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Protective effects of alpha-lipoic acid on anxiety-like behavior, memory and prevention of hippocampal oxidative stress in methamphetamine-treated rats

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Abstract

Rationale

Alpha-lipoic acid is an essential cofactor for aerobic metabolism and acts as a potent antioxidant in the body. It has been shown that acute exposure to methamphetamine induces oxidative stress, which is responsible for severe cognitive deficits in animals. The hippocampus plays a crucial role in the processing of memory and anxiety-like behavior.

Objectives

In this study, preventive effect of the alpha-lipoic acid on memory impairment in methamphetamine-induced neurotoxicity was investigated.

Methods

Wistar male rats (200–220 g) were allocated to five groups (seven rats in each group): (1) saline + saline, (2) saline + vehicle (sunflower oil as alpha-lipoic acid solvent), (3) methamphetamine + vehicle, (4) methamphetamine + alpha-lipoic acid 10 mg/kg, and (5) methamphetamine + alpha-lipoic acid 40 mg/kg. Rats received intraperitoneal methamphetamine repeatedly (2 × 20 mg/kg, 2 h interval). Alpha-lipoic acid was injected 30 min, 24 h, and 48 h after the last injection of methamphetamine. The passive avoidance test and open field were used for evaluation of memory retrieval and anxiety, respectively. After behavioral test, rats were anesthetized, their brains were extracted, and after preparing hippocampal homogenates, malondialdehyde (MDA) level, catalase, and superoxide dismutase (SOD) activities were evaluated.

Results

Statistical analysis showed that injection of saline or sunflower oil had no significant effect on anxiety, memory, or oxidative stress markers. Methamphetamine induced memory impairment, increased anxiety-like behavior and MDA level, but it reduced catalase and SOD activity. Treatment with alpha-lipoic acid decreased MDA, increased catalase and SOD activity, and also prevented memory impairment and anxiety-like behavior. Our results showed that alpha-lipoic acid protected the hippocampus from oxidative stress by elevating SOD and CAT activities and reduced memory impairment following acute methamphetamine injection. These findings suggest that alpha-lipoic acid may have a protective effect against the adverse effects of methamphetamine exposure on the hippocampus. Therefore, the current data indicated that ALA can reduce oxidative stress predominantly by its antioxidant property.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  • Agathos E, Tentolouris A (2018) Effect of α-lipoic acid on symptoms and quality of life in patients with painful diabetic neuropathy. 46(5):1779–1790

  • Anderson KL, Itzhak Y (2006) Methamphetamine-induced selective dopaminergic neurotoxicity is accompanied by an increase in striatal nitrate in the mouse. Ann N Y Acad Sci 1074:225–233

    Article  CAS  PubMed  Google Scholar 

  • Atchison ML, Perry RP (1987) The role of the κ enhancer and its binding factor NF-κB in the developmental regulation of κ gene transcription. Cell 48(1):121–128

    Article  CAS  PubMed  Google Scholar 

  • Attia AA, El-Twessy MY, Ghoneam HE, Hammed NS (2013) Histopathological and immunohistochemical studies on the role of α-lipoic acid on cyclophosphamide-induced immunosuppressive effect in mice. Delta J Sci 36(2):85–105

    Article  Google Scholar 

  • Avchalumov Y, Mandyam CD (2021) Plasticity in the hippocampus, neurogenesis and drugs of abuse 11(3):404

  • Babiuch K, Kuśnierz-Cabala B, Kęsek B, Okoń K, Darczuk D, Chomyszyn-Gajewska M (2020) Evaluation of proinflammatory, NF-kappaB dependent cytokines: IL-1α, IL-6, IL-8, and TNF-α in tissue specimens and saliva of patients with oral squamous cell carcinoma and oral potentially malignant disorders. J Clin Med 9(3):867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baradhi KM, Pathireddy S, Bose S, Aeddula NR (2019) Methamphetamine (N-methylamphetamine)-induced renal disease: underevaluated cause of end-stage renal disease (ESRD). BMJ Case Rep CP 12(9):e230288

