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Aripiprazole mitigates lipopolysaccharide-induced memory impairments in rats

Year 2024, Volume: 28 Issue: 4, 1022 - 1032, 28.06.2025

Vasudevan Mani Bander Shehail Alshammeri

Abstract

Aripiprazole (APZ) is an atypical class of antipsychotics prescribed to patients with schizophrenia, bipolar disorder, and treatment-resistant depression. Preclinical and clinical research have shown that APZ is helpful for cognitive performance in people with schizophrenia who exhibit negative symptoms. An endotoxin extract from gram- negative bacteria lipopolysaccharide (LPS) was reported to induce memory deficits and used as a model for explaining Alzheimer’s disease (AD). This research aimed to determine that APZ could mitigate cognitive deficits with LPS-induced neurotoxicity in rats. Two doses of APZ (1 or 2 mg/kg) were administrated orally for 28 days to groups of rats. Four doses (1 mg/kg) of LPS were injected peripherally to induce neurotoxic. The cognitive characteristics were tested using the Y-maze and the elevated plus maze (EPM). In order to assess the levels of acetylcholine (ACh), the brain tissues were collected. The results highlighted that the transfer latency (TL) time in EPM was prolonged after LPS induction and also it reduced the novel arm performance of the Y-maze test. The APZ administration reduced the TL in EPM and improved the number of novel arm entries and also it extended the animals’ time spent in the novel arm. Further, the higher dose of APZ (2 mg/kg, p.o.) improved the cholinergic activities in the brain by increasing the ACh levels after LPS induction. These results are suggested that APZ is one of the therapeutic avenues for cognitive deficits related to schizophrenia and other neuroinflammatory-related neurodegenerative insults.

