Bed nucleus of the stria terminalis CB1 receptors and the FAAH enzyme modulate anxiety behavior depending on previous stress exposure.

Autor: Borges-Assis AB; Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Uliana DL; Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, USA., Hott SC; Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Guimarães FS; Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Lisboa SF; Department of BioMolecular Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: sabrinalisboa@usp.br., Resstel LBM; Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: leoresstel@fmrp.usp.br.
Jazyk: angličtina
Zdroj: Progress in neuro-psychopharmacology & biological psychiatry [Prog Neuropsychopharmacol Biol Psychiatry] 2023 Jul 13; Vol. 125, pp. 110739. Date of Electronic Publication: 2023 Mar 03.
DOI: 10.1016/j.pnpbp.2023.110739
Abstrakt: The endocannabinoid (eCB) anandamide (AEA) is synthesized on-demand in the post-synaptic terminal and can act on presynaptic cannabinoid type 1 (CB1) receptors, decreasing the release of neurotransmitters, including glutamate. AEA action is ended through enzymatic hydrolysis via FAAH (fatty acid amid hydrolase) in the post-synaptic neuron. eCB system molecules are widely expressed in brain areas involved in the modulation of fear and anxiety responses, including the Bed Nucleus of the Stria Terminalis (BNST), which is involved in the integration of autonomic, neuroendocrine, and behavioral regulation. The presence of the CB1 and FAAH was described in the BNST; however, their role in the modulation of defensive reactions is not fully comprehended. In the present work we aimed at investigating the role of AEA and CB1 receptors in the BNST in modulating anxiety-related behaviors. Adult male Wistar rats received local BNST injections of the CB1 receptor antagonist AM251 (0.1-0.6 nmol) and/or the FAAH inhibitor (URB597; 0.001-0.1 nmol) and were evaluated in the elevated plus maze (EPM) test, with or without previous acute restraint stress (2 h) exposure, or in the contextual fear conditioning. We observed that although AM251 and URB597 had no effects on the EPM, they increased and decreased, respectively, the conditioned fear response. Supporting a possible influence of stress in these differences, URB597 was able to prevent the restraint stress-induced anxiogenic effect in the EPM. The present data, therefore, suggest that eCB signaling in the BNST is recruited during more aversive situations to counteract the stress effect.
Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE