Author(s): Ajeet Pal Singh, Ashish Kumar Sharma, Thakur Gurjeet Singh

Email(s): ,

DOI: 10.52711/0974-360X.2023.00405   

Address: Ajeet Pal Singh1,2*, Ashish Kumar Sharma1, Thakur Gurjeet Singh3
1NIMS Institute of Pharmacy, NIMS University, Jaipur - 303121, Rajasthan, India.
2St Soldier Insititue of Pharmacy, Jalandhar - 144011, Punjab, India.
3Chitkara College of Pharmacy, Chitkara University, Punjab, 140401, India.
*Corresponding Author E-mail:

Published In:   Volume - 16,      Issue - 5,     Year - 2023

Upregulation of nuclear factor kappa B plays a prominent role in drug addiction. The current study explored the neuroprotective effect of BAY 11-7085, a selective nuclear factor kappa B inhibitor, on the spontaneous alcohol withdrawal syndrome in mouse model of alcohol addiction. Administration of Alcohol (2g/kg, 10%, v/v, oral), once daily for 7 days. Assessment of behavioral parameters and exploratory parameters was done on 7 day after 8 hr. of the last ethanol administration for a period of 120 minutes. Various behavioural parameters were conducted like wall climbing test, composite withdrawal severity score, anxiety like behaviour assessed in open field and elevated plus test. Treatment with BAY 11-7085 markedly and dose dependently (p<0.05) attenuated spontaneous alcohol withdrawal syndrome in mice measured in terms of withdrawal severity score, wall climbing, locomotor sensitization by open field test and anxiety. Thus, it is suggested that activation of nuclear factor kappa B pathway is involved in the development of alcohol dependence induced withdrawal syndrome. Modulation of NFK-ß may be used as therapeutic agent to overcome the problems related with alcohol dependence.

Cite this article:
Ajeet Pal Singh, Ashish Kumar Sharma, Thakur Gurjeet Singh. BAY 11-7085 attenuates alcohol dependence induced spontaneous withdrawal syndrome in mice. Research Journal of Pharmacy and Technology 2023; 16(5):2458-4. doi: 10.52711/0974-360X.2023.00405

Ajeet Pal Singh, Ashish Kumar Sharma, Thakur Gurjeet Singh. BAY 11-7085 attenuates alcohol dependence induced spontaneous withdrawal syndrome in mice. Research Journal of Pharmacy and Technology 2023; 16(5):2458-4. doi: 10.52711/0974-360X.2023.00405   Available on:

