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.
Role of the basolateral amygdala in mediating the effects of the fatty acid amide hydrolase inhibitor URB597 on HPA axis response to stress
CIFANI, Carlo;
2014-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
