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Increased cocaine and amphetamine-regulated transcript cord blood levels in the newborns exposed to crack cocaine in utero

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Abstract

Background

Cocaine and amphetamine-regulated transcript (CART) is an endogenous antioxidant present since the embryonic period. CART is activated by high levels of dopamine and might be of interested in understanding the changes in the REDOX system associated with crack/cocaine intake. The goal of this study was to determine whether exposure to crack in utero is associated with increased CART levels.

Methods

In this cross-sectional study with consecutive sampling, we compared the umbilical cord blood (UCB) CART levels (μg/mL) of newborns exposed to crack/cocaine in utero (EN, n = 57) to levels in non-exposed newborns (NEN, n = 99). In addition, we compared serum CART levels between EN and NEN mothers, in the immediate postpartum period. Potential confounders, such as perinatal data (e.g., weight, Apgar, etc.), psychopathology (DSM-IV), and use of drugs other than crack (ASSIST) were assessed.

Results

According to general linear model analysis, the adjusted mean CART was significantly higher in EN (0.180, 95% CI 0.088–0.272) than in NEN (0.048, 95% CI 0.020–0.076; p < 0.002; d = 0.68). The difference in CART levels between EN and NEN mothers was not significant (p ≥ 0.05).

Conclusion

The increase in CART levels in EN UBC suggests a response to crack/cocaine-induced oxidative stress during gestational period, as a potential attempt of neuroprotection. In adult women in puerperium, however, this endogenous antioxidant recruitment does not seem to operate.

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References

  • Amorim P (2000) Mini International Neuropsychiatric Interview (MINI): validação de entrevistabreve para diagnóstico de transtornos mentais. Rev Bras Psiquiatr 22:106–115

    Article  Google Scholar 

  • Betancourt LM, Yang W, Brodsky NL et al (2011) Adolescents with and without gestational cocaine exposure: longitudinal analysis of inhibitory control, memory and receptive language. Neurotoxicol Teratol 33(1):36–46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Center for Behavioral Health Statistic and Quality (2015) Behavioral health trends in the United States: results from the 2014 national survey on drug use and health. rockville, maryland. (HHS Publication No. SMA 15–4927, NSDUH Series H-50). Available from: URL:http://www.samhsa.gov/data/sites/default/files/NSDUH-FRR1-2014/NSDUH-FRR1-2014.pdf

  • Cosmi EV, Maranghi L, Cosmi E, Gojnic M, Salernitano D (2002) Drugs and pregnancy. Ann Ist Super Sanita 38(3):265–270

    PubMed  Google Scholar 

  • Couceyro PR, Evans C, McKinzie A et al (2005) Cocaine- and amphetamine-regulated transcript (CART) peptides modulate the locomotor and motivational properties of psychostimulants. J Pharmacol Exp Ther 315(3):1091–1100

    Article  CAS  PubMed  Google Scholar 

  • Cunha GB, Rotta NT, Silva AR et al (2001) Prevalence of prenatal exposure to cocaine in a sample of newborns from a university teaching hospital. J Pediatr 77(5):369–373

    CAS  Google Scholar 

  • De Giovanni N, Marchetti D (2012) Cocaine and its metabolites in the placenta: a systematic review of the literature. Reprod Toxicol 33:1–14

    Article  PubMed  Google Scholar 

  • Dolkart LA, Plessinger MA, Woods JRJ (1990) Effect of alpha 1 receptor blockade upon maternal and fetal cardiovascular responses to cocaine. Obstet Gynecol 75(5):745–751

    CAS  PubMed  Google Scholar 

  • Friguls B, Joya X, Garcia-Serra J et al (2012) Assessment of exposure to drugs of abuse during pregnancy by hair analysis in a Mediterranean island. Addiction 107(8):1471–1479

    Article  PubMed  Google Scholar 

  • Hargrave B, Castle MC (1995) Intrauterine exposure to cocaine increased plasma ANP (atrial natriuretic peptide) but did not alter hypoxanthine concentrations in the sheep fetus. Life Sci 56(20):1689–1697

    Article  CAS  PubMed  Google Scholar 

  • Heal DJ, Gosden J, Smith SL (2014) Dopamine reuptake transporter (DAT) “inverse agonism”-a novel hypothesis to explain the enigmaticpharmacology of cocaine. Neuropharmacology 87:19–40

    Article  CAS  PubMed  Google Scholar 

  • Hehir MP, Laursen H, Higgins MF, Brennan DJ, O'Connor DP, McAuliffe FM (2012) Maternal and fetal cocaine- and amphetamine-regulated transcript in diabetic and non-diabetic pregnancy. Gynecol Endocrinol 28(9):682–685

    Article  CAS  PubMed  Google Scholar 

  • Henrique IFS, de Micheli D, de Lacerda RB, de Lacerda LA (2004) Formigoni MLOS [validation of the Brazilian version of alcohol, smoking and substance involvement screening test (ASSIST)]. Rev Assoc Med Bras 50(2):199–196

