The chronic pharmacological antagonism of the CB 1 receptor is not involved in the behavioral effects of antidepressants administered in mice submitted to chronic unpredictable stress

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 t...

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Bibliographic Details
Published in:Behavioural brain research 2023-07, Vol.450, p.114502
Main Authors: Ribeiro, Melissa A, Aguiar, Rafael P, Scarante, Franciele F, Fusse, Eduardo J, de Oliveira, Rúbia M W, Guimarães, Francisco S, Campos, Alline C
Format: Article
Language:English
Subjects:
Animals
Anti-Anxiety Agents - pharmacology
Antidepressive Agents - metabolism
Antidepressive Agents - pharmacology
Depression - drug therapy
Drug Inverse Agonism
Endocannabinoids - metabolism
Hippocampus - metabolism
Male
Mice
Receptor, Cannabinoid, CB1 - metabolism
Stress, Psychological - drug therapy
Stress, Psychological - metabolism
Venlafaxine Hydrochloride - pharmacology
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Summary: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 receptor 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 CB 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 CB receptor does not attenuate the antidepressant- or the anxiolytic-like effects of ESC nor VFX. ESC increased the expression of CB 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 CB receptors are not involved in behavioral and hippocampal neuroplastic effects observed after repeated antidepressant treatment in mice submitted to CUS.
ISSN:1872-7549