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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

The Dual Blocker of FAAH/TRPV1 N-arachidonoylserotonin Reverses the Behavioral Despair Induced by Stress in Rats and Modulates the HPA-axis

Andrea Navarria, Alessandra Tamburella, Fabio A Iannotti, Vincenzo Micale, Giovanni Camillieri, Lucia Gozzo, Roberta Verde, Roberta Imperatore, Gian Marco Leggio, Filippo Drago, Vincenzo Di Marzo

Pharmacol Res. 2014 Sep;87:151-9.

PMID: 24861565

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP187947371	Arachidonoylserotonin		187947-37-1	Price

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