The role of endocannabinoid signaling in the chronic mild stress-induced depressive-like behavior elicited by Eif4e -bp1/2 double knockout mice submitted to a psychobiological test of risk assessment

• Grant number: 24/08300-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: January 01, 2025
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Norberto Cysne Coimbra
• Grantee: Weverton Castro Coelho-Silva
• Supervisor: Argel Aguilar Valles
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Carleton University, Canada
• Associated to the scholarship: 23/01003-5 - Study of the role of endocannabinoid and endovanilloid signaling in the paleostriatum in mental disorders on depressive-like behavior and instinctive fear of a psychobiological risk assessment test, BP.DR

Abstract

There is a growing interest in understanding neural behaviors associated with anxiety and depression. Innovative studies exploring the biochemical and pharmacological mechanisms of cannabinoids offer promising avenues for developing new therapeutic targets for mental disorders treatment. The rapamycin-target protein complex 1 (mTOR1) signaling pathway plays a crucial role in long-term structural changes that underlie synaptic plasticity in hippocampus-dependent learning and memory processes impaired in Eif4e-bp1/2 double knockout (DKO) mice subjected to chronic stress and contextual aversive memory. As already proved, the midbrain tectum is known as a key midbrain region for defensive responses during threatening situations. Unconditioned fear-related responses organized by deep layers of the superior colliculus (cpCS) and periaqueductal gray matter (PAG) neurons regulated by inhibitory GABAergic nigrotectal pathways. The globus pallidus (GP), a basal nuclei structure rich in cannabinoid receptor type 1 (CB1), sends disinhibitory projections to the ventral midbrain. This work aims to investigate the role of the cannabinoid type 1 (CB1) receptors in male mice submitted to a depression-like and anxiety-related produced conditions in a dangerous situation, such as a predator cues (cat odor or exuvia from snakes) using a risk assessment (RA) test. Initially, the Eif4e-bp1/2-/--/-, Eif4e-bp1/2+/++/+ and C57BL/ 6 double knockout mutant mice will undergo chronic mild stress (CMS) model through the restraint stress (RS) test with a restriction of movement, and the chronic social defeat stress (CSDS) using a mouse of different strain and social group as a resident, followed by following behavioral assessments: Splash Test (ST) and Forced Swim Test (FST) to measure the depressive-like behaviors. On the experimental day 20 following 4 days of independent group of the same Eif4e-bp1/2-/--/-, mice and their wildtype littermates Eif4e-bp1/2+/++/+, will be pretreated with a single administration of URB597 (at 0.03, 0.3 and 3.0 mg/kg, i.p.) or vehicle and submitted the RA test.