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The dual blocker of FAAH/TRPV1 N-arachidonoylserotonin reverses the behavioral despair induced by stress in rats and modulates the HPA-axis
A. Navarria, A. Tamburella, FA. Iannotti, V. Micale, G. Camillieri, L. Gozzo, R. Verde, R. Imperatore, GM. Leggio, F. Drago, V. Di Marzo,
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- amidohydrolasy antagonisté a inhibitory genetika metabolismus MeSH
- chování zvířat účinky léků MeSH
- endokanabinoidy metabolismus MeSH
- fyzické omezení MeSH
- glyceridy metabolismus MeSH
- kationtové kanály TRPV antagonisté a inhibitory genetika metabolismus MeSH
- kortikosteron krev MeSH
- krysa rodu rattus MeSH
- kyseliny arachidonové metabolismus farmakologie terapeutické užití MeSH
- mozek účinky léků metabolismus MeSH
- mozkový neurotrofický faktor genetika metabolismus MeSH
- plavání MeSH
- polynenasycené alkamidy metabolismus MeSH
- potkani Wistar MeSH
- psychický stres krev farmakoterapie metabolismus MeSH
- serotonin analogy a deriváty farmakologie terapeutické užití MeSH
- systém hypofýza - nadledviny MeSH
- systém hypotalamus-hypofýza MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In recent years, several studies have explored the involvement of the deregulation of the hypothalamus-pituitary-adrenal (HPA) axis in the pathophysiology of stress-related disorders. HPA hyper-activation as a consequence of acute/chronic stress has been found to play a major role in the neurobiological changes that are responsible for the onset of such states. Currently available medications for depression, one of the most relevant stress-related disorders, present several limitations, including a time lag for treatment response and low rates of efficacy. N-Arachidonoylserotonin (AA-5-HT), a dual blocker at fatty acid amide hydrolase (FAAH, the enzyme responsible for the inactivation of the endocannabinoid anandamide) and transient receptor potential vanilloid type-1 channel (TRPV1), produces anxiolytic-like effects in mice. The present study was designed to assess the capability of AA-5-HT to reverse the behavioral despair following exposure to stress in rats and the role of the HPA-axis. Behavioral tasks were performed, and corticosterone and endocannabinoid (anandamide and 2-arachidonoylglycerol) levels were measured in selected brain areas critically involved in the pathophysiology of stress-related disorders (medial PFC and hippocampus) under basal and stress conditions, and in response to treatment with AA-5-HT. Our data show that AA-5-HT reverses the rat behavioral despair in the forced swim test under stress conditions, and this effect is associated with the normalization of the HPA-axis deregulation that follows stress application and only in part with elevation of anandamide levels. Blockade of FAAH and TRPV1 may thus represent a novel target to design novel therapeutic strategies for the treatment of stress-related disorders.
Citace poskytuje Crossref.org
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- $a Navarria, Andrea $u Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania Medical School, Catania, Italy.
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- $a The dual blocker of FAAH/TRPV1 N-arachidonoylserotonin reverses the behavioral despair induced by stress in rats and modulates the HPA-axis / $c A. Navarria, A. Tamburella, FA. Iannotti, V. Micale, G. Camillieri, L. Gozzo, R. Verde, R. Imperatore, GM. Leggio, F. Drago, V. Di Marzo,
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- $a In recent years, several studies have explored the involvement of the deregulation of the hypothalamus-pituitary-adrenal (HPA) axis in the pathophysiology of stress-related disorders. HPA hyper-activation as a consequence of acute/chronic stress has been found to play a major role in the neurobiological changes that are responsible for the onset of such states. Currently available medications for depression, one of the most relevant stress-related disorders, present several limitations, including a time lag for treatment response and low rates of efficacy. N-Arachidonoylserotonin (AA-5-HT), a dual blocker at fatty acid amide hydrolase (FAAH, the enzyme responsible for the inactivation of the endocannabinoid anandamide) and transient receptor potential vanilloid type-1 channel (TRPV1), produces anxiolytic-like effects in mice. The present study was designed to assess the capability of AA-5-HT to reverse the behavioral despair following exposure to stress in rats and the role of the HPA-axis. Behavioral tasks were performed, and corticosterone and endocannabinoid (anandamide and 2-arachidonoylglycerol) levels were measured in selected brain areas critically involved in the pathophysiology of stress-related disorders (medial PFC and hippocampus) under basal and stress conditions, and in response to treatment with AA-5-HT. Our data show that AA-5-HT reverses the rat behavioral despair in the forced swim test under stress conditions, and this effect is associated with the normalization of the HPA-axis deregulation that follows stress application and only in part with elevation of anandamide levels. Blockade of FAAH and TRPV1 may thus represent a novel target to design novel therapeutic strategies for the treatment of stress-related disorders.
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