title: Role of the basolateral amygdala in mediating the effects of the fatty acid amide hydrolase inhibitor URB597 on HPA axis response to stress.
abstract: The endocannabinoid system is an important regulator of neuroendocrine and behavioral adaptation in stress related disorders thus representing a novel potential therapeutic target. The aim of this study was to determine the effects of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on stress mediators of HPA axis and to study the role of the basolateral amygdala (BLA) in responses to forced swim stress. Systemic administration of URB597 (0.1 and 0.3mg/kg) reduced the forced swim stress-induced activation of HPA axis. More specifically, URB597 decreased stress-induced corticotropin-releasing hormone (CRH) mRNA expression in the paraventricular nucleus (PVN) of the hypothalamus, and pro-opiomelanocortin (POMC) mRNA expression dose-dependently in pituitary gland without affecting plasma corticosterone levels. URB597 treatment also attenuated stress-induced neuronal activation of the amygdala and PVN, and increased neuronal activation in the locus coeruleus (LC) and nucleus of solitary tract (NTS). Injection of the CB1 receptor antagonist AM251 (1ng/side) in the BLA significantly attenuated URB597-mediated effects in the PVN and completely blocked those induced in the BLA. These results suggest that the BLA is a key structure involved in the anti-stress effects of URB597, and support the evidence that enhancement of endogenous cannabinoid signaling by inhibiting FAAH represents a potential therapeutic strategy for the management of stress-related disorders.
authors.affiliation: Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, 00185, Italy.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Bedse
authors.affiliation: Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, 00185, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Colangeli
authors.affiliation: Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, 00185, Italy.
authors.forename: Angelo M
authors.initials: AM
authors.lastname: Lavecchia
authors.affiliation: Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, 00185, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Romano
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti - Department of Biochemical Sciences, Sapienza University of Rome, Rome 00185, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Altieri
authors.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, 62032, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Cifani
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia 71100, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Cassano
authors.affiliation: Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, 00185, Italy. Electronic address: silvana.gaetani@uniroma1.it.
authors.forename: Silvana
authors.initials: S
authors.lastname: Gaetani
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D066272:Basolateral Nuclear Complex / Q000187:drug effects / Q000378:metabolism*; D001549:Benzamides / Q000494:pharmacology*; D002219:Carbamates / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D010913:Pituitary-Adrenal System; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013315:Stress, Psychological / Q000188:drug therapy*; D013550:Swimming / Q000523:psychology; D013997:Time Factors
chemical_list: D001549:Benzamides; D002219:Carbamates; D004791:Enzyme Inhibitors; D010880:Piperidines; D011720:Pyrazoles; D012333:RNA, Messenger; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C103505:AM 251; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone
keywords: Amygdala; CRH; Fatty acid amide hydrolase; Forced swimming stress; POMC; URB597