PHARMACOLOGICAL AUGMENTATION OF ENDOCANNABINOID SIGNALING REDUCES THE STRESS RESPONSE TO IMMOBILIZATION

RÍOS, CARLOS EZEQUIEL; DE LAURENTIIS, ANDREA; GALLINO, SOFÍA; CORREA, FERNANDO; SURKIN, PABLO NICOLÁS; FERNÁNDEZ-SOLARI, JAVIER

MAR DEL PLATA

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2016

SAIC

Stress activates the hypothalamic-pituitary-adrenal (HPA) axisincreasing glucocorticoids and several neurotransmitters. Componentsof the endocannabinoid (eCB) system (ECS) are presentthroughout the HPA and both systems interact extensively in theregulation of stress response. The study focuses on ECS regulationof acute neurogenic stress response. Sprague-Dawley malerats were immobilized for 30 min. Each group received intracerebroventricular(icv): anandamide (AEA, 50ng/5ul), or the inhibitorof FAAH (URB597, 50ugr/5ul), or antagonists for CB1 (AM251,500ng/5ul) or CB2 (AM630, 500ng/5ul) or vehicle 15min beforestress. Others received intraperitoneal (ip) Methanandamide(2.5mg/kg), AM251 (2mg/kg), URB597 (0.3mg/kg) or vehicle.Corticosterone (CORT) by RIA and the hypothalamic nitric oxidesynthase (NOS) activity were determined. Control and stressedrats were sacrificed 4hs after stress, CORT and hypothalamicand adrenal CB1, CB2 and TRPV1 mRNAs determined by PCRand qPCR. Adrenals from control rats were incubated in bufferKrebs (30 min) with ACTH (10-9M) alone or with AEA (10-9M)or URB597 (3uM) or AM251 (10-5M) or vehicle. Media CORTand tissue NOS activity were determined. Our results show thatAEA blocks the increase of CORT at central and peripherallevels (p