1.    Singh TG, Rehni AK, Arora SK. Pharmacological modulation of farnesyltransferase subtype I attenuates mecamylamine-precipitated nicotine withdrawal syndrome in mice. Behavioural Pharmacology. 2013;24(8):668-677. doi:10.1097/FBP.0000000000000009
2.    Rehni AK, Singh TG, Arora S. SU-6656, a selective Src kinase inhibitor, attenuates mecamylamine-precipitated nicotine withdrawal syndrome in mice. Nicotine and Tobacco Research. 2012;14(4):407-414. doi:10.1093/ntr/ntr228
3.    Singh TG, Rehni AK, Arora S. Ro 32-0432 attenuates mecamylamine-precipitated nicotine withdrawal syndrome in mice. Naunyn-Schmiedeberg's Archives of Pharmacology 2013;386(3):197-204. doi:10.1007/s00210-012-0825-0
4.    Priyadarshini, Saraswathi K.N., Sheela Williams. A Study to assess the Quality of life of clients with Alcohol dependence syndrome attending and not attending Alcoholic Anonymous group meeting in selected Alcoholic Anonymous group and in rural areas of Mysore and with a view to develop self instructional module. Asian J. Nur. Edu. and Research 2014; 4(3): 298-303..
5.    Gupta A, Khan H, Kaur A, Singh TG. Novel Targets Explored in the Treatment of Alcohol Withdrawal Syndrome.  CNS and Neurological Disorders-Drug Targets. 2021;20(2):158-173. doi:10.2174/1871527319999201118155721
6.    Heilig M, Koob GF. A key role for corticotropin-releasing factor in alcohol dependence. Tendencias Neurosci. 2007;30(8):399-406. doi:10.1016/j.tins.2007.06.006
7.    Muniyandi S. Effectiveness of Pranayama on Anxiety among Alcoholics in a Selected De-addiction Centre at Chennai. Int. J. Nur. Edu. and Research. 2015; 3(3):299-309.
8.    Bruijnzeel AW, Zislis G, Wilson C, Gold MS. Antagonism of CRF receptors prevents the deficit in brain reward function associated with precipitated nicotine withdrawal in rats. Neuropsychopharmacology. 2007;32(4):955-963. doi:10.1038/sj.npp.1301192
9.    Bruijnzeel AW, Gold MS. The role of corticotropin-releasing factor-like peptides in cannabis, nicotine, and alcohol dependence. Brain research reviews. 2005;49(3):505-528. doi:10.1016/j.brainresrev.2005.01.007
10.    Koob GF, Le Moal M. Review. Neurobiological mechanisms for opponent motivational processes in addiction. Philosophical Transactions of the Royal Society B: Biological Sciences. 2008;363(1507):3113-3123. doi:10.1098/rstb.2008.0094
11.    Kaur G, Sharma S. A Descriptive Study to Assess the Internet Addiction and its Impact on Psychosocial Health among Adolescents. Int. J. Nur. Edu. and Research. 2019; 7(2):195-199.
12.    Ruby B, Benson MK, Kumar EP, Sudha S.Wilking JE. Evaluation of Ashwagandha in alcohol withdrawal syndrome. Asian Pacific Journal of Tropical Disease. 2012, S856-S860.1-6.
13.    Sharma M, Nagori K, Agrawal S, Verma VS, Swarnakar H, Vaishnav S, Nazir M, Khan N, Singh A. Drug Abuse: A Curse for Human Society. Asian Journal of Research in Pharmaceutical Sciences. 2014;4(2):99-109.
14.    Edenberg HJ, Xuei X, Wetherill LF, Bierut L, Bucholz K, Dick DM, Hesselbrock V, Kuperman S, Porjesz B, Schuckit MA, Tischfield JA. Association of NFKB1, which encodes a subunit of the transcription factor NF-kappaB, with alcohol dependence. Human molecular genetics. 2008;17(7):963-970. doi:10.1093/hmg/ddm368.
15.    Cui R, Li R, Guo X, Jia X, Yan M. RNA interference against stromal interacting molecule-1 (STIM1) ameliorates ethanol-induced hepatotoxicity. Chemico-Biological Interactions. 2018;289:47-56. doi:10.1016/j.cbi.2018.04.025
16.    Rehni AK, Bhateja P, Singh TG, Singh N. Nuclear factor-kappa-B inhibitor modulates the development of opioid dependence in a mouse model of naloxone-induced opioid withdrawal syndrome. Behavioural pharmacology 2008;19(3):265-269. doi:10.1097/FBP.0b013e3282febcd9