    Article  Google Scholar 

  • Beauchamp C, Fridovich I (1971) Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. Anal Biochem 44(1):276–287

    Article  CAS  PubMed  Google Scholar 

  • Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O (2012) Oxidative stress and antioxidant defense. World Allergy Organ J 5(1):9–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boccia MM, Blake MG, Acosta GB, Baratti CM (2006) Post-retrieval effects of icv infusions of hemicholinium in mice are dependent on the age of the original memory. Learn Mem 13(3):376–381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  • Cadet JL, Brannock C (1998) Invited review free radicals and the pathobiology of brain dopamine systems. Neurochem Int 32(2):117–131

    Article  CAS  PubMed  Google Scholar 

  • Cadet JL, Krasnova IN, Jayanthi S, Lyles J (2007) Neurotoxicity of substituted amphetamines: molecular and cellular mechanisms. Neurotox Res 11(3):183–202

    Article  CAS  PubMed  Google Scholar 

  • Casciato P, Ambrosi N, Caro F, Vazquez M, Müllen E, Gadano A, de Santibañes E, de Santibañes M, Zandomeni M, Chahdi M et al (2018) α-Lipoic acid reduces postreperfusion syndrome in human liver transplantation - a pilot study. Transpl Int 31(12):1357–1368

    Article  CAS  PubMed  Google Scholar 

  • Cassagnes L-E, Chhour M, Pério P, Sudor J, Gayon R, Ferry G, Boutin JA, Nepveu F, Reybier K (2018) Oxidative stress and neurodegeneration: the possible contribution of quinone reductase 2. Free Radical Biol Med 120:56–61

    Article  CAS  Google Scholar 

  • Čechová B, Šlamberová R (2021) Methamphetamine, neurotransmitters and neurodevelopment. Physiol Res 70(Suppl 3):S301

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen L, Gu YJ, Zhang XG, Cheng L, Zhou MY, Yang Y, Wang Y (2023) Macrophage microvesicle-derived circ_YTHDF2 in methamphetamine-induced chronic lung injury

  • Cominski TP, Jiao X, Catuzzi JE, Stewart AL, Pang KC (2014) The role of the hippocampus in avoidance learning and anxiety vulnerability. Front Behav Neurosci 8:273

    Article  PubMed  PubMed Central  Google Scholar 

  • Costantino M, Guaraldi C, Costantino D (2016) Resolution of subchorionic hematoma and symptoms of threatened miscarriage using vaginal alpha lipoic acid or progesterone: clinical evidences. Eur Rev Med Pharmacol Sci 20(8):1656–1663

    CAS  PubMed  Google Scholar 

  • Dati LM, Ulrich H, Real CC, Feng ZP, Sun HS, Britto LR (2017) Carvacrol promotes neuroprotection in the mouse hemiparkinsonian model. Neuroscience 356:176–181

    Article  CAS  PubMed  Google Scholar 

  • Davis DL, Metzger DB, Vann PH, Wong JM, Shetty RA, Forster MJ, Sumien N (2023) Effects of chronic methamphetamine exposure on rewarding behavior and neurodegeneration markers in adult mice. Psychopharmacology (Berl) 240(6):1343–1358

  • Dixit S, Mehra RD, Dhar P (2020) Effect of α-lipoic acid on spatial memory and structural integrity of developing hippocampal neurons in rats subjected to sodium arsenite exposure. Environ Toxicol Pharmacol 75:103323

    Article  CAS  PubMed  Google Scholar 

  • Eger GA, Ferreira VV, Batista CR, Bonde H, Lima DDd, Wyse AT, Cruz JNd, Rodrigues AF, Magro DDD, da Cruz JG (2016) Antioxidant effect of simvastatin throught oxidative imbalance caused by lisdexamfetamine dimesylate. An Acad Bras Ciênc 88(1):335–348

    Article  CAS  PubMed  Google Scholar 

  • Ekthuwapranee K, Sotthibundhu A, Govitrapong P (2015) Melatonin attenuates methamphetamine-induced inhibition of proliferation of adult rat hippocampal progenitor cells in vitro. J Pineal Res 58(4):418–428

