues with multiple structural modifications

“…Among the tested analogues compounds 10 4 . Such modifications yielded the analogues with increased proteolytic stability while retaining or enhancing the biological activity.…”

Identificação e caracterização de peptídeos opioides presentes na fração proteica dos grãos de Coffea arabica

“…Existem Além do sistema límbico, alguns peptídeos opioides modulam os processos de neurotransmissão nas vias serotoninérgicas, dopaminérgicas, noradrenérgicas, que regulam fisiopatologias de desordens depressivas (Fichna et al, 2007). Dentre esses, a neurotransmissão de serototina participa da regulação do estresse, do humor e do controle do apetite.…”

“…Essas vias neurotransmissoras são consideradas alvos terapêuticos promissores para o tratamento de desordens associadas ao humor e os peptídeos opioides apresentam o potencial de agente terapêutico para o desenvolvimento de novos fármacos antidepressivos (Fichna et al, 2007).…”

“…Ela possui atividade antinociceptiva e está localizada, principalmente, no mesencéfalo, locus coerelus, no hipotálamo, substância gelatinosa e corno dorsal da medula espinhal. As endomorfinas podem ser clivadas por peptidases (exo e endopeptidases) no meio extracelular e também no meio intracelular (Fichna et al, 2007 Também foram utilizados a Leu-encefalina como controle positivo, um peptídeo endógeno que atua sobre receptores opioides, e quando administrada por via i.p. conjugada com a glicose atravessa a barreira hematoencefálica por meio de difusão mediada pelo transportador para glicose (GLU-T1) (Li et al, 2012;Polt et al,1994).…”