17.    Ökvist A, Johansson S, Kuzmin A, Bazov I, Merino-Martinez R, Ponomarev I, Mayfield RD, Harris RA, Sheedy D, Garrick T, Harper C. Neuroadaptations in human chronic alcoholics: dysregulation of the NF-kappa B system. PLoS One. 2007;2(9):e930. Published 2007 Sep 26. doi:10.1371/journal.pone.0000930
18.    Zou J, Crews F. Induction of innate immune gene expression cascades in brain slice cultures by ethanol: key role of NF-κB and proinflammatory cytokines. Alcoholism: Clinical and Experimental Research. 2010;34(5):777-789. doi:10.1111/j.1530-0277.2010.01150.x
19.    Zou J, Crews F. CREB and NF-kappa B transcription factors regulate sensitivity to excitotoxic and oxidative stress induced neuronal cell death. Cellular and molecular neurobiology 2006;26(4-6):385-405. doi:10.1007/s10571-006-9045-9
20.    Qin L, Crews FT. Chronic ethanol increases systemic TLR3 agonist-induced neuroinflammation and neurodegeneration. Journal of neuroinflammation. 2012; 9:130. doi:10.1186/1742-2094-9-130
21.    Naga Mallika A. V., Sushmitha M. Drug Abuse, Addiction, its Causes and Treatment. Res. J. Pharm. Dosage Form. and Tech. 2018; 10(4): 259-265.
22.    Truitt JM, Blednov YA, Benavidez JM, Black M, Ponomareva O, Law J, Merriman M, Horani S, Jameson K, Lasek AW, Harris RA. Inhibition of IKKβ Reduces Ethanol Consumption in C57BL/6J Mice. eNeuro. 2016;3(5):ENEURO.0256-16.2016. doi:10.1523/ENEURO.0256-16.2016
23.    Pierce JW, Schoenleber R, Jesmok G, Best J, Moore SA, Collins T, Gerritsen ME. Novel inhibitors of cytokine-induced IkappaB alpha phosphorylation and endothelial cell adhesion molecule expression show anti-inflammatory effects in vivo. Journal of Biological Chemistry. 1997;272(34):21096-21103. doi:10.1074/jbc.272.34.21096
24.    Masih J, Kumar D, Kumar S. An Analytical Study of the Epidemiological Profile of Alcoholics. Res. J. Pharmacology and Pharmacodynamics.2018; 10(3): 95-97.
25.    Karadayian AG, Busso MJ, Feleder C, Cutrera RA. Alterations in affective behavior during the time course of alcohol hangover. Behavioural brain research. 2013;253:128-138. doi:10.1016/j.bbr.2013.07.011
26.    Puspitasari AA, Ikawati Z, Swasthikawati S, Rahmawati A. Genotyping of Opioid Receptor Mu 1 (OPRM1) A118G Polymorphism in Indonesian Drug Addicts. Research Journal of Pharmacy and Technology. 2022; 15(2):799-6.
27.    Navarro JF, Burón E, Martín-López M. Anxiolytic-like activity of SB-205384 in the elevated plus-maze test in mice. Psicothema. 2006;18(1):100-104.
28.    Barua CC, Talukdar A, Begum SA, Borah P, Lahkar M. Anxiolytic activity of methanol leaf extract of Achyranthes aspera Linn in mice using experimental models of anxiety. Indian Journal of Pharmacology. 2012;44(1):63-67. doi:10.4103/0253-7613.91869
29.    Rehni AK, Singh TG. Pharmacological modulation of geranylgeranyltransferase and farnesyltransferase attenuates opioid withdrawal in vivo and in vitro. Neuropharmacology. 2013;71:19-26. doi:10.1016/j.neuropharm.2013.01.022
30.    Knapp DJ, Breese GR. Models of chronic alcohol exposure and dependence. Methods in Molecular Biology. 2012;829:205-230. doi:10.1007/978-1-61779-458-2_13
31.    Becker HC, Anton RF, Randall CL. Stereotypic wall climbing in mice during ethanol withdrawal: a new measure of physical dependence. Alcohol. 1987;4(6):443-447. doi:10.1016/0741-8329(87)90083-8
32.    Goldstein DB. Relationship of alcohol dose to intensity of withdrawal signs in mice. Journal of Pharmacology and Experimental Therapeutics. 1972;180(2):203-215.
