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Long-term parental methamphetamine exposure of mice influences behavior and hippocampal DNA methylation of the offspring

Molecular Psychiatry volume 20, pages 232–239 (2015)Cite this article

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Abstract

The high rate of methamphetamine (METH) abuse among young adults and women of childbearing age makes it imperative to determine the long-term effects of METH exposure on the offspring. We hypothesized that parental METH exposure modulates offspring behavior by disrupting epigenetic programming of gene expression in the brain. To simulate the human pattern of drug use, male and female C57Bl/6J mice were exposed to escalating doses of METH or saline from adolescence through adulthood; following mating, females continue to receive drug or saline through gestational day 17. F1 METH male offspring showed enhanced response to cocaine-conditioned reward and hyperlocomotion. Both F1 METH male and female offspring had reduced response to conditioned fear. Cross-fostering experiments have shown that certain behavioral phenotypes were modulated by maternal care of either METH or saline dams. Analysis of offspring hippocampal DNA methylation showed differentially methylated regions as a result of both METH in utero exposure and maternal care. Our results suggest that behavioral phenotypes and epigenotypes of offspring that were exposed to METH in utero are vulnerable to (a) METH exposure during embryonic development, a period when wide epigenetic reprogramming occurs, and (b) postnatal maternal care.

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References

  1. Kuczenski R . Effects of phospholipases on the kinetic properties of rat striatal membrane-bound tyrosine hydroxylase. J Neurochem 1983; 40: 821–829.

    Article  CAS  PubMed  Google Scholar 

  2. Sulzer D, Chen TK, Lau YY, Kristensen H, Rayport S, Ewing A . Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport. J Neurosci 1995; 15: 4102–4108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Darke S, Kaye S, McKetin R, Duflou J . Major physical and psychological harms of methamphetamine use. Drug Alcohol Rev 2008; 27: 253–262.

    Article  PubMed  Google Scholar 

  4. Homer BD, Solomon TM, Moeller RW, Mascia A, DeRaleau L, Halkitis PN . Methamphetamine abuse and impairment of social functioning: a review of the underlying neurophysiological causes and behavioral implications. Psychol Bull 2008; 134: 301–310.

    Article  PubMed  Google Scholar 

  5. Pennay AE, Lee NK . Putting the call out for more research: the poor evidence base for treating methamphetamine withdrawal. Drug Alcohol Rev 2011; 30: 216–222.

    Article  PubMed  Google Scholar 

  6. Marshall BD, Werb D . Health outcomes associated with methamphetamine use among young people: a systematic review. Addiction 2010; 105: 991–1002.

    Article  PubMed  Google Scholar 

  7. Ellison G . Stimulant-induced psychosis, the dopamine theory of schizophrenia, and the habenula. Brain Res Brain Res Rev 1994; 19: 223–239.

    Article  CAS  PubMed  Google Scholar 

  8. Grant KM, LeVan TD, Wells SM, Li M, Stoltenberg SF, Gendelman HE et al. Methamphetamine-associated psychosis. J Neuroimmune Pharmacol 2012; 7: 113–139.

    Article  PubMed  Google Scholar 

  9. Grelotti DJ, Kanayama G, Pope HG Jr . Remission of persistent methamphetamine-induced psychosis after electroconvulsive therapy: presentation of a case and review of the literature. Am J Psychiatry 2010; 167: 17–23.

    Article  PubMed  Google Scholar 

  10. Volkow ND, Chang L, Wang GJ, Fowler JS, Leonido-Yee M, Franceschi D et al. Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. Am J Psychiatry 2001; 158: 377–382.

    Article  CAS  PubMed  Google Scholar 

  11. Substance Abuse and Mental Health Services Administration (SAMHSA), Office of Applied Studies. Results from the 2007 National Survey on Drug Use and Health: National Findings (NSDUH Series H-34, DHHS Publication No. SMA 08-4343). Rockville, MD, USA, 2008.

  12. American College of Obstetricians and Gynecologists Committee on Health Care for Underserved Women. Committee Opinion No. 479: Methamphetamine abuse in women of reproductive age. Obstet Gynecol 2011; 117: 751–755.

