Human opiorphin is a naturally occurring antidepressant acting selectively on enkephalin-dependent delta-opioid pathways

• Autorzy: Javelot H. , Messaoudi M. , Garnier S. , Rougeot C.
• Języki publikacji: EN

Abstrakty

EN

Human opiorphin protects enkephalins from degradation by human neutral endopeptidase and aminopeptidase-N and inhibits pain perception in various behavioral rodent models of pain via endogenous enkephalin-related activation of opioidergic pathways. In addition to pain control, endogenous opioid pathways are also implicated in the modulation of emotion-related behaviors. Thus, we explored the dose-dependent motivational responses induced by opiorphin using the forced swim test, the standard rat model of depression. In addition, to further understand the endogenous events triggered by opiorphin, we investigated the specific involvement of µ- or -opioid receptor-dependent pathways. In parallel, the locomotor activity test was used to detect possible sedation or hyperactivity. Here, we report for the first time that at 1-2 mg/kg i.v. doses, opiorphin elicited antidepressant-like effects by activating endogenous -opioidergic pathways, since that activation was reversed by the selective -opioid antagonist naldrindole (10 mg/kg i.p.). The antidepressive behavioral responses exerted by opiorphin are specific at systemically active doses. Treated-rats did not develop either hypo- or hyper-active responses in a locomotor test or amnesic behavioral response in the passive avoidance rat model. In addition, opiorphin did not induce either anxiolytic-, or anxiogenic-like responses in the conditioned defensive burying test. Taking the data together, we conclude that opiorphin is able to elicit antidepressant-like effects, mediated via -opioid receptor-dependent pathways, by modulating the concentrations of endogenous enkephalin released in response to specific physical and/or psychological stimuli. Thus, opiorphin or optimized derivatives is a promising single candidate to treat disorders that include both pain and mood disorders, particularly depression.

Słowa kluczowe

EN

opiorphin; human opiorphin; antidepressant; opioid pathway; neutral endopeptidase; aminopeptidase-N; pain control; endogenous opioid; enkephalin-inactivating neutral endopeptidase inhibitor; depression; learning-memory; locomotion

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2010
• Tom: 61
• Numer: 3
• Opis fizyczny: p.355-362,fig.,ref.

Twórcy

autor

Javelot H.

• Institut Pasteur - Unite de Biochimie Structurale et Cellulaire/URA2185 - CNRS, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France

autor

Messaoudi M.

autor

Garnier S.

autor

Rougeot C.

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