Acute stress induces voluntary alcohol intake in mice through anxiety mitigated by toll-like receptor 4 antagonist

Abstract

Event Abstract Back to Event Acute stress induces voluntary alcohol intake in mice through anxiety mitigated by toll-like receptor 4 antagonist Huei G. Chuang1, Sangu Muthuraju1*, Nur Naznee H. Abd Aziz2, Mustapha Muzaimi2, Jafri M. Abdullah1, 2 and Zamzuri Idris1, 2 1 Hospital Universiti Sains Malaysia, Health Campus, Universiti Sains Malaysia, Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Malaysia 2 Universiti Sains Malaysia Health Campus, Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Malaysia Background Evidences previously supporting the functional involvement of toll-like receptor 4 (TLR4) in the mediation of neuroimmune system, further promoting the emergence of alcohol drinking behaviour following stress exposure. Thus, this study focused to investigate the effect of TLR4 antagonist Lipopolysaccharide-Rhodobacter Sphaeroides(LPS-RS) on the stress-induced voluntary alcohol drinking behaviour, neuronal component, and genes expression associating with stress and addiction. Methods This study involved the exposure of restraint and social isolation stress using Swiss Albino mice. Two-bottle choice ethanol exposure method was used in the evaluation of voluntary ethanol drinking behaviour. Several behavioural assessments including elevated plus-maze, light-dark box exploration, open field maze, beam walking test, and wire hanging test were carried out to assess the fear and anxiety-like behaviour, locomotion, motor coordination, and neuromuscular ability. Morphological and immunoreactivity analysis and genes expression analysis were done after the completion of behavioural assessments. Results TLR4 antagonist LPS-RS treated stressed-mice showed a significant decrease in the ethanol intake compared to stressed mice. Behaviourally, acute stress did not cause any significant deficits on the motor coordination, neuromuscular ability, locomotion, exploratory behaviour and risk-assessment behaviour. Behavioural results proved that acute stress exposure causing the emergence of fear and anxiety-like behaviour in the stressed mice. Morphological analysis showed no significant changes in prefrontal cortex and hippocampus among all groups, while in immunoreactivity analysis, stressed-mice showed a significant increase immunoreactivity of c-FOS in both prefrontal cortex and hippocampus, significant increase immunoreactivity of TLR4 in prefrontal cortex and GFAP in hippocampus. Stressed-mice too showed significant increase in the TLR4, NF-Kappa, iNOS, DRD2, CREB-1, and OPRM-1 genes expression compared to control and LPS-RS treated mice. Conclusion TLR4 suppression using antagonist LPS-RS could be effective in reducing the ethanol intake among stress-exposed mice suggested that TLR4 suppression might provide a therapeutic value in the treatment of stress-induced alcohol addiction. Acknowledgements We thank the School of Medical Sciences, Pusat Pengajian Sains Perubatan (PPSP), Universiti Sains Malaysia. This work has been supported by project number 304/PPSP/61313158 from the Short-term Grant received by Dr. Sangu Muthuraju. Keywords: Toll-like recepter 4 (TLR4), acute stress, Addiction, Alcohol drinking behavior, Lipopolysaccharide-Rhodobacter Sphaeroides(LPS-RS) Conference: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019. Presentation Type: Oral Presentation Topic: Miscellaneous Citation: Chuang HG, Muthuraju S, Abd Aziz NH, Muzaimi M, Abdullah JM and Idris Z (2019). Acute stress induces voluntary alcohol intake in mice through anxiety mitigated by toll-like receptor 4 antagonist. Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”. doi: 10.3389/conf.fphar.2018.63.00073 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Sep 2018; Published Online: 17 Jan 2019. * Correspondence: Dr. Sangu Muthuraju, Hospital Universiti Sains Malaysia, Health Campus, Universiti Sains Malaysia, Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Kelantan Darul Naim, 16150, Malaysia, muthuraju67@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Huei G Chuang Sangu Muthuraju Nur Naznee H Abd Aziz Mustapha Muzaimi Jafri M Abdullah Zamzuri Idris Google Huei G Chuang Sangu Muthuraju Nur Naznee H Abd Aziz Mustapha Muzaimi Jafri M Abdullah Zamzuri Idris Google Scholar Huei G Chuang Sangu Muthuraju Nur Naznee H Abd Aziz Mustapha Muzaimi Jafri M Abdullah Zamzuri Idris PubMed Huei G Chuang Sangu Muthuraju Nur Naznee H Abd Aziz Mustapha Muzaimi Jafri M Abdullah Zamzuri Idris Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.