Keywords

Aripiprazole Neurodegeneration Dementia Elevated plus-maze Y-Maze Acetylcholine

References

  • [1] Gale SA, Acar D, Daffner KR. Dementia. Am J Med. 2018; 131(10): 1161-1169. https://doi.org/10.1016/j.amjmed.2018.01.022
  • [2] Aarsland D. Epidemiology and pathophysiology of dementia-related psychosis. J Clin Psychiatry. 2020; 81(5): AD19038BR1C. https://doi.org/10.4088/JCP.AD19038BR1C
  • [3] Ribe AR, Laursen TM, Charles M, Katon W, Fenger-Grøn M, Davydow D, Chwastiak L, Cerimele JM, Vestergaard M. Long-term risk of dementia in persons with schizophrenia: A Danish population-based cohort study. JAMA Psychiatry. 2015; 72(11): 1095-1101. https://doi.org/10.1001/jamapsychiatry.2015.1546
  • [4] Geda YE, Schneider LS, Gitlin LN, Miller DS, Smith GS, Bell J, Evans J, Lee M, Porsteinsson A, Lanctôt KL, Rosenberg PB, Sultzer DL, Francis PT, Brodaty H, Padala PP, Onyike CU, Ortiz LA, Ancoli-Israel S, Bliwise DL, Martin JL, Vitiello MV, Yaffe K, Zee PC, Herrmann N, Sweet RA, Ballard C, Khin NA, Alfaro C, Murray PS, Schultz S, Lyketsos CG. Neuropsychiatric symptoms in Alzheimer's disease: past progress and anticipation of the future. Alzheimers Dement. 2013; 9(5): 602-608. https://doi.org/10.1016/j.jalz.2012.12.001
  • [5] Cai L, Huang J. Schizophrenia and risk of dementia: a meta-analysis study. Neuropsychiatr Dis Treat. 2018; 14: 2047-2055. https://doi.org/10.2147/NDT.S172933
  • [6] Barch DM. The cognitive neuroscience of schizophrenia. Annu Rev Clin Psychol. 2005; 1: 321-353. https://doi.org/10.1146/annurev.clinpsy.1.102803.143959
  • [7] Cummings JL, Mega, M. Neuropsychiatry and behavioral neurology, Oxford University Press, New York, NY, USA 2003.
  • [8] Howes OD, Kapur S. The dopamine hypothesis of schizophrenia: version III--the final common pathway. Schizophr Bull. 2009; 35(3): 549-562. https://doi.org/10.1093/schbul/sbp006
  • [9] Keefe RS, Silva SG, Perkins DO, Lieberman JA. The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: A review and meta-analysis. Schizophr Bull. 1999; 25(2): 201-222. https://doi.org/10.1093/oxfordjournals.schbul.a033374
  • [10] Hou Y, Xie J, Yuan Y, Cheng Z, Han X, Yang L, Yu X, Shi C. Neurocognitive effects of atypical antipsychotics in patients with first-episode schizophrenia. Nord J Psychiatry. 2020; 74(8): 594-601. https://doi.org/10.1080/08039488.2020.1771767
  • [11] Vreeker A, van Bergen AH, Kahn RS. Cognitive enhancing agents in schizophrenia and bipolar disorder. Eur Neuropsychopharmacol. 2015; 25(7): 969-1002. https://doi.org/10.1016/j.euroneuro.2015.04.014
  • [12] Kikuchi T, Maeda K, Suzuki M, Hirose T, Futamura T, McQuade RD. Discovery research and development history of the dopamine D2 receptor partial agonists, aripiprazole and brexpiprazole. Neuropsychopharmacol Rep. 2021; 41(2): 134-143. https://doi.org/10.1002/npr2.12180
  • [13] Bartram LA, Lozano J, Coury, DL. Aripiprazole for treating irritability associated with autism spectrum disorders. Expert Opin Pharmacother. 2019; 20(12): 1421-1142. https://doi.org/10.1080/14656566.2019.1626825.
  • [14] Mani V, Arfeen M, Dhaked DK, Mohammed HA, Amirthalingam P, Elsisi HA. Neuroprotective effect of methanolic Ajwa seed extract on lipopolysaccharide-induced memory dysfunction and neuroinflammation: In vivo, molecular docking and dynamics studies. Plants (Basel). 2023; 12(4): 934. https://doi.org/10.3390/plants12040934.
  • [15] Mani V. Betahistine protects doxorubicin-induced memory deficits via cholinergic and anti-inflammatory pathways in mouse brain. Int J Pharmacol. 2021; 17: 584-595. https://scialert.net/abstract/?doi=ijp.2021.584.595.
  • [16] Lopez OL, Kuller LH. Epidemiology of aging and associated cognitive disorders: Prevalence and incidence of Alzheimer's disease and other dementias. Handb Clin Neurol. 2019; 167: 139-148. https://doi.org/10.1016/B978-0-12-804766-8.00009-1.
  • [17] Rajesh Y, Kanneganti TD. Innate immune cell death in neuroinflammation and Alzheimer's Disease. Cells. 2022; 11(12): 1885. https://doi.org/10.3390/cells11121885
  • [18] Zakaria R, Wan Yaacob WM, Othman Z, Long I, Ahmad AH, Al-Rahbi B. Lipopolysaccharide-induced memory impairment in rats: A model of Alzheimer's disease. Physiol Res. 2017; 66(4): 553-565. https://doi.org/10.33549/physiolres.933480
  • [19] Burda K, Czubak A, Kus K, Nowakowska E, Ratajczak P, Zin J. Influence of aripiprazole on the antidepressant, anxiolytic and cognitive functions of rats. Pharmacol Rep. 2011; 63(4): 898-907. https://doi.org/10.1016/s1734-1140(11)70605-3
  • [20] Peitl V, Štefanović M, Orlović I, Culej J, Rendulić A, Matešić K, Karlović D. Long acting aripiprazole influences cognitive functions in recent onset schizophrenia. Psychopharmacology (Berl). 2021; 238(6): 1563-1573. https://doi.org/10.1007/s00213-021-05788-w
