Lipopolysaccharide-induced depressive-like, anxiogenic-like and hyperalgesic behavior is attenuated by acute administration of α-(phenylselanyl) acetophenone in mice

• Published in: Neuropharmacology Vol. 146; pp. 128 - 137
• Main Authors: Sabedra Sousa, Fernanda Severo, Birmann, Paloma Taborda, Bampi, Suely Ribeiro, Fronza, Mariana G., Balaguez, Renata, Alves, Diego, Leite, Marlon Regis, Nogueira, Cristina Wayne, Brüning, César Augusto, Savegnago, Lucielli
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2019
• Subjects: Acetophenones - pharmacokinetics; Acetophenones - pharmacology; Animals; Anti-Anxiety Agents - pharmacology; Antidepressive Agents - pharmacology; Anxiety; Anxiety - chemically induced; Anxiety - drug therapy; Behavior, Animal - drug effects; Computer Simulation; Cyclooxygenase 2 - metabolism; Depression; Depression - chemically induced; Depression - drug therapy; Exploratory Behavior - drug effects; Hyperalgesia - chemically induced; Hyperalgesia - drug therapy; Lipopolysaccharides - pharmacology; Mice; Motor Activity - drug effects; Organoselenium Compounds - pharmacokinetics; Organoselenium Compounds - pharmacology; p38 Mitogen-Activated Protein Kinases - metabolism; Pain; Selenium; Synaptic signaling; Transcription Factor RelA - metabolism; Depression; Synaptic signaling; Anxiety; Pain; Selenium
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2018.11.028

The lipopolysaccharide (LPS) is an endotoxin derived from gram-negative bacteria, which induces inflammation. The aims of this study were to evaluate the possible α-(phenylselanyl) acetophenone (PSAP) activity in reducing comorbid hyperalgesia, depressive-like and anxiogenic-like symptoms induced by LPS in mice. In additional, investigated physical chemical properties of PSAP through in silico analysis by ADMET predictor software. The LPS (100 μg/kg, intraperitoneally) or saline were administered and after 4 h the treatment with PSAP (0.001–10 mg/kg, intragastric route [i.g.]) or FLX (10 mg/kg, i.g.) was performed, and after 30 min, the behavioral tests were carried out. LPS reduced the latency time for the first episode of immobility and increased the immobility time in the FST as well as decreased the grooming time in the splash test. PSAP reversed these alterations demonstrating an antidepressive-like effect. LPS also enhances the anxiogenic behavior in the elevated plus maze test (EPM). PSAP reversed these parameters, showing anxiolytic-like effect. LPS also decreased the latency time (s) on the hot plate and the treatment with PSAP at all doses significantly reversed the hyperalgesic effect of LPS. LPS increased the activation of p38MAPK and p-p65NF-κB pathways as well as the COX-2 levels in the cerebral cortex, which are indicative of an inflammatory response. Besides, it also reduced the levels of mBDNF, involved in neuroplasticity. Treatment with PSAP restored all these neurochemical alterations induced by LPS. The results demonstrated that PSAP presents antidepressive-like, anxiolytic-like and anti-hyperalgesic effects related to reduction in neuroinflammation. [Display omitted] •PSAP has anti-hyperalgesic effect.•PSAP has antidepressive-like activity.•PSAP has anxyolitic-like activity.