    Article  CAS  PubMed  Google Scholar 

  • Etaee F, Asadbegi M, Taslimi Z, Shahidi S, Sarihi A, Soleimani Asl S, Komaki A (2017) The effects of methamphetamine and buprenorphine, and their interaction on anxiety-like behavior and locomotion in male rats. Neurosci Lett 655:172–178

    Article  CAS  PubMed  Google Scholar 

  • Fallahi S, Babri S, Farajdokht F, Ghiasi R, Soltani Zangbar H, Karimi P, Mohaddes G (2019) Neuroprotective effect of ghrelin in methamphetamine-treated male rats. Neurosci Lett 707:134304

    Article  PubMed  Google Scholar 

  • Fathi-Moghaddam H, Kesmati M, Kargar HM (2006) The effect of paragigantocellularis lateralis lesion on conditioned place preference (CPP) in presence or absence of alpha2 adrenergic agonist (clonidine) in male rats. Acta Physiol Hung 93(1):33–40

    Article  CAS  PubMed  Google Scholar 

  • Fayez AM, Zakaria S, Moustafa D (2018) Alpha lipoic acid exerts antioxidant effect via Nrf2/HO-1 pathway activation and suppresses hepatic stellate cells activation induced by methotrexate in rats. Biomed Pharmacother 105:428–433

    Article  CAS  PubMed  Google Scholar 

  • Fedoce ADG, Ferreira F, Bota RG, Bonet-Costa V, Sun PY (2018) The role of oxidative stress in anxiety disorder: cause or consequence? Free Radic Res 52(7):737–750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fulton S, Pissios P, Manchon RP, Stiles L, Frank L, Pothos EN, Maratos-Flier E, Flier JS (2006) Leptin regulation of the mesoaccumbens dopamine pathway. Neuron 51(6):811–822

    Article  CAS  PubMed  Google Scholar 

  • Gębka A, Serkies-Minuth E (2014) Effect of the administration of alpha-lipoic acid on contrast sensitivity in patients with type 1 and type 2 diabetes. 2014:131538

  • Ghadiri A, Etemad L, Moshiri M, Moallem SA, Jafarian AH, Hadizadeh F, Seifi M (2017) Exploring the effect of intravenous lipid emulsion in acute methamphetamine toxicity. Iran J Basic Med Sci 20(2):138–144

    PubMed  PubMed Central  Google Scholar 

  • Ghasemi M, Navidhamidi M, Rezaei F, Azizikia A, Mehranfard N (2022) Anxiety and hippocampal neuronal activity: relationship and potential mechanisms. Cogn Affect Behav Neurosci 22(3):431–449

    Article  PubMed  Google Scholar 

  • Ghibu S, Richard C, Vergely C, Zeller M, Cottin Y, Rochette L (2009) Antioxidant properties of an endogenous thiol: alpha-lipoic acid, useful in the prevention of cardiovascular diseases. J Cardiovasc Pharmacol 54(5):391–398

    Article  CAS  PubMed  Google Scholar 

  • Gholami M, Hozuri F, Abdolkarimi S, Mahmoudi M, Motaghinejad M, Safari S, Sadr S (2021) Pharmacological and molecular evidence of neuroprotective curcumin effects against biochemical and behavioral sequels caused by methamphetamine: possible function of CREB-BDNF signaling pathway. Basic Clin Neurosci 12(3):325–338

    CAS  PubMed  PubMed Central  Google Scholar 

  • Giannopolitis CN, Ries SK (1977) Superoxide dismutases: I. Occurrence in higher plants. Plant Physiol 59(2):309–314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Glasner-Edwards S, Mooney LJ (2014) Methamphetamine psychosis: epidemiology and management. CNS Drugs 28(12):1115–1126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Golsorkhdan SA, Boroujeni ME, Aliaghaei A, Abdollahifar MA, Ramezanpour A, Nejatbakhsh R, Anarkooli IJ, Barfi E, Fridoni MJ (2020) Methamphetamine administration impairs behavior, memory and underlying signaling pathways in the hippocampus. Behav Brain Res 379:112300

