TY - JOUR
T1 - Role of toll-like receptor 4 antagonist Lipopolysaccharide-Rhodobacter sphaeroides on acute stress-induced voluntary ethanol preference and drinking behaviour
T2 - In vivo Swiss Albino mouse model
AU - Chuang, Huei Gau
AU - Aziz, Nur Naznee Hirni Abd
AU - Wong, Jia Hui
AU - Mustapha, Muzaimi
AU - Abdullah, Jafri Malin
AU - Idris, Zamzuri
AU - Abdullah, Zuraidah
AU - Alrafiah, Aziza
AU - Muthuraju, Sangu
N1 - Funding Information:
This work has been supported by project number 304/PPSP/61313158 from the Short-term Grant received by Dr. Sangu Muthuraju from Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia.
Funding Information:
We thank the School of Medical Sciences, Pusat Pengajian Sains Perubatan (PPSP), and Universiti Sains Malaysia. This work has been supported by project number 304/PPSP/61313158 from the Short-term Grant received by Dr. Sangu Muthuraju. Also, we thank hospital Universiti Sains Malaysia for providing the space to perform experiments. We thank Mr. Ajith Kumar, Journalist for English editing of this manuscript.
Publisher Copyright:
© 2020 Elsevier B.V. and ECNP
PY - 2021/4
Y1 - 2021/4
N2 - The present study focused on investigating the effect of toll-like receptor 4 (TLR4) antagonist Lipopolysaccharide-Rhodobacter sphaeroides (LPS-RS) on acute, stress-induced voluntary ethanol preference and drinking behaviour, neuronal components activation, and gene expression associated with stress and addictive behaviour. This study involved the exposure of restraint stress and social isolation using Swiss Albino mice. Two-bottle choice ethanol preference analysis was used in the evaluation of voluntary ethanol seeking and drinking behaviour. Several behavioural assessments were carried out to assess fear and anxiety-like behaviour, neuromuscular ability, motor coordination and locomotion. Morphological and immunoreactivity analysis and gene expression analysis were done after the completion of behavioural assessments. TLR4 antagonist LPS-RS treated stressed-mice showed a significant decrease in ethanol drinking compared with stressed mice. Behavioural results showed that stress exposure induced fear and anxiety-like behaviour; however; no significant deficit was found on motor coordination, neuromuscular ability, locomotion and exploratory behaviour among groups. Morphological analysis showed no significant change in the prefrontal cortex and hippocampus among all groups, while immunoreactivity analysis showed higher expression of c-Fos in prefrontal cortex and hippocampus, higher TLR4 expression in the prefrontal cortex and glial fibrillary acidic protein (GFAP) in hippocampus among stressed-animals. Stressed-mice also showed significant increase in TLR4, Nuclear Factor-Kappa B (NF-kB), inducible nitric oxide synthase (iNOS), dopamine receptor D2 (DRD2), cyclic adenosine monophosphate (cAMP) response element binding protein-1 (CREB-1) and opioid receptor MU-1 (OPRM-1) genes expression compared with control and LPS-RS treated stressed-mice. As a conclusion, the antagonism of TLR4 could provide therapeutic value in the treatment of stress-induced addiction.
AB - The present study focused on investigating the effect of toll-like receptor 4 (TLR4) antagonist Lipopolysaccharide-Rhodobacter sphaeroides (LPS-RS) on acute, stress-induced voluntary ethanol preference and drinking behaviour, neuronal components activation, and gene expression associated with stress and addictive behaviour. This study involved the exposure of restraint stress and social isolation using Swiss Albino mice. Two-bottle choice ethanol preference analysis was used in the evaluation of voluntary ethanol seeking and drinking behaviour. Several behavioural assessments were carried out to assess fear and anxiety-like behaviour, neuromuscular ability, motor coordination and locomotion. Morphological and immunoreactivity analysis and gene expression analysis were done after the completion of behavioural assessments. TLR4 antagonist LPS-RS treated stressed-mice showed a significant decrease in ethanol drinking compared with stressed mice. Behavioural results showed that stress exposure induced fear and anxiety-like behaviour; however; no significant deficit was found on motor coordination, neuromuscular ability, locomotion and exploratory behaviour among groups. Morphological analysis showed no significant change in the prefrontal cortex and hippocampus among all groups, while immunoreactivity analysis showed higher expression of c-Fos in prefrontal cortex and hippocampus, higher TLR4 expression in the prefrontal cortex and glial fibrillary acidic protein (GFAP) in hippocampus among stressed-animals. Stressed-mice also showed significant increase in TLR4, Nuclear Factor-Kappa B (NF-kB), inducible nitric oxide synthase (iNOS), dopamine receptor D2 (DRD2), cyclic adenosine monophosphate (cAMP) response element binding protein-1 (CREB-1) and opioid receptor MU-1 (OPRM-1) genes expression compared with control and LPS-RS treated stressed-mice. As a conclusion, the antagonism of TLR4 could provide therapeutic value in the treatment of stress-induced addiction.
KW - Acute stress
KW - Drinking behaviour
KW - Prefrontal cortex
KW - Toll-like receptor 4
KW - Voluntary alcohol seeking
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UR - http://www.scopus.com/inward/citedby.url?scp=85078845514&partnerID=8YFLogxK
U2 - 10.1016/j.euroneuro.2019.12.121
DO - 10.1016/j.euroneuro.2019.12.121
M3 - Article
C2 - 32014377
AN - SCOPUS:85078845514
SN - 0924-977X
VL - 45
SP - 59
EP - 72
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
ER -