Acute Restraint Stress Evokes Anxiety-Like Behavior Mediated by Telencephalic Inactivation and GabAergic Dysfunction in Zebrafish Brains

Abstract

Acute stress is an important factor in the development of anxiety disorders. Zebrafish are an organism model widely used by studies that aim to describe the events in the brain that control stress-elicited anxiety. the goal of the current study was to evaluate the pattern of cell activation in the telencephalon of adult zebrafish and the role of the GABAergic system on the modulation of anxiety-like behavior evoked by acute restraint stress. Zebrafish that underwent acute restraint stress presented decreased expression of the c-fos protein in their telencephalon as well as a significant decrease in GABA release. The data also supports that decreased GABA levels in zebrafish brains have diminished the activation of GABAA receptors eliciting anxiety-like behavior. Taken together these findings have helped clarify a neurochemical pathway controlling anxiety-like behavior evoked by acute stress in zebrafish while also opening the possibility of new perspective opportunities to use zebrafish as an animal model to test anxyolitic drugs that target the GABAergic system. open Scientific RepoRtS | (2020) 10:5551 | https://doi.

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

“…A total of 156 adult-long-fin zebrafish ( Danio rerio ) of both sexes (50:50 ratio) were purchased from a local distributor, in Ananindeua, Pará (Brazil). These animals were kept for at least one week in 50 L tanks (50 cm × 35 cm × 30 cm) under appropriate conditions, as described by Assad et al ( 2020 ), that is, at 27 ± 2°C, pH = 6.5, and a 14/10 h light/dark cycle, with a density of one animal per liter, fed twice a day. The tanks were maintained under constant mechanical and chemical filtration.…”

“…Zebrafish were cold-anesthetized and injected intra-abdominally with either saline solution (SAL, 0.9%) or 1 mg/Kg ACEA dissolved in 0.005% DMSO. Drug dilution and treatments were performed 30 min before the behavioral experiments to assure drug distribution and reach in zebrafish brain as performed by de Carvalho et al ( 2019 ) and Assad et al ( 2020 ). The fish were then transferred to individual plastic aquaria, in which they were kept for 30 min.…”

“…The effects of CB1 stimulation on oxidative injuries also remain unclear, although treatment with AEA has been shown to reduce the production of Reactive Oxygen Species (ROS) and protect hippocampal neurons against oxidative injury (Lipina and Hundal, 2016 ; Gallelli et al, 2018 ). Our research group has recently demonstrated that Acute Restraint Stress (ARS) induces anxiety-like behavior, associated with GABAergic dysfunction in the zebrafish brain (Assad et al, 2020 ), and based on these findings; the present study evaluated the preventive effects of treatment with the CB1 agonist on the neurochemistry of anxiety-like behavior induced by ARS in zebrafish.…”

“…The World Health Organization (WHO) estimates that approximately one-third of the world’s population develops anxiety at some time, with many of the cases being triggered by traumatic events (Bandelow and Michaelis, 2015 ). Acute stress is an important source of anxiety disorder in humans and several studies have correlated this event with imbalances in the brain neurotransmitter systems such as the serotoninergic, glutamatergic, and GABAergic systems (Gemikonakli et al, 2019 ; Assad et al, 2020 ; de Abreu et al, 2020a ; Feder et al, 2020 ). There is good evidence that the pharmacological modulation of the GABAergic system can prevent the anxiety-like behavior induced by acute and chronic stress (Nuss, 2015 ; Assad et al, 2020 ; Farajdokht et al, 2020 ).…”

“…Acute stress is an important source of anxiety disorder in humans and several studies have correlated this event with imbalances in the brain neurotransmitter systems such as the serotoninergic, glutamatergic, and GABAergic systems (Gemikonakli et al, 2019 ; Assad et al, 2020 ; de Abreu et al, 2020a ; Feder et al, 2020 ). There is good evidence that the pharmacological modulation of the GABAergic system can prevent the anxiety-like behavior induced by acute and chronic stress (Nuss, 2015 ; Assad et al, 2020 ; Farajdokht et al, 2020 ). Pro-oxidant events in the brain tissue are also known to be closely associated with anxiety disorder elicited by post-traumatic events (Sousa et al, 2018 ).…”