    Article  PubMed  Google Scholar 

  • Hubert GW, Jones DC, Moffett MC, Rogge G, Kuhar MJ (2008) CART Peptides as modulators of dopamine and psychostimulants and interactions with the mesolimbic dopaminergic system. Biochem Pharmacol 75(1):57–62

    Article  CAS  PubMed  Google Scholar 

  • Kastin AJ, Akerstrom V (1999) Entry of CART into brain is rapid but not inhibited by excess CART or leptin. Am J Physiol 277(5):E901–E904

    CAS  PubMed  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  CAS  PubMed  Google Scholar 

  • Lester BM, Tronick EZ, LaGasse L et al (2002) The maternal lifestyle study: effects of substance exposure during pregnancy on neurodevelopmental outcome in 1-month-old infants. Pediatrics 110(6):1182–1192

    Article  PubMed  Google Scholar 

  • Lipton JW, Vu TQ, Ling Z, Gyawali S, Mayer JR, Carvey PM (2002) Prenatal cocaine exposure induces an attenuation of uterine blood flow in the rat. Neurotoxicol Teratol 24(2):143–148

    Article  CAS  PubMed  Google Scholar 

  • Lipton JW, Gyawali S, Borys ED, Koprich JB, Ptaszny M, McGuire SO (2003) Prenatal cocaine administration increases glutathione and alpha-tocopherol oxidation in fetal rat brain. Brain Res Dev Brain Res 147(1–2):77–84

    Article  CAS  PubMed  Google Scholar 

  • Mao P (2011) Potential antidepressant role of neurotransmitter CART: implications for mental disorders. Depress Res Treat 762139

  • Mao P, Meshul CK, Thuillier P, Goldberg NR, Reddy PH (2012) CART Peptide is a potential endogenous antioxidant and preferentially localized in mitochondria. PLos One 7(1):e29343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mardini V, Rohde LA, Ceresér KMM, Gubert CM, da Silva EG, Xavier F et al (2017) TBARS and BDNF levels in newborns exposed to crack/cocaine during pregnancy: a comparative study. Rev Bras Psiquiatr 39(3):263–266

    Article  PubMed  Google Scholar 

  • Mattar FN (1995) Análise critica dos estudos de estratificação sócio-econômicada ABAAbipeme. Rev Adm:57–74

  • Min MO, Minnes S, Lang A et al (2014) Externalizing behavior and substance use related problems at 15 years in prenatally cocaine exposed adolescents. J Adolesc 37(3):269–279

    Article  PubMed  PubMed Central  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  CAS  PubMed  Google Scholar 

  • do Nascimento E, de Figueiredo VLM (2002) WISC-III e WAIS-III: alterações nas versões originais americanas decorrentes das adaptações para uso no Brasil. Psico Reflexão e Crítica 15:603–612

    Article  Google Scholar 

  • Netcord & FACT (2012) International standards for cord blood collection, Banking, And Release For Administration

  • Parolin M, Simonelli A, Mapelli D, Sacco M, Cristofalo P (2016) Parental substance abuse as an early traumatic event. Preliminary findings on neuropsychological and personality functioning in young drug addicts exposed to drugs early. Front Psychol 7:887

    Article  PubMed  PubMed Central  Google Scholar 

  • Patel TG, Laungani RG, Grose EA, Dow-Edwards DL (1999) Cocaine decreases uteroplacental blood flow in the rat. Neurotoxicol Teratol 21(5):559–565

    Article  CAS  PubMed  Google Scholar 

  • Qiu B, Hu S, Liu L, Chen M, Wang L, Zeng X, Zhu S (2013) CART Attenuates endoplasmic reticulum stress response induced by cerebral ischemia and reperfusion through upregulating BDNF synthesis and secretion. Biochem Biophys Res Commun 436(4):655–659

    Article  CAS  PubMed  Google Scholar 

  • Rogge G, Jones D, Hubert GW, Lin Y, Kuhar MJ (2008) CART Peptides: regulators of body weight, reward and other functions. Nat Rev Neurosci 9(10):747–758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sathanoori R, Olde B, Erlinge D, Göransson O, Wierup N (2013) Cocaine- and amphetamine-regulated transcript (CART) protects beta cells against glucotoxicity and increases cell proliferation. J BiolChem 288(5):3208–3218

    CAS  Google Scholar 

  • Silva N Jr, Szobot CM, Shih MC et al (2014) Searching for a neurobiological basis for self-medication theory in ADHD comorbid with substance use disorders: an in vivo study of dopamine transporters using (99m)Tc-TRODAT-1 SPECT. Clin Nucl Med 39(2):e129–e134