    Article  CAS  PubMed  Google Scholar 

  • Guo Y, Jones D, Palmer JL, Forman A, Dakhil SR, Velasco MR, Weiss M, Gilman P, Mills GM, Noga SJ et al (2014) Oral alpha-lipoic acid to prevent chemotherapy-induced peripheral neuropathy: a randomized, double-blind, placebo-controlled trial. Support Care Cancer: off J Multinatl Assoc Support Care Cancer 22(5):1223–1231

    Article  Google Scholar 

  • Hager K, Kenklies M, McAfoose J, Engel J, Münch G (2007) Alpha-lipoic acid as a new treatment option for Alzheimer’s disease–a 48 months follow-up analysis. J Neural Transm Suppl 72:189–193

    CAS  Google Scholar 

  • Hakimi Z, Salmani H, Marefati N, Arab Z, Gholamnezhad Z, Beheshti F, Shafei MN, Hosseini M (2020) Protective effects of carvacrol on brain tissue inflammation and oxidative stress as well as learning and memory in lipopolysaccharide-challenged rats. Neurotox Res 37(4):965–976

    Article  CAS  PubMed  Google Scholar 

  • Halpin LE, Collins SA, Yamamoto BK (2014) Neurotoxicity of methamphetamine and 3, 4-methylenedioxymethamphetamine. Life Sci 97(1):37–44

    Article  CAS  PubMed  Google Scholar 

  • Hosseinzadeh S, Dabidi Roshan V, Pourasghar M (2013) Effects of intermittent aerobic training on passive avoidance test (shuttle box) and stress markers in the dorsal hippocampus of wistar rats exposed to administration of homocysteine. Iran J Psychiatry Behav Sci 7(1):37–44

    PubMed  PubMed Central  Google Scholar 

  • Jamali S, Dezfouli MP, Kalbasi A (2023) Selective modulation of hippocampal theta oscillations in response to morphine versus natural reward. Brain Sci 13(2):322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jayanthi S, Ladenheim B, Cadet JL (1998) Methamphetamine-induced changes in antioxidant enzymes and lipid peroxidation in copper/zinc-superoxide dismutase transgenic mice. Ann N Y Acad Sci 844:92–102

    Article  CAS  PubMed  Google Scholar 

  • Kaur D, Behl T, Sehgal A, Singh S, Sharma N, Chigurupati S, Alhowail A, Abdeen A, Ibrahim SF, Vargas-De-La-Cruz C et al (2021) Decrypting the potential role of α-lipoic acid in Alzheimer’s disease. Life Sci 284:119899

    Article  CAS  PubMed  Google Scholar 

  • Khalil A, Kovac S, Morris G, Walker MC (2017) Carvacrol after status epilepticus (SE) prevents recurrent SE, early seizures, cell death, and cognitive decline. Epilepsia 58(2):263–273

    Article  CAS  PubMed  Google Scholar 

  • Krasnova IN, Cadet JL (2009) Methamphetamine toxicity and messengers of death. Brain Res Rev 60(2):379–407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krasnova IN, Hodges AB, Ladenheim B, Rhoades R, Phillip CG, Cesena A, Ivanova E, Hohmann CF, Cadet JL (2009) Methamphetamine treatment causes delayed decrease in novelty-induced locomotor activity in mice. Neurosci Res 65(2):160–165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87(1):99–163

    Article  CAS  PubMed  Google Scholar 

  • Kutlu MG, Gould TJ (2016) Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction. Learn Mem 23(10):515–533 (Cold Spring Harbor, NY)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Y, Schellhorn HE (2007) Rapid kinetic microassay for catalase activity. J Biomol Techn: JBT 18(4):185

    Google Scholar 

  • Li YH, He Q, Yu JZ, Liu CY, Feng L, Chai Z, Wang Q, Zhang HZ, Zhang GX, Xiao BG et al (2015) Lipoic acid protects dopaminergic neurons in LPS-induced Parkinson’s disease model. Metab Brain Dis 30(5):1217–1226

    Article  PubMed  Google Scholar 

  • Lingappan K (2018) NF-κB in oxidative stress. Current Opinion in Toxicology 7:81–86

    Article  PubMed  Google Scholar 

  • Liu L, Cao J, Chen J, Zhang X, Wu Z, Xiang H (2016) Effects of peptides from Phascolosoma esculenta on spatial learning and memory via anti-oxidative character in mice. Neurosci Lett 631:30–35

    Article  CAS  PubMed  Google Scholar 

  • Loy BD, Fling BW, Horak FB, Bourdette DN, Spain RI (2018) Effects of lipoic acid on walking performance, gait, and balance in secondary progressive multiple sclerosis. Complement Ther Med 41:169–174

    Article  PubMed  PubMed Central  Google Scholar 

  • Mahboob A, Farhat SM, Iqbal G, Babar MM, Zaidi NU, Nabavi SM, Ahmed T (2016) Alpha-lipoic acid-mediated activation of muscarinic receptors improves hippocampus- and amygdala-dependent memory. Brain Res Bull 122:19–28

    Article  CAS  PubMed  Google Scholar 

  • Martens U, Wree A (2001) Distribution of [3H]MK-801, [3H]AMPA and [3H]Kainate binding sites in rat hippocampal long-term slice cultures isolated from external afferents. Anat Embryol 203(6):491–500

    Article  CAS  Google Scholar 

  • Melo P, Zanon-Moreno V, Alves CJ, Magalhães A, Tavares MA, Pinazo-Duran MD, Moradas-Ferreira P (2010) Oxidative stress response in the adult rat retina and plasma after repeated administration of methamphetamine. Neurochem Int 56(3):431–436

    Article  CAS  PubMed  Google Scholar 

  • Mortazavi A, Mohammad Pour Kargar H, Beheshti F, Anaeigoudari A, Vaezi G, Hosseini M (2021) The effects of carvacrol on oxidative stress, inflammation, and liver function indicators in a systemic inflammation model induced by lipopolysaccharide in rats. Int J Vitam Nutr Res 93(2):111–121

    Article  PubMed  Google Scholar 

  • Moszczynska A, Callan SP (2017) Molecular, behavioral, and physiological consequences of methamphetamine neurotoxicity: implications for treatment. J Pharmacol Exp Ther 362(3):474–488

    Article  CAS  PubMed  Google Scholar 

  • Nazari A, Hojjat SK, Moghadam AJ, Khalili MN, Akbari H, Khorrami M, Sherafati J, Akbarzadeh M, Farimani ZB, Kaviyani F (2023) The survey of prevalence and content of hallucinations and delusions in methamphetamine dependents. Int J High Risk Behav Addict 12(2):e134015

    Article  Google Scholar 

  • Ngkelo A, Meja K, Yeadon M, Adcock I, Kirkham PA (2012) LPS induced inflammatory responses in human peripheral blood mononuclear cells is mediated through NOX4 and Giα dependent PI-3kinase signalling. J Inflamm 9(1):1 (London, England)

    Article  CAS  Google Scholar 

  • Nordahl TE, Salo R, Leamon M (2003) Neuropsychological effects of chronic methamphetamine use on neurotransmitters and cognition: a review. J Neuropsychiatry Clin Neurosci 15(3):317–325

    Article  CAS  PubMed  Google Scholar 

  • Ohkawa H, Ohishi N, Yagi K (1978) Reaction of linoleic acid hydroperoxide with thiobarbituric acid. J Lipid Res 19(8):1053–1057

    Article  CAS  PubMed  Google Scholar 

  • Ohmori T, Koyama T, Muraki A, Yamashita I (1993) Competitive and noncompetitive N-methyl-D-aspartate antagonists protect dopaminergic and serotonergic neurotoxicity produced by methamphetamine in various brain regions. J Neural Transm Gen Sect 92(2–3):97–106

    Article  CAS  PubMed  Google Scholar 

  • Okesina A, Ajenikoko M, Mohammed A, Omoola O, Buhari M (2022) Progesterone mitigates trimethyltin-induced hippocampal damage through oxidative stress biomarkers. Trop J Health Sci 29(2):27–31

    Google Scholar 

  • Ortman HA, Newby ML, Acevedo J, Siegel JA (2021) The acute effects of multiple doses of methamphetamine on locomotor activity and anxiety-like behavior in adolescent and adult mice. Behav Brain Res 405:113186

    Article  CAS  PubMed  Google Scholar 

  • Padmalayam I, Hasham S, Saxena U, Pillarisetti S (2009) Lipoic acid synthase (LASY): a novel role in inflammation, mitochondrial function, and insulin resistance. Diabetes 58(3):600–608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perera J, Tan JH, Jeevathayaparan S, Chakravarthi S, Haleagrahara N (2011) Neuroprotective effects of alpha lipoic acid on haloperidol-induced oxidative stress in the rat brain. Cell Biosci 1(1):1–6

    Article  Google Scholar 

  • Prentice H, Modi JP, Wu J-Y (2015) Mechanisms of neuronal protection against excitotoxicity, endoplasmic reticulum stress, and mitochondrial dysfunction in stroke and neurodegenerative diseases. Oxid Med Cell Longev v.2015

  • Reed LJ (2001) A trail of research from lipoic acid to α-keto acid dehydrogenase complexes. J Biol Chem 276(42):38329–38336

    Article  CAS  PubMed  Google Scholar 

  • Rezaie M, Nasehi M, Vaseghi S, Mohammadi-Mahdiabadi-Hasani MH, Zarrindast MR, Nasiri Khalili MA (2020) The protective effect of alpha lipoic acid (ALA) on social interaction memory, but not passive avoidance in sleep-deprived rats. Naunyn-Schmiedeberg’s Arch Pharmacol 393(11):2081–2091

    Article  CAS  Google Scholar 

  • Richards JR, Laurin EG (2023) Methamphetamine toxicity. StatPearls Publishing Bookshelf ID: NBK430895

  • Rocher C, Gardier AM (2001) Effects of repeated systemic administration of d-fenfluramine on serotonin and glutamate release in rat ventral hippocampus: comparison with methamphetamine using in vivo microdialysis. Naunyn-Schmiedeberg’s Arch Pharmacol 363(4):422–428

    Article  CAS  Google Scholar 

  • Roohbakhsh A, Moshiri M, Salehi Kakhki A, Iranshahy M, Amin F, Etemad L (2021) Thymoquinone abrogates methamphetamine-induced striatal neurotoxicity and hyperlocomotor activity in mice. Res Pharma Sci 16(4):391–399

    Article  Google Scholar 

  • Salehi B, Berkay Yılmaz Y, Antika G, Boyunegmez Tumer T (2019) Insights on the use of α-lipoic acid for therapeutic purposes. Biomolecules 9(8):356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Samarghandian S, Farkhondeh T, Samini F, Borji A (2016) Protective effects of carvacrol against oxidative stress induced by chronic stress in rat’s brain, liver, and kidney. Biochem Res Int 2016:2645237

    Article  PubMed  PubMed Central  Google Scholar 

  • Sanadgol N, Golab F, Askari H, Moradi F, Ajdary M, Mehdizadeh M (2018) Alpha-lipoic acid mitigates toxic-induced demyelination in the corpus callosum by lessening of oxidative stress and stimulation of polydendrocytes proliferation. Metab Brain Dis 33(1):27–37

    Article  CAS  PubMed  Google Scholar 

  • Sancheti H, Akopian G, Yin F, Brinton RD, Walsh JP, Cadenas E (2013) Age-dependent modulation of synaptic plasticity and insulin mimetic effect of lipoic acid on a mouse model of Alzheimer’s disease. PLoS ONE 8(7):e69830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanders LLO, de Souza Menezes CE, Chaves Filho AJM, de Almeida VG, Fechine FV, Rodrigues de Queiroz MG, da Cruz G, Fonseca S, Mendes Vasconcelos SM, Amaral de Moraes ME, Gama CS et al (2017) α-Lipoic acid as adjunctive treatment for schizophrenia: an open-label trial. J Clin Psychopharmacol 37(6):697–701

