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Oxidative stress and BDNF as possible markers for the severity of crack cocaine use in early withdrawal

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Abstract

Rationale

An important goal of addiction research is to discover neurobiological markers that could predict the severity of addiction and help to determine appropriate treatment. Brain-derived neurotrophic factor (BDNF) and thiobarbituric acid reactive substances (TBARS) are being related to cerebral plasticity and impairment caused by substance abuse.

Objectives

This study aims to evaluate alteration of TBARS and BDNF levels among crack cocaine users during early drug withdrawal and its relationship to severity of drug use.

Methods

Forty-nine adults crack cocaine users were recruited at a public psychiatric hospital with a specialized addiction treatment unit. Blood sample was collected at intake and discharge for the analysis of TBARS and BDNF measures. Information about drug use was assessed by the Addiction Severity Index 6th Version (ASI-6). Detailed information about crack cocaine use was obtained through the “Profile of the crack cocaine user.” Severity of crack use was estimated using information from age of first crack use, years of crack use, and crack rocks used in the previous 30 days.

Results

There is a positive correlation between TBARS levels and severity of crack cocaine use (R = 0.304, p = 0.04) and a negative correlation between BDNF and severity of crack cocaine use (R = −0.359, p = 0.01) at discharge. Also, we found an inverse correlation between TBARS and BDNF levels (R = −0.294, p = 0.004) at discharge.

Conclusions

Our findings suggest that BDNF and TBARS could be possible markers for the severity of drug use. Further studies may show how those markers could be related to staging, prognosis, and treatment in crack cocaine dependence.

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References

  • Andreazza AC, Kauer-Sant’anna M, Frey BN, Bond DJ, Kapczinski F, Young LT et al (2008) Oxidative stress markers in bipolar disorder: a meta-analysis. J Affect Disord 111(2–3):135–144

    Article  PubMed  CAS  Google Scholar 

  • Angelucci F, Ricci V, Pomponi M, Conte G, Mathé AA, Attilio Tonali P et al (2007) Chronic heroin and cocaine abuse is associated with decreased serum concentrations of the nerve growth factor and brain-derived neurotrophic factor. J Psychopharmacol 21(8):820–825

    Article  PubMed  CAS  Google Scholar 

  • Angelucci F, Ricci V, Martinotti G, Palladino I, Spalletta G, Caltagirone C et al (2010) Ecstasy (MDMA)-addicted subjects show increased serum levels of brain-derived neurotrophic factor, independently from a rise of drug-induced psychotic symptoms. Addict Biol 15(3):365–367

    Article  PubMed  CAS  Google Scholar 

  • Asevedo E, Gadelha A, Noto C, Mansur RB, Zugman A, Belangero SI et al (2013) Impact of peripheral levels of chemokines, BDNF and oxidative markers on cognition in individuals with schizophrenia. J Psychiatr Res 47(10):1376–1382

    Article  PubMed  Google Scholar 

  • Bartkowska K, Turlejski K, Djavadian RL (2010) Neurotrophins and their receptors in early development of the mammalian nervous system. Acta Neurobiol Exp (Wars) 70(4):454–467

    Google Scholar 

  • Calabrese V, Scapagnini G, Giuffrida Stella AM, Bates TE, Clark JB (2001) Mitochondrial involvement in brain function and dysfunction: relevance to aging, neurodegenerative disorders and longevity. Neurochem Res 26(6):739–764

    Article  PubMed  CAS  Google Scholar 

  • Castren E (2004) Neurotrophins as mediators of drug effects on mood, addiction, and neuroprotection. Mol Neurobiol 29(3):289–302

    Article  PubMed  CAS  Google Scholar 

  • Cerretani D, Fineschi V, Bello S, Riezzo I, Turillazzi E, Neri M (2012) Role of oxidative stress in cocaine-induced cardiotoxicity and cocaine-related death. Curr Med Chem 19(33):5619–5623

    Article  PubMed  CAS  Google Scholar 

  • Corominas M, Roncero C, Ribases M, Castells X, Casas M (2007) Brain-derived neurotrophic factor and its intracellular signaling pathways in cocaine addiction. Neuropsychobiology 55(1):2–13