    PubMed  Google Scholar 

  • Uys JD, Knackstedt L, Hurt P et al (2011) Cocaine induced adaptations in cellular redox balance contributes to enduring behavioral plasticity. Neuropsychopharmacology 36:2551–2560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Uys JD, Mulholland PJ, Townsend DM (2014) Glutathione and redox signaling in substance abuse. Biomed Pharmacother 68(6):799–807

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wechsler D (2004) WAIS-III: Escala de Inteligência Wechsler para Adultos. (Casa do Psicologo)

  • Woods JR (1992) Cardiovascular effects of cocaine in pregnancy and on the fetus. NIDA Res Monogr 119:111–115

    CAS  PubMed  Google Scholar 

  • Zaparte A, Viola TW, Grassi-Oliveira R et al (2015) Early abstinence of crack-cocaine is effective to attenuate oxidative stress and to improve antioxidant defences. Psychopharmacology 232(8):1405–1413

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We acknowledge all participants who took part in the present study and CAPES-PNPD (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Programa Nacional de Pós-Doutorado), edital 10/2009, and FIPE-HCPA (Fundo de Incentivo à Pesquisa-Hospital de Clínicas de Porto Alegre) for providing funding to this research.

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Authors and Affiliations

  1. Graduate Program in Psychiatry and Behavioral Sciences, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2400, Santa Cecília, Porto Alegre, RS, 90035-003, Brazil

    Rodrigo Ritter Parcianello, Keila Maria Mendes Ceresér, Luis Augusto Paim Rhode, Flávio Pechansky & Claudia Maciel Szobot

  2. Child and Adolescent Psychiatry Service (SPIA), Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, 4° andar, sala 400N, Santa Cecília, Porto Alegre, RS, 90035-903, Brazil

    Victor Mardini, Maria Lucrécia Scherer Zavaschi, Luis Augusto Paim Rhode & Claudia Maciel Szobot

  3. Laboratory of Molecular Psychiatry and Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), HCPA, UFRGS, Rua Ramiro Barcelos, 2350, Santa Cecília, Porto Alegre, RS, 90035-903, Brazil

    Keila Maria Mendes Ceresér & Carolina Gubert

  4. Department of Psychiatry, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA

    Daniel D. Langleben

  5. Program in Biomedical Sciences, Centro Universitário Metodista–IPA, Rua Dona Leonor, 340, Rio Branco, Porto Alegre, RS, 90420-004, Brazil

    Fernando Xavier

  6. Instituto Nacional de Psiquiatria do Desenvolvimento (INPD), Rua Dr. Ovídio Pires de Campos, 785, 1° andar, sala 6, Ala Sul, Cerqueira Cesar, São Paulo, SP, 05403-010, Brazil

    Luis Augusto Paim Rhode

  7. Department of Psychiatry, UFRGS, Rua Ramiro Barcelos, 2400, Santa Cecília, Porto Alegre, RS, 90035-003, Brazil

    Luis Augusto Paim Rhode & Flávio Pechansky

  8. Center for Drug and Alcohol Research, HCPA, UFRGS, Rua Professor Álvaro Alvim, 400, Rio Branco, Porto Alegre, RS, 90420-020, Brazil

    Flávio Pechansky & Claudia Maciel Szobot

  9. Graduate Program in Biological Sicences, Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Ramiro Barcelos, 2600, Santa Cecília, Porto Alegre, RS, 90035-003, Brazil

    Carolina Gubert

Authors
  1. Rodrigo Ritter Parcianello
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  2. Victor Mardini
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  3. Keila Maria Mendes Ceresér
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  4. Daniel D. Langleben
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  5. Fernando Xavier
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  6. Maria Lucrécia Scherer Zavaschi
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  7. Luis Augusto Paim Rhode
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  8. Flávio Pechansky
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  9. Carolina Gubert
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  10. Claudia Maciel Szobot
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Corresponding author

Correspondence to Claudia Maciel Szobot.

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Conflicts of interest

Luis Augusto Rohde has been on the speakers’ bureau and/or acted as a consultant for Eli Lilly, Janssen-Cilag, Novartis, and Shire and receives royalties from Oxford Press and Artmed. The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by Luis Augusto Rohde have received unrestricted educational and research support from the following pharmaceutical companies: Eli Lilly, Janssen-Cilag, Novartis, and Shire. Claudia M. Szobot has been on the speakers’ bureau of Novartis. Dr. Langleben served as a consultant for Alkermes Inc. No relevant conflicts to disclose. The other authors have no conflicts of interest to declare.

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Parcianello, R.R., Mardini, V., Ceresér, K.M.M. et al. Increased cocaine and amphetamine-regulated transcript cord blood levels in the newborns exposed to crack cocaine in utero. Psychopharmacology 235, 215–222 (2018). https://doi.org/10.1007/s00213-017-4759-6

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  • DOI: https://doi.org/10.1007/s00213-017-4759-6

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