    Article  CAS  PubMed  Google Scholar 

  • Scott JC, Woods SP, Matt GE, Meyer RA, Heaton RK, Atkinson JH, Grant I (2007) Neurocognitive effects of methamphetamine: a critical review and meta-analysis. Neuropsychol Rev 17(3):275–297

    Article  PubMed  Google Scholar 

  • Shafahi M, Vaezi G, Shajiee H, Sharafi S, Khaksari M (2018) Crocin inhibits apoptosis and astrogliosis of hippocampus neurons against methamphetamine neurotoxicity via antioxidant and anti-inflammatory mechanisms. Neurochem Res 43(12):2252–2259

    Article  CAS  PubMed  Google Scholar 

  • Sharma DR, Wani WY, Sunkaria A, Kandimalla RJ, Verma D, Cameotra SS, Gill KD (2013) Quercetin protects against chronic aluminum-induced oxidative stress and ensuing biochemical, cholinergic, and neurobehavioral impairments in rats. Neurotox Res 23(4):336–357

    CAS  PubMed  Google Scholar 

  • Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM (2009) Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta (BBA)-Gen Subj 1790(10):1149–1160.

  • Shin E-J, Tran H-Q, Nguyen P-T, Jeong JH, Nah S-Y, Jang C-G, Nabeshima T, Kim H-C (2018) Role of mitochondria in methamphetamine-induced dopaminergic neurotoxicity: involvement in oxidative stress, neuroinflammation, and pro-apoptosis—a review. Neurochem Res 43(1):66–78

    Article  PubMed  Google Scholar 

  • Siedlak SL, Casadesus G, Webber KM, Pappolla MA, Atwood CS, Smith MA, Perry G (2009) Chronic antioxidant therapy reduces oxidative stress in a mouse model of Alzheimer’s disease. Free Radical Res 43(2):156–164

    Article  CAS  Google Scholar 

  • Silva MCC, de Sousa CNS, Gomes PXL, de Oliveira GV, Araújo FYR, Ximenes NC, da Silva JC, Vasconcelos GS, Leal LKAM, Macêdo D (2016) Evidence for protective effect of lipoic acid and desvenlafaxine on oxidative stress in a model depression in mice. Prog Neuropsychopharmacol Biol Psychiatry 64:142–148

    Article  CAS  PubMed  Google Scholar 

  • Stoll S, Hartmann H, Cohen SA, Müller WE (1993) The potent free radical scavenger alpha-lipoic acid improves memory in aged mice: putative relationship to NMDA receptor deficits. Pharmacol Biochem Behav 46(4):799–805

    Article  CAS  PubMed  Google Scholar 

  • Struntz KH, Siegel JA (2018) Effects of methamphetamine exposure on anxiety-like behavior in the open field test, corticosterone, and hippocampal tyrosine hydroxylase in adolescent and adult mice. Behav Brain Res 348:211–218

    Article  CAS  PubMed  Google Scholar 

  • Swant J, Chirwa S, Stanwood G, Khoshbouei H (2010) Methamphetamine reduces LTP and increases baseline synaptic transmission in the CA1 region of mouse hippocampus. PLoS ONE 5(6):e11382

    Article  PubMed  PubMed Central  Google Scholar 

  • Thompson PM, Hayashi KM, Simon SL, Geaga JA, Hong MS, Sui Y, Lee JY, Toga AW, Ling W, London ED (2004) Structural abnormalities in the brains of human subjects who use methamphetamine. J Neurosci: off J Soc Neurosci 24(26):6028–6036

    Article  CAS  Google Scholar 

  • Tobolski J, Sawyer DB, Song SJ, Afari ME (2022) Cardiovascular disease associated with methamphetamine use: a review. Heart Fail Rev 27(6):2059–2065

