The dual blocker of FAAH/TRPV1 N-arachidonoylserotonin reverses
the behavioral despair induced by stress in rats and modulates
the HPA-axis

J 2014

The dual blocker of FAAH/TRPV1 N-arachidonoylserotonin reverses the behavioral despair induced by stress in rats and modulates the HPA-axis

NAVARRIA, A., A. TAMBURELLA, F.A. IANNOTTI, Vincenzo MICALE, G. CAMILLIERI et. al.

Basic information

Original name

The dual blocker of FAAH/TRPV1 N-arachidonoylserotonin reverses the behavioral despair induced by stress in rats and modulates the HPA-axis

Authors

NAVARRIA, A. (380 Italy), A. TAMBURELLA (380 Italy), F.A. IANNOTTI (380 Italy), Vincenzo MICALE (380 Italy, guarantor, belonging to the institution), G. CAMILLIERI (380 Italy), L. GOZZO (380 Italy), R. VERDE (380 Italy), R. IMPERATORE (380 Italy), G.M. LEGGIO (380 Italy), F. DRAGO (380 Italy) and Marzo V. DI (380 Italy)

Edition

PHARMACOLOGICAL RESEARCH, London, ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2014, 1043-6618

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.408

RIV identification code

RIV/00216224:14740/14:00078064

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1016/j.phrs.2014.04.014

UT WoS

000341474400016

Keywords in English

N-Arachidonoylserotonin; HPA-axis; Stress; FAAH; TRPV1

Abstract

V originále

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-FIT. 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. (C) 2014 Elsevier Ltd. All rights reserved.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

Citovat

NAVARRIA, A., A. TAMBURELLA, F.A. IANNOTTI, Vincenzo MICALE, G. CAMILLIERI, L. GOZZO, R. VERDE, R. IMPERATORE, G.M. LEGGIO, F. DRAGO and Marzo V. DI. The dual blocker of FAAH/TRPV1 N-arachidonoylserotonin reverses the behavioral despair induced by stress in rats and modulates the HPA-axis. PHARMACOLOGICAL RESEARCH. London: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2014, vol. 87, September, p. 151-159. ISSN 1043-6618. Available from: https://dx.doi.org/10.1016/j.phrs.2014.04.014.

@article{1215230,
   author = {Navarria, A. and Tamburella, A. and Iannotti, F.A. and Micale, Vincenzo and Camillieri, G. and Gozzo, L. and Verde, R. and Imperatore, R. and Leggio, G.M. and Drago, F. and Di, Marzo V.},
   article_location = {London},
   article_number = {September},
   doi = {http://dx.doi.org/10.1016/j.phrs.2014.04.014},
   keywords = {N-Arachidonoylserotonin; HPA-axis; Stress; FAAH; TRPV1},
   language = {eng},
   issn = {1043-6618},
   journal = {PHARMACOLOGICAL RESEARCH},
   title = {The dual blocker of FAAH/TRPV1 N-arachidonoylserotonin reverses the behavioral despair induced by stress in rats and modulates the HPA-axis},
   url = {http://www.sciencedirect.com/science/article/pii/S104366181400067X},
   volume = {87},
   year = {2014}
}

TY  - JOUR
ID  - 1215230
AU  - Navarria, A. - Tamburella, A. - Iannotti, F.A. - Micale, Vincenzo - Camillieri, G. - Gozzo, L. - Verde, R. - Imperatore, R. - Leggio, G.M. - Drago, F. - Di, Marzo V.
PY  - 2014
TI  - The dual blocker of FAAH/TRPV1 N-arachidonoylserotonin reverses the behavioral despair induced by stress in rats and modulates the HPA-axis
JF  - PHARMACOLOGICAL RESEARCH
VL  - 87
IS  - September
SP  - 151-159
EP  - 151-159
PB  - ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
SN  - 10436618
KW  - N-Arachidonoylserotonin
KW  - HPA-axis
KW  - Stress
KW  - FAAH
KW  - TRPV1
UR  - http://www.sciencedirect.com/science/article/pii/S104366181400067X
L2  - http://www.sciencedirect.com/science/article/pii/S104366181400067X
N2  - 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-FIT. 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. (C) 2014 Elsevier Ltd. All rights reserved.
ER  -

NAVARRIA, A., A. TAMBURELLA, F.A. IANNOTTI, Vincenzo MICALE, G. CAMILLIERI, L. GOZZO, R. VERDE, R. IMPERATORE, G.M. LEGGIO, F. DRAGO and Marzo V. DI. The dual blocker of FAAH/TRPV1 N-arachidonoylserotonin reverses the behavioral despair induced by stress in rats and modulates the HPA-axis. \textit{PHARMACOLOGICAL RESEARCH}. London: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2014, vol.~87, September, p.~151-159. ISSN~1043-6618. Available from: https://dx.doi.org/10.1016/j.phrs.2014.04.014.

Detailed Information on Publication Record