    Article  Google Scholar 

  13. Lester BM, LaGasse LL . Children of addicted women. J Addict Dis 2010; 29: 259–276.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Chomchai C, Na Manorom N, Watanarungsan P, Yossuck P, Chomchai S . Methamphetamine abuse during pregnancy and its health impact on neonates born at Siriraj Hospital, Bangkok, Thailand. Southeast Asian J Trop Med Public Health 2004; 35: 228–231.

    PubMed  Google Scholar 

  15. Dixon SD, Bejar R . Echoencephalographic findings in neonates associated with maternal cocaine and methamphetamine use: incidence and clinical correlates. J Pediatr 1989; 115: 770–778.

    Article  CAS  PubMed  Google Scholar 

  16. Little BB, Snell LM, Gilstrap LC 3rd . Methamphetamine abuse during pregnancy: outcome and fetal effects. Obstet Gynecol 1988; 72: 541–544.

    CAS  PubMed  Google Scholar 

  17. Smith LM, LaGasse LL, Derauf C, Grant P, Shah R, Arria A et al. Prenatal methamphetamine use and neonatal neurobehavioral outcome. Neurotoxicol Teratol 2008; 30: 20–28.

    Article  CAS  PubMed  Google Scholar 

  18. Eriksson M, Jonsson B, Steneroth G, Zetterström R . Cross-sectional growth of children whose mothers abused amphetamines during pregnancy. Acta Paediatr 1994; 83: 612–617.

    Article  CAS  PubMed  Google Scholar 

  19. Chang L, Alicata D, Ernst T, Volkow N . Structural and metabolic brain changes in the striatum associated with methamphetamine abuse. Addiction 2007; 102: 16–32.

    Article  PubMed  Google Scholar 

  20. Chang L, Smith LM, LoPresti C, Yonekura ML, Kuo J, Walot I et al. Smaller subcortical volumes and cognitive deficits in children with prenatal methamphetamine exposure. Psychiatry Res 2004; 132: 95–106.

    Article  CAS  PubMed  Google Scholar 

  21. Cloak CC, Ernst T, Fujii L, Hedemark B, Chang L . Lower diffusion in white matter of children with prenatal methamphetamine exposure. Neurology 2009; 72: 2068–2075.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Smith L, Yonekura ML, Wallace T, Berman N, Kuo J, Berkowitz C . Effects of prenatal methamphetamine exposure on fetal growth and drug withdrawal symptoms in infants born at term. J Dev Behav Pediatr 2003; 24: 17–23.

    Article  PubMed  Google Scholar 

  23. Struthers JM, Hansen RL . Visual recognition memory in drug-exposed infants. J Dev Behav Pediatr 1992; 13: 108–111.

    Article  CAS  PubMed  Google Scholar 

  24. Chang L, Cloak C, Jiang CS, Farnham S, Tokeshi B, Buchthal S et al. Altered neurometabolites and motor integration in children exposed to methamphetamine in utero. Neuroimage 2009; 48: 391–397.

    Article  CAS  PubMed  Google Scholar 

  25. Derauf C, LaGasse LL, Smith LM, Grant P, Shah R, Arria A et al. Demographic and psychosocial characteristics of mothers using meth-amphetamine during pregnancy: preliminary results of the infant development, environment, and lifestyle study (IDEAL). Am J Drug Alcohol Abuse 2007; 33: 281–289.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Shah R, Diaz SD, Arria A, LaGasse LL, Derauf C, Newman E et al. Prenatal methamphetamine exposure and short-term maternal and infant medical outcomes. Am J Perinatol 2012; 29: 391–400.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Good MM, Solt I, Acuna JG, Rotmensch S, Kim MJ . Methamphetamine use during pregnancy: maternal and neonatal implications. Obstet Gynecol 2010; 116: 330–334.

    Article  PubMed  Google Scholar 

  28. Bubenikova-Valesova V, Kacer P, Syslova K, Rambousek L, Janovsky M, Schutova B et al. Prenatal methamphetamine exposure affects the mesolimbic dopaminergic system and behavior in adult offspring. Int J Dev Neurosci 2009; 27: 525–530.

    Article  CAS  PubMed  Google Scholar 

  29. Šlamberová R, Yamamotová A, Schutová B, Hrubá L, Pometlová M . Impact of prenatal methampheta-mine exposure on the sensitivity to the same drug in adult male rats. Prague Med Rep 2011; 112: 102–114.

    PubMed  Google Scholar 

  30. Jeng W, Wong AW, Ting-A-Kee R, Wells PG . Methamphetamine-enhanced embryonic oxidative DNA damage and neurodevelopmental deficits. Free Radic Biol Med 2005; 39: 317–326.

    Article  CAS  PubMed  Google Scholar 

  31. Quinn R . Comparing rat’s to human’s age: How old is my rat in people years? Nutrition 2005; 21: 775–777.

    Article  PubMed  Google Scholar 

  32. Gentry WB, Ghafoor AU, Wessinger WD, Laurenzana EM, Hendrickson HP, Owens SM . (+)-Methamphetamine-induced spontaneous behavior in rats depends on route of (+)METH administration. Pharmacol Biochem Behav 2004; 79: 751–760.

    Article  CAS  PubMed  Google Scholar 

  33. Meaney MJ . Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci 2001; 24: 1161–1192.

    Article  CAS  PubMed  Google Scholar 

  34. Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR et al. Epigenetic programming by maternal behavior. Nat Neurosci 2004; 7: 847–854.

    Article  CAS  PubMed  Google Scholar 

  35. Hickman DL, Swan MP . Effects of age of pups and removal of existing litter on pup survival during cross-fostering between multiparous outbred mice. J Am Assoc Lab Anim Sci 2011; 50: 641–646.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Itzhak Y, Gandia C, Huang PL, Ali SF . Resistance of neuronal nitric oxide synthase-deficient mice to methamphetamine-induced dopaminergic neurotoxicity. J Pharmacol Exp Ther 1998; 284: 1040–1047.

    CAS  PubMed  Google Scholar 

  37. Itzhak Y, Martin JL . Cocaine-induced conditioned place preference in mice: Induction, extinction and reinstatement by related psychostimulants. Neuropsychopharmacology 2002; 26: 130–134.

    Article  CAS  PubMed  Google Scholar 

  38. Vassoler FM, White SL, Schmidt HD, Sadri-Vakili G, Pierce RC . Epigenetic inheritance of a cocaine-resistance phenotype. Nat Neurosci 2013; 16: 42–47.

    Article  CAS  PubMed  Google Scholar 

  39. Itzhak Y, Liddie S, Anderson KL . Sodium butyrate-induced histone acetylation strengthens the expression of cocaine-associated contextual memory. Neurobiol Learn Mem 2013; 102: 34–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kelley JB, Balda MA, Anderson KL, Itzhak Y . Impairments in fear conditioning in mice lacking the nNOS gene. Learn Mem 2009; 16: 371–378.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Bourin M, Hascoët M . The mouse light/dark box test. Eur J Pharmacol 2003; 463: 55–65.

    Article  CAS  PubMed  Google Scholar 

  42. Crawley J, Goodwin FK . Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines. Pharmacol Biochem Behav 1980; 13: 167–170.

    Article  CAS  PubMed  Google Scholar 

  43. Onaivi ES, Martin BR . Neuropharmacological and physiological validation of a computer-controlled two-compartment black and white box for the assessment of anxiety. Prog Neuropsychopharmacol Biol Psychiatry 1989; 13: 963–976.

    Article  CAS  PubMed  Google Scholar 

  44. Tusnády GE, Simon I, Váradi A, Arányi T . BiSearch: primer-design and search tool for PCR on bisulfite-treated genomes. Nucleic Acids Res 2005; 33: e9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Frantz KJ, O'Dell LE, Parsons LH . Behavioral and Neurochemical Responses to Cocaine in Periadolescent and Adult Rats. Neuropsychopharmacology 2007; 32: 625–637.

    Article  CAS  PubMed  Google Scholar 

  46. Cho AK, Melega WP, Kuczenski R, Segal DS . Relevance of pharