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

Author(s)

Borges-Assis, Anna Barbara ; Uliana, Daniela Lescano ; Hott, Sara Cristina ; Guimara, Francisco Silveira ; Lisboa, Sabrina Francesca ; Resstel, Leonardo Barbosa Moraes

• Document type: Journal article
• Source: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY; v. 125, p. 12-pg., 2023-07-13.

Abstract

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 postsynaptic 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 anxietyrelated 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. (AU)

• FAPESP's process: 17/16913-6 - Possible involvement of the endocannabinoid system in the bed nucleus of stria terminalis on the contextual fear conditioning responses in rats
• Grantee: Anna Bárbara Borges de Assis
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/24304-0 - New perspectives in the use of drugs that modify atypical neurotransmitters in the treatment of neuropsychiatric disorders
• Grantee: Francisco Silveira Guimaraes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/17626-7 - Cellular and molecular mechanisms involved in the role of atypical neurotransmitters in neuropsychiatric disorders
• Grantee: Francisco Silveira Guimaraes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/19731-6 - Identification of epigenetic mechanisms induced by stress which modulate endocannabinoid signaling and neuroimmunological mechanisms as new therapeutic targets to treat the posttraumatic stress disorder (PTSD)
• Grantee: Sabrina Francesca de Souza Lisboa
• Support Opportunities: Research Grants - Young Investigators Grants