Putative Activation of the CB1 Cannabinoid Receptors Prevents Anxiety-Like Behavior, Oxidative Stress, and GABA Decrease in the Brain of Zebrafish Submitted to Acute Restraint Stress

Abstract

Anxiety disorder is a well-recognized condition observed in subjects submitted to acute stress. Although the brain mechanisms underlying this disorder remain unclear, the available evidence indicates that oxidative stress and GABAergic dysfunction mediate the generation of stress-induced anxiety. Cannabinoids are known to be efficient modulators of behavior, given that the activation of the cannabinoid receptors type-1 (CB1 receptors) induces anxiolytic-like effects in animal models. In the present study, we aimed to describe the effects of the stimulation of the CB1 receptors on anxiety-like behavior, oxidative stress, and the GABA content of the brains of zebrafish submitted to acute restraint stress (ARS). The animals submitted to the ARS protocol presented evident anxiety-like behavior with increased lipid peroxidation in the brain tissue. The evaluation of the levels of GABA in the zebrafish telencephalon presented decreased levels of GABA in the ARS group in comparison with the control. Treatment with ACEA, a specific CB1 receptor agonist, prevented ARS-induced anxiety-like behavior and oxidative stress in the zebrafish brain. ACEA treatment also prevented a decrease in GABA in the telencephalon of the animals submitted to the ARS protocol. Overall, these preclinical data strongly suggest that the CB1 receptors represent a potential target for the development of the treatment of anxiety disorders elicited by acute stress.

Acute clomipramine exposure elicits dose-dependent surfacing behavior in adult zebrafish (Danio rerio)

“…Thus, it appears that the 9-minute net stress protocol was not sufficient to elicit prototypic stress responses in the current study. Future studies examining the impact of clomipramine treatment on acute stress responses should use a more severe stressor, such as acute restraint stress ( Ghisleni et al, 2012 ; Lucas Luz et al, 2020 ), that consistently increases cortisol and alters top exploration in individual zebrafish. Alternatively, other physiological measures of stress could be used in future studies to compliment whole-body cortisol levels, such as brain levels of corticotropin-releasing hormone (CRH) mRNA ( Ghisleni et al, 2012 ) or c-fos levels ( Ariyasiri et al, 2021 ).…”

The relationship between serum levels of S‐100β and anxiety symptoms in patients with acute stroke

“…The increasing concentration of S‐100β might participate in nerve damage and apoptosis by activating an oxidative stress reaction 25 . Previous studies showed that oxidative stress was correlated with anxiety‐like behaviour after acute stress 26–28 . In addition, as a marker of the integrity of the blood–brain barrier, S‐100β has proved to be associated with blood–brain barrier damage 10 .…”

Oxytocin Signaling Acts as a Marker for Environmental Stressors in Zebrafish

“…In the present study, the axons of oxytocin neurons innervated the telencephalon and thalamus in adult zebrafish ( Figure 5 C,G, respectively). The telencephalon of fish is believed to be homologous to the mammalian limbic system, which controls anxiety, emotion, and motivation [ 77 ]. In zebrafish, the activation of cannabinoid receptor type-1 (CB1 receptor) in the telencephalon decreased anxiety from acute restraint stress [ 78 ].…”