The chronic pharmacological antagonism of the CB1 receptor is not involved in the behavioral effects of antidepressants administered in mice submitted to chronic unpredictable stress

Author(s)

Ribeiro, Melissa A. ; Aguiar, Rafael P. ; Scarante, Franciele F. ; Fusse, Eduardo J. ; de Oliveira, Rubia M. W. ; Guimara, Francisco S. ; Campos, Alline C.

• Document type: Journal article
• Source: Behavioural Brain Research; v. 450, p. 10-pg., 2023-05-23.

Abstract

Several pieces of evidence suggest that the monoaminergic theory of depression cannot fully explain all behavioral and neuroplastic changes observed after antidepressant chronic treatment. Other molecular targets, such as the endocannabinoid system, have been associated with the chronic effects of these drugs. In the present study, we hypothesized that the behavioral and neuroplastic effects observed after repeated treatment with the antidepressants (AD) Escitalopram (ESC) or venlafaxine (VFX) in chronically stressed mice depend on CB1 re-ceptor activation. Male mice submitted to the chronic unpredictable stress (CUS) paradigm for 21 days were treated with Esc (10 mg/kg) or VFX (20 mg/kg) once a day in the presence or not of AM251 (0.3 mg/kg), a CB1 receptor antagonist/inverse agonist. At the end of the CUS paradigm, we conducted behavior tests to evaluate depressive-and anxiety-like behaviors. Our results demonstrated that chronic blockade of the CB1 receptor does not attenuate the antidepressant-or the anxiolytic-like effects of ESC nor VFX. ESC increased the expression of CB1 in the hippocampus, but AM251 did not change the pro-proliferative effects of ESC in the dentate gyrus or the increased expression of synaptophysin induced by this AD in the hippocampus. Our results suggest that CB1 receptors are not involved in behavioral and hippocampal neuroplastic effects observed after repeated antide-pressant treatment in mice submitted to CUS. (AU)

• FAPESP's process: 19/09178-3 - Involvement of endocannabinoid signaling and neuroplasticity within the prefrontal cortex in the behavioral effects of the combination cannabidiol and escitalpram in stressed mice
• Grantee: Franciele Franco Scarante
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/05551-0 - Investigation of the involvement of endocannabinoid system on behavioral and plastic effects of antidepressant drugs
• Grantee: Alline Cristina de Campos
• Support Opportunities: Research Grants - Young Investigators Grants