1. The hemoglobin derived peptide LVV-hemorphin-7 evokes behavioral effects mediated by oxytocin receptors.
- Author
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da Cruz KR, Turones LC, Camargo-Silva G, Gomes KP, Mendonça MM, Galdino P, Rodrigues-Silva C, Santos RAS, Costa EA, Ghedini PC, Ianzer D, and Xavier CH
- Subjects
- Animals, Anti-Anxiety Agents therapeutic use, Antidepressive Agents therapeutic use, Anxiety drug therapy, Anxiety metabolism, Depression drug therapy, Depression metabolism, Diazepam pharmacology, Hemoglobins therapeutic use, Hormone Antagonists pharmacology, Imipramine pharmacology, Male, Peptide Fragments therapeutic use, Rats, Rats, Wistar, Receptors, Oxytocin antagonists & inhibitors, Vasotocin analogs & derivatives, Vasotocin pharmacology, Anti-Anxiety Agents pharmacology, Antidepressive Agents pharmacology, Behavior, Animal drug effects, Hemoglobins pharmacology, Motor Activity drug effects, Peptide Fragments pharmacology, Receptors, Oxytocin metabolism
- Abstract
LVV-hemorphin-7 (LVV-h7) is bioactive peptide resulting from degradation of hemoglobin β-globin chain. LVV-h7 is a specific agonist of angiotensin IV receptor. This receptor belongs to the class of insulin-regulated aminopeptidases (IRAP), which displays oxytocinase activity. Herein, our aims were to assess whether: i) LVV-h7 modifies centrally organized behavior and cardiovascular responses to stress and ii) mechanisms underlying LVV-h7 effects involve activation of oxytocin (OT) receptors, probably as result of reduction of IRAP proteolytic activity upon OT. Adult male Wistar rats (270-370g) received (i.p.) injections of LVV-h7 (153nmol/kg), or vehicle (0.1ml). Different protocols were used: i) open field (OP) test for locomotor/exploratory activities; ii) Elevated Plus Maze (EPM) for anxiety-like behavior; iii) forced swimming test (FST) test for depression-like behavior and iv) air jet for cardiovascular reactivity to acute stress exposure. Diazepam (2mg/kg) and imipramine (15mg/kg) were used as positive control for EPM and FST, respectively. The antagonist of OT receptors (OTr), atosiban (1 and 0,1mg/kg), was used to determine the involvement of oxytocinergic paths. We found that LVV-h7: i) increased the number of entries and the time spent in open arms of the maze, an indicative of anxiolysis; ii) provoked antidepressant effect in the FS test; and iii) increased the exploration and locomotion; iv) did not change the cardiovascular reactivity and neuroendocrine responses to acute stress. Also, increases in locomotion and the antidepressant effects evoked by LVV-h7 were reverted by OTr antagonist. We conclude that LVV-h7 modulates behavior, displays antidepressant and anxiolytic effects that are mediated in part by oxytocin receptors., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Published
- 2017
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