    Article  PubMed  CAS  Google Scholar 

  • Corominas-Roso M, Roncero C, Eiroa-Orosa FJ, Gonzalvo B, Grau-Lopez L, Ribases M et al (2013) Brain-derived neurotrophic factor serum levels in cocaine-dependent patients during early abstinence. Eur Neuropsychopharmacol 23(9):1078–1084

    Article  PubMed  CAS  Google Scholar 

  • Costa MA, Girard M, Dalmay F, Malauzat D (2011) Brain-derived neurotrophic factor serum levels in alcohol-dependent subjects 6 months after alcohol withdrawal. Alcohol Clin Exp Res 35(11):1966–1973

    Article  PubMed  CAS  Google Scholar 

  • Davies KJ (1995) Oxidative stress: the paradox of aerobic life. Biochem Soc Symp 61:1–31

    PubMed  CAS  Google Scholar 

  • Dias AC, Vieira DL, Gomes LS, Araujo MR, Laranjeira R (2011) Longitudinal outcomes among a cohort of crack users after 12 years from treatment discharge. J Addict Dis 30(3):271–280

    Article  PubMed  Google Scholar 

  • D'Sa C, Fox HC, Hong AK, Dileone RJ, Sinha R (2011) Increased serum brain-derived neurotrophic factor is predictive of cocaine relapse outcomes: a prospective study. Biol Psychiatry 70(8):706–711

    Article  PubMed  PubMed Central  Google Scholar 

  • D'Sa C, Dileone RJ, Anderson GM, Sinha R (2012) Serum and plasma brain-derived neurotrophic factor (BDNF) in abstinent alcoholics and social drinkers. Alcohol 46(3):253–259

    Article  PubMed  PubMed Central  Google Scholar 

  • Duman RS, Monteggia LM (2006) A neurotrophic model for stress-related mood disorders. Biol Psychiatry 59(12):1116–1127

    Article  PubMed  CAS  Google Scholar 

  • Dvorakova M, Sivonova M, Trebaticka J, Skodacek I, Waczulikova I, Muchova J et al (2006) The effect of polyphenolic extract from pine bark, Pycnogenol on the level of glutathione in children suffering from attention deficit hyperactivity disorder (ADHD). Redox Rep 11(4):163–172

    Article  PubMed  Google Scholar 

  • Filomeni G, Ciriolo MR (2006) Redox control of apoptosis: an update. Antioxid Redox Signal 8(11–12):2187–2192

    Article  PubMed  CAS  Google Scholar 

  • Fukunaga K, Yoshida M, Nakazono N (1998) A simple, rapid, highly sensitive and reproducible quantification method for plasma malondialdehyde by high-performance liquid chromatography. Biomed Chromatogr 12(5):300–303

    Article  PubMed  CAS  Google Scholar 

  • Fumagalli F, Di Pasquale L, Caffino L, Racagni G, Riva MA (2007) Repeated exposure to cocaine differently modulates BDNF mRNA and protein levels in rat striatum and prefrontal cortex. Eur J Neurosci 26(10):2756–2763

    Article  PubMed  Google Scholar 

  • Fumagalli F, Moro F, Caffino L, Orrù A, Cassina C, Giannotti G et al (2013) Region-specific effects on BDNF expression after contingent or non-contingent cocaine i.v. self-administration in rats. Int J Neuropsychopharmacol 16(4):913–918

    Article  PubMed  CAS  Google Scholar 

  • Giannotti G, Caffino L, Calabrese F, Racagni G, Riva MA, Fumagalli F (2014) Prolonged abstinence from developmental cocaine exposure dysregulates BDNF and its signaling network in the medial prefrontal cortex of adult rats. Int J Neuropsychopharmacol 17(4):625–634

    Article  PubMed  CAS  Google Scholar 

  • Govitrapong P, Boontem P, Kooncumchoo P, Pinweha S, Namyen J, Sanvarinda Y et al (2009) Increased blood oxidative stress in amphetamine users. Addict Biol 15(1):100–102

    Article  Google Scholar 

  • Grimm JW, Lu L, Hayashi T, Hope BT, Su TP, Shaham Y (2003) Time-dependent increases in brain-derived neurotrophic factor protein levels within the mesolimbic dopamine system after withdrawal from cocaine: implications for incubation of cocaine craving. J Neurosci 23(3):742–747

    PubMed  CAS  Google Scholar 

  • Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97(6):1634–1658

    Article  PubMed  CAS  Google Scholar 

  • Hamid A (1992) The developmental cycle of a drug epidemic: the cocaine smoking epidemic of 1981-1991. J Psychoactive Drugs 24(4):337–348

    Article  PubMed  CAS  Google Scholar 

  • Hauck S, Gomes F, Silveira Júnior EM, Almeida E, Possa M, Ceitlin LH (2009) Serum levels of brain-derived neurotrophic factor in acute and posttraumatic stress disorder: a case report study. Rev Bras Psiquiatr 31(1):48–51

    Article  PubMed  Google Scholar 

  • Hauck S, Kapczinski F, Roesler R, de Moura SE, Magalhães PV, Kruel LR et al (2010) Serum brain-derived neurotrophic factor in patients with trauma psychopathology. Prog Neuropsychopharmacol Biol Psychiatry 34(3):459–462

    Article  PubMed  CAS  Google Scholar 

  • Heberlein A, Muschler M, Wilhelm J, Frieling H, Lenz B, Groschl M et al (2010) BDNF and GDNF serum levels in alcohol-dependent patients during withdrawal. Prog Neuropsychopharmacol Biol Psychiatry 34(6):1060–1064

    Article  PubMed  CAS  Google Scholar 

  • Heberlein A, Muschler M, Frieling H, Lenz B, Wilhelm J, Gröschl M et al (2011) Decreased galanin serum levels are associated with alcohol-craving during withdrawal. Prog Neuropsychopharmacol Biol Psychiatry 35(2):568–572

    Article  PubMed  CAS  Google Scholar 

  • Henskens R, Garretsen H, Bongers I, Van Dijk A, Sturmans F (2008) Effectiveness of an outreach treatment program for inner city crack abusers: compliance, outcome, and client satisfaction. Subst Use Misuse 43(10):1464–1475

    Article  PubMed  Google Scholar 

  • Huang MC, Chen CH, Liu SC, Ho CJ, Shen WW, Leu SJ (2008) Alterations of serum brain-derived neurotrophic factor levels in early alcohol withdrawal. Alcohol Alcohol 43(3):241–245

    Article  PubMed  CAS  Google Scholar 

  • Huang MC, Chen CC, Peng FC, Tang SH, Chen CH (2009a) The correlation between early alcohol withdrawal severity and oxidative stress in patients with alcohol dependence. Prog Neuropsychopharmacol Biol Psychiatry 33(1):66–69

    Article  PubMed  CAS  Google Scholar 

  • Huang MC, Chen CH, Peng FC, Tang SH, Chen CC (2009b) Alterations in oxidative stress status during early alcohol withdrawal in alcoholic patients. J Formos Med Assoc 108(7):560–569

    Article  PubMed  Google Scholar 

  • Kapczinski F, Vieta E, Andreazza AC, Frey BN, Gomes FA, Tramontina J et al (2008) Allostatic load in bipolar disorder: implications for pathophysiology and treatment. Neurosci Biobehav Rev 32(4):675–692

    Article  PubMed  Google Scholar 

  • Kapczinski F, Dal-Pizzol F, Teixeira AL, Magalhaes PV, Kauer-Sant'Anna M, Klamt F et al (2010) A systemic toxicity index developed to assess peripheral changes in mood episodes. Mol Psychiatry 15(8):784–786

    Article  PubMed  CAS  Google Scholar 

  • Kessler F, Cacciola J, Alterman A, Faller S, Souza-Formigoni ML, Cruz MS et al (2012) Psychometric properties of the sixth version of the Addiction Severity Index (ASI-6) in Brazil. Rev Bras Psiquiatr 34(1):24–33

    Article  PubMed  Google Scholar 

  • Kim DJ, Roh S, Kim Y, Yoon SJ, Lee HK, Han CS et al (2005) High concentrations of plasma brain-derived neurotrophic factor in methamphetamine users. Neurosci Lett 388(2):112–115

    Article  PubMed  CAS  Google Scholar 

  • Kovacic P (2005) Unifying mechanism for addiction and toxicity of abused drugs with application to dopamine and glutamate mediators: electron transfer and reactive oxygen species. Med Hypotheses 65(1):90–96