33.    Goldstein DB. Alcohol withdrawal reactions in mice: effects of drugs that modify neurotransmission. Journal of Pharmacology and Experimental Therapeutics. 1973;186(1):1-9.
34.    Goldstein DB. Rates of onset and decay of alcohol physical dependence in mice. Journal of Pharmacology and Experimental Therapeutics. 1974;190(2):377-383.
35.    Qin L, He J, Hanes RN, Pluzarev O, Hong JS, Crews FT. Increased systemic and brain cytokine production and neuroinflammation by endotoxin following ethanol treatment. Journal of neuroinflammation. 2008;5:10. doi:10.1186/1742-2094-5-10
36.    Crews FT, Bechara R, Brown LA, Guidot DM, Mandrekar P, Oak S, Qin L, Szabo G, Wheeler M, Zou J. Cytokines and alcohol. Alcoholism: Clinical and Experimental Research. 2006;30(4):720-30.
37.    Wu PH, Coultrap S, Browning MD, Proctor WR. Correlated changes in NMDA receptor phosphorylation, functional activity, and sedation by chronic ethanol consumption. Journal of neurochemistry. 2010;115(5):1112-1122. doi:10.1111/j.1471-4159.2010.06991.x
38.    Montesinos J, Pascual M, Pla A, Maldonado C, Rodríguez-Arias M, Miñarro J, Guerri C. TLR4 elimination prevents synaptic and myelin alterations and long-term cognitive dysfunctions in adolescent mice with intermittent ethanol treatment. Brain, behavior, and immunity. 2015;45:233-244. doi:10.1016/j.bbi.2014.11.015
39.    Stephens DN, Duka T. Review. Cognitive and emotional consequences of binge drinking: role of amygdala and prefrontal cortex. Philosophical Transactions of the Royal Society B: Biological Sciences. 2008;363(1507):3169-3179. doi:10.1098/rstb.2008.0097
40.    Nestler EJ, Aghajanian GK. Molecular and cellular basis of addiction. Science. 1997;278(5335):58-63. doi:10.1126/science.278.5335.58
41.    Nennig SE, Schank JR. The Role of NFkB in Drug Addiction: Beyond Inflammation. Alcohol. 2017;52(2):172-179. doi:10.1093/alcalc/agw098
42.    Capasso A. Involvement of nuclear factor-kB in the expression of opiate withdrawal. Progress in neuro-psychopharmacology and biological psychiatry. 2001;25(6):1259-1268. doi:10.1016/s0278-5846(01)00178-6
43.    Sinha R, Li CS. Imaging stress- and cue-induced drug and alcohol craving: association with relapse and clinical implications. Drug and alcohol review. 2007;26(1):25-31. doi:10.1080/09595230601036960.
44.    Singh S, Singh TG, Dhiman S, Satija S, Gupta S. Pharmacological Evaluation Of Tinospora Cordifolia On Nicotine Dependence In Mice. Plant Archives. 2020;20(1):3757-62.
45.    Djordjevic J, Djordjevic A, Adzic M, Mitic M, Lukic I, Radojcic MB. Alterations in the Nrf2-Keap1 signaling pathway and its downstream target genes in rat brain under stress. Brain Research. 2015;1602:20-31. doi:10.1016/j.brainres.2015.01.010
46.    Zou H, Wang K, Gao Y, Song H, Xie Q, Jin M, Zhao G, Xiao H, Yu L. Chronic alcohol consumption from adolescence-to-adulthood in mice--hypothalamic gene expression changes in the dilated cardiomyopathy signaling pathway. BMC Neuroscience. 2014;15:61. doi:10.1186/1471-2202-15-61
47.    Gonzalez-Quintela A, Campos J, Loidi L, Quinteiro C, Perez LF, Gude F. Serum TNF-α levels in relation to alcohol consumption and common TNF gene polymorphisms. Alcohol, 2008;42(6), 513-518 DOI:10.1016/j.alcohol.2008.04.008
48.    Kong X, Yang Y, Ren L, Shao T, Li F, Zhao C, Liu L, Zhang H, McClain CJ, Feng W. Activation of autophagy attenuates EtOH-LPS-induced hepatic steatosis and injury through MD2 associated TLR4 signaling. Scientific reports. 2017;7(1):9292. doi:10.1038/s41598-017-09045-z

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