  • [21] Banoub JH, El Aneed A, Cohen AM, Joly N. Structural investigation of bacterial lipopolysaccharides by mass spectrometry and tandem mass spectrometry. Mass Spectrom Rev. 2010; 29(4): 606-650. https://doi.org/10.1002/mas.20258
  • [22] Ganji A, Farahani I, Saeedifar AM, Mosayebi G, Ghazavi A, Majeed M, Jamialahmadi T, Sahebkar A. Protective effects of curcumin against lipopolysaccharide-induced toxicity. Curr Med Chem. 2021; 28(33): 6915-6930. https://doi.org/10.2174/0929867328666210525124707
  • [23] Hereta M, Kamińska K, Białoń M, Wąsik A, Lorenc-Koci E, Rogóż Z. Effect of combined treatment with aripiprazole and antidepressants on the MK-801-induced deficits in recognition memory in novel recognition test and on the release of monoamines in the rat frontal cortex. Behav Brain Res. 2020; 393: 112769. https://doi.org/10.1016/j.bbr.2020.112769
  • [24] Park SY, Kim HY, Lee YS, Heo HJ, Shin HK, Lee WS, Hong KW, Kim CD. Augmented improvement of cognition and memory by aripiprazole add-on for cilostazol treatment in the chronic cerebral hypoperfusion mouse model. Behav Brain Res. 2019; 365: 133-140. https://doi.org/10.1016/j.bbr.2019.03.013
  • [25] Nagai T, Murai R, Matsui K, Kamei H, Noda Y, Furukawa H, Nabeshima T. Aripiprazole ameliorates phencyclidine-induced impairment of recognition memory through dopamine D1 and serotonin 5-HT1A receptors. Psychopharmacology (Berl). 2009; 202(1-3): 315-328. https://doi.org/10.1007/s00213-008-1240-6
  • [26] Burda-Malarz K, Kus K, Ratajczak P, Czubak A, Hardyk S, Nowakowska, E. Evaluation of the antidepressant, anxiolytic and memory-improving efficacy of aripiprazole and fluoxetine in ethanol-treated rats. Drug Chem Toxicol. 2014; 37(3): 281-289. https://doi.org/10.3109/01480545.2013.851687
  • [27] Ratajczak P, Kus K, Murawiecka P, Słodzińska I, Zaprutko T, Kopciuch D, Paczkowska A, Nowakowska E. Memory deterioration based on the tobacco smoke exposure and methylazoxymethanol acetate administration vs. aripiprazole, olanzapine and enrichment environment conditions. Pharmacol Biochem Behav. 2020; 189: 172855. https://doi.org/10.1016/j.pbb.2020.172855
  • [28] Mani V, Arfeen M, Ali HM, Hafez Abdel-Moneim AM, Aldubayan M, Dhanasekaran M, Alhowail A. Ciproxifan attenuates the memory impairment induced by lipopolysaccharide through modulation of cholinergic transmission in the mouse brain. Eur Rev Med Pharmacol Sci. 2022; 26(6): 1897-1905. https://doi.org/10.26355/eurrev_202203_28335
  • [29] Tripathi A, Paliwal P, Krishnamurthy S. Piracetam attenuates LPS-induced neuroinflammation and cognitive impairment in rats. Cell Mol Neurobiol. 2017; 37(8): 1373-1386. https://doi.org/10.1007/s10571-017-0468-2.
  • [30] Poimenova A, Markaki E, Rahiotis C, Kitraki E. Corticosterone-regulated actions in the rat brain are affected by perinatal exposure to low dose of bisphenol A. Neuroscience. 2010; 167(3): 741-749. https://doi.org/10.1016/j.neuroscience.2010.02.051
  • [31] Kraeuter AK, Guest PC, Sarnyai Z. The Y-maze for assessment of spatial working and reference memory in mice. Methods Mol Biol. 2019; 1916: 105-111. https://doi.org/10.1007/978-1-4939-8994-2_10
  • [32] Gamage R, Wagnon I, Rossetti I, Childs R, Niedermayer G, Chesworth R, Gyengesi, E. Cholinergic modulation of glial function during aging and chronic neuroinflammation. Front Cell Neurosci. 2020; 14: 577912. https://doi.org/10.3389/fncel.2020.577912
  • [33] Abg Abd Wahab DY, Gau CH, Zakaria R, Muthu Karuppan MK, A-Rahbi BS, Abdullah Z, Alrafiah A, Abdullah JM, Muthuraju S. Review on cross talk between neurotransmitters and neuroinflammation in striatum and cerebellum in the mediation of motor behaviour. Biomed Res Int. 2019; 2019: 1767203. https://doi.org/10.1155/2019/1767203
  • [34] Houdek HM, Larson J, Watt JA, Rosenberger TA. Bacterial lipopolysaccharide induces a dose-dependent activation of neuroglia and loss of basal forebrain cholinergic cells in the rat brain. Inflamm Cell Signal. 2014; 1(1): e47. https://doi.org/10.14800%2Fics.47.
  • [35] Burzynski HE, Macht VA, Woodruff JL, Crawford JN, Erichsen JM, Piroli GG, Grillo CA, Fadel JR, Reagan LP. Pyridostigmine bromide elicits progressive and chronic impairments in the cholinergic anti-inflammatory pathway in the prefrontal cortex and hippocampus of male rats. Neurobiol Stress. 2022; 18: 100446. https://doi.org/10.1016/j.ynstr.2022.100446
  • [36] Sharma AC, Kulkarni SK. Evaluation of learning and memory mechanisms employing elevated plus-maze in rats and mice. Prog Neuropsychopharmacol Biol Psychiatry. 1992; 16(1): 117-125. https://doi.org/10.1016/0278-5846(92)90014-6
There are 36 citations in total.