    Article  PubMed  CAS  Google Scholar 

  • Kovacic P, Cooksy AL (2005) Unifying mechanism for toxicity and addiction by abused drugs: electron transfer and reactive oxygen species. Med Hypotheses 64(2):357–366

    Article  PubMed  CAS  Google Scholar 

  • Kuloglu M, Atmaca M, Tezcan E, Gecici O, Tunckol H, Ustundag B (2002) Antioxidant enzyme activities and malondialdehyde levels in patients with obsessive-compulsive disorder. Neuropsychobiology 46(1):27–32

    Article  PubMed  CAS  Google Scholar 

  • Lee BC, Choi IG, Kim YK, Ham BJ, Yang BH, Roh S et al (2009) Relation between plasma brain-derived neurotrophic factor and nerve growth factor in the male patients with alcohol dependence. Alcohol 43(4):265–269

    Article  PubMed  Google Scholar 

  • Li X, DeJoseph MR, Urban JH, Bahi A, Dreyer JL, Meredith GE et al (2013) Different roles of BDNF in nucleus accumbens core versus shell during the incubation of cue-induced cocaine craving and its long-term maintenance. J Neurosci 33(3):1130–1142

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Lu L, Dempsey J, Liu SY, Bossert JM, Shaham Y (2004) A single infusion of brain-derived neurotrophic factor into the ventral tegmental area induces long-lasting potentiation of cocaine seeking after withdrawal. J Neurosci 24(7):1604–1611

    Article  PubMed  CAS  Google Scholar 

  • Magalhães PV, Jansen K, Pinheiro RT, Colpo GD, da Motta LL, Klamt F et al (2012) Peripheral oxidative damage in early-stage mood disorders: a nested population-based case-control study. Int J Neuropsychopharmacol 15(8):1043–1050

    Article  PubMed  Google Scholar 

  • McGinty JF, Mendelson JE (2011) Is brain-derived neurotrophic factor a selective biomarker that predicts cocaine relapse outcomes? Biol Psychiatry 70(8):700–701

    Article  PubMed  Google Scholar 

  • McGinty JF, Whitfield TW Jr, Berglind WJ (2010) Brain-derived neurotrophic factor and cocaine addiction. Brain Res 1314:183–193

    Article  PubMed  CAS  Google Scholar 

  • Muriach M, López-Pedrajas R, Barcia JM, Sanchez-Villarejo MV, Almansa I, Romero FJ (2010) Cocaine causes memory and learning impairments in rats: involvement of nuclear factor kappa B and oxidative stress, and prevention by topiramate. J Neurochem 114(3):675–684

    Article  PubMed  CAS  Google Scholar 

  • Narvaez JC, Magalhães PV, Fries GR, Colpo GD, Czepielewski LS, Vianna P et al (2013) Peripheral toxicity in crack cocaine use disorders. Neurosci Lett 544:80–84

    Article  PubMed  CAS  Google Scholar 

  • NASCIMENTO ED (ed) (2002) WISC-III e WAIS-III: alterações nas versões originais americanas decorrentes das adaptações para uso no Brasil, FIGUEIREDO VLMd (ed) Vol. 15. Psicol. Reflex. Crit, Porto Alegre

    Google Scholar 

  • Nestler EJ (2004) Molecular mechanisms of drug addiction. Neuropharmacology 47(Suppl 1):24–32

    Article  PubMed  CAS  Google Scholar 

  • Ng F, Berk M, Dean O, Bush AI (2008) Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol 11(6):851–876

    PubMed  CAS  Google Scholar 

  • Numa R, Kohen R, Poltyrev T, Yaka R (2008) Tempol diminishes cocaine-induced oxidative damage and attenuates the development and expression of behavioral sensitization. Neuroscience 155(3):649–658

    Article  PubMed  CAS  Google Scholar 

  • Paim Kessler FH, Barbosa Terra M, Faller S, Ravy Stolf A, Carolina Peuker A, Benzano D et al (2012) Crack users show high rates of antisocial personality disorder, engagement in illegal activities and other psychosocial problems. Am J Addict 21(4):370–380