  • Tomar A, McHugh TJ (2022) The impact of stress on the hippocampal spatial code. Trends Neurosci 45(2):120–132

    Article  CAS  PubMed  Google Scholar 

  • Wallace TL, Gudelsky GA, Vorhees CV (1999) Methamphetamine-induced neurotoxicity alters locomotor activity, stereotypic behavior, and stimulated dopamine release in the rat. J Neurosci: off J Soc Neurosci 19(20):9141–9148

    Article  CAS  Google Scholar 

  • Yamada T, Hashida K, Takarada-Iemata M, Matsugo S, Hori O (2011) α-Lipoic acid (LA) enantiomers protect SH-SY5Y cells against glutathione depletion. Neurochem Int 59(7):1003–1009

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto Y, Yamamoto K, Hayase T, Abiru H, Shiota K, Mori C (2002) Methamphetamine induces apoptosis in seminiferous tubules in male mice testis. Toxicol Appl Pharmacol 178(3):155–160

    Article  CAS  PubMed  Google Scholar 

  • Yamamotová A, Šlamberová R (2012) Behavioral and antinociceptive effects of different psychostimulant drugs in prenatally methamphetamine-exposed rats. Physiol Res 61(Suppl 2):S139-147

    Article  PubMed  Google Scholar 

  • Yang L, Wen Y, Lv G, Lin Y, Tang J, Lu J, Zhang M, Liu W, Sun X (2017) α-Lipoic acid inhibits human lung cancer cell proliferation through Grb2-mediated EGFR downregulation. Biochem Biophys Res Commun 494(1–2):325–331

    Article  CAS  PubMed  Google Scholar 

  • Yang X, Wang Y, Li Q, Zhong Y, Chen L, Du Y, He J, Liao L, Xiong K, Yi C-x (2018) The main molecular mechanisms underlying methamphetamine-induced neurotoxicity and implications for pharmacological treatment. Front Mol Neurosci 11:186

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang S, Jin Y, Liu X, Yang L, Ge Z, Wang H, Li J, Zheng J (2014) Methamphetamine modulates glutamatergic synaptic transmission in rat primary cultured hippocampal neurons. Brain Res 1582:1–11

    Article  CAS  PubMed  Google Scholar 

  • Zhang W-J, Frei B (2001) α-Lipoic acid inhibits TNF-a-induced NF-κB activation and adhesion molecule expression in human aortic endothelial cells. FASEB J 15(13):2423–2432

    Article  CAS  PubMed  Google Scholar 

  • Ziegler D, Nowak H, Kempler P, Vargha P, Low PA (2004) Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a meta-analysis. Diabet Med: J Br Diabet Assoc 21(2):114–121

    Article  CAS  Google Scholar 

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Funding

This work was supported by Islamic Azad University, Damghan Branch, Iran (grant 14560).

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Authors and Affiliations

  1. Department of Biology, Islamic Azad University, Damghan, Iran

    Hossein Mohammad Pour Kargar & Hamid Noshiri

  2. Faculty of Pharmacy, Islamic Azad University, Damghan Branch, Damghan, Iran

    Hossein Mohammad Pour Kargar

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  1. Hossein Mohammad Pour Kargar
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  2. Hamid Noshiri
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All authors contributed in all process of the research and writing of the manuscript.

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Correspondence to Hossein Mohammad Pour Kargar.

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Ethical approval

Rats received humane care according to the criteria outlined in the Guide for the Care and Use of Laboratory Animals (National Institute of Health Publication No. 80-23, revised 1996) and Helsinki Declaration (1964 and its later amendments). All protocols were approved by the Ethics Committee of Islamic Azad University, Shahrood Branch (IR.IAU.SHAHROOD.REC.1400.064).

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Kargar, H.M.P., Noshiri, H. Protective effects of alpha-lipoic acid on anxiety-like behavior, memory and prevention of hippocampal oxidative stress in methamphetamine-treated rats. Psychopharmacology 241, 315–326 (2024). https://doi.org/10.1007/s00213-023-06487-4

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