Details

Primary Language English
Subjects Basic Pharmacology
Journal Section Articles
Authors

Vasudevan Mani 0000-0002-8440-8366

Bander Shehail Alshammeri 0000-0002-8539-3901

Publication Date June 28, 2025
Published in Issue Year 2024 Volume: 28 Issue: 4

Cite

APA Mani, V., & Alshammeri, B. S. (2025). Aripiprazole mitigates lipopolysaccharide-induced memory impairments in rats. Journal of Research in Pharmacy, 28(4), 1022-1032.
AMA Mani V, Alshammeri BS. Aripiprazole mitigates lipopolysaccharide-induced memory impairments in rats. J. Res. Pharm. July 2025;28(4):1022-1032.
Chicago Mani, Vasudevan, and Bander Shehail Alshammeri. “Aripiprazole Mitigates Lipopolysaccharide-Induced Memory Impairments in Rats”. Journal of Research in Pharmacy 28, no. 4 (July 2025): 1022-32.
EndNote Mani V, Alshammeri BS (July 1, 2025) Aripiprazole mitigates lipopolysaccharide-induced memory impairments in rats. Journal of Research in Pharmacy 28 4 1022–1032.
IEEE V. Mani and B. S. Alshammeri, “Aripiprazole mitigates lipopolysaccharide-induced memory impairments in rats”, J. Res. Pharm., vol. 28, no. 4, pp. 1022–1032, 2025.
ISNAD Mani, Vasudevan - Alshammeri, Bander Shehail. “Aripiprazole Mitigates Lipopolysaccharide-Induced Memory Impairments in Rats”. Journal of Research in Pharmacy 28/4 (July 2025), 1022-1032.
JAMA Mani V, Alshammeri BS. Aripiprazole mitigates lipopolysaccharide-induced memory impairments in rats. J. Res. Pharm. 2025;28:1022–1032.
MLA Mani, Vasudevan and Bander Shehail Alshammeri. “Aripiprazole Mitigates Lipopolysaccharide-Induced Memory Impairments in Rats”. Journal of Research in Pharmacy, vol. 28, no. 4, 2025, pp. 1022-3.
Vancouver Mani V, Alshammeri BS. Aripiprazole mitigates lipopolysaccharide-induced memory impairments in rats. J. Res. Pharm. 2025;28(4):1022-3.