    Article  PubMed  Google Scholar 

  • Pomierny-Chamiolo L, Moniczewski A, Wydra K, Suder A, Filip M (2012) Oxidative stress biomarkers in some rat brain structures and peripheral organs underwent cocaine. Neurotox Res 23(1):92–102

    Article  PubMed  PubMed Central  Google Scholar 

  • Sarandol A, Sarandol E, Eker SS, Erdinc S, Vatansever E, Kirli S (2007) Major depressive disorder is accompanied with oxidative stress: short-term antidepressant treatment does not alter oxidative-antioxidative systems. Hum Psychopharmacol 22(2):67–73

    Article  PubMed  CAS  Google Scholar 

  • St Laurent R, Helm SR, Glenn MJ (2013) Reduced cocaine-seeking behavior in heterozygous BDNF knockout rats. Neurosci Lett 544:94–99

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Usdan SL, Schumacher JE, Milby JB, Wallace D, McNamara C, Michael M (2001) Crack cocaine, alcohol, and other drug use patterns among homeless persons with other mental disorders. Am J Drug Alcohol Abuse 27(1):107–120

    Article  PubMed  CAS  Google Scholar 

  • Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39(1):44–84

    Article  PubMed  CAS  Google Scholar 

  • von Diemen L, De Boni R, Kessler F, Benzano D, Pechansky F (2010) Risk behaviors for HCV- and HIV-seroprevalence among female crack users in Porto Alegre, Brazil. Arch Womens Ment Health 13(3):185–191

    Article  Google Scholar 

  • von Diemen L, Kapczinski F, Sordi AO, de Magalhães Narvaez JC, Guimarães LS, Kessler FH et al (2013) Increase in brain-derived neurotrophic factor expression in early crack cocaine withdrawal. Int J Neuropsychopharmacol 1–8

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Acknowledgments

Thanks go to Dr. Claudia Maciel Szobot, Dr. Ricardo Halpern, and Dr. Anderson Ray Stolf for helping with the collection of data from the control group and to the Molecular Psychiatry Laboratory (HCPA) staff for helping with the laboratorial analysis. This study was funded by Secretaria Nacional de Políticas sobre Drogas (National Secretariat for Alcohol and Drug Policies) of the Brazilian Ministry of Justice.

Conflict of interest

There is no conflict of interest.

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Authors and Affiliations

  1. Center for Drug and Alcohol Research, Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Rua Prof. Alvaro Alvim, 400, Porto Alegre, RS, CEP 90420-020, Brazil

    Anne Orgle Sordi, Felix Henrique Paim Kessler, Joana Correa de Magalhães Narvaez, Felipe Ornell & Lisia von Diemen

  2. Director of the Center for Drug and Alcohol Research, HCPA, UFRGS, Porto Alegre, RS, Brazil

    Flavio Pechansky

  3. Department of Legal Medicine and Psychiatry, UFRGS, Porto Alegre, RS, Brazil

    Flavio Pechansky & Flávio Kapczinski

  4. National Institute of Science and Technology for Translational Medicine, HCPA, UFRGS, Porto Alegre, RS, Brazil

    Flávio Kapczinski

  5. Bipolar Disorder Program and Molecular Psychiatry Laboratory, HCPA, Porto Alegre, RS, Brazil

    Flávio Kapczinski, Bianca Pfaffenseller, Carolina Gubert, Bianca Wollenhaupt de Aguiar & Joana Correa de Magalhães Narvaez

  6. Graduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, UFRGS, Porto Alegre, RS, Brazil

    Bianca Pfaffenseller, Carolina Gubert & Bianca Wollenhaupt de Aguiar

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  1. Anne Orgle Sordi
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  2. Flavio Pechansky
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  3. Felix Henrique Paim Kessler
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  6. Carolina Gubert
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  7. Bianca Wollenhaupt de Aguiar
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  8. Joana Correa de Magalhães Narvaez
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  9. Felipe Ornell
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  10. Lisia von Diemen
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Correspondence to Anne Orgle Sordi.

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Sordi, A.O., Pechansky, F., Kessler, F.H.P. et al. Oxidative stress and BDNF as possible markers for the severity of crack cocaine use in early withdrawal. Psychopharmacology 231, 4031–4039 (2014). https://doi.org/10.1007/s00213-014-3542-1

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  • DOI: https://doi.org/10.1007/s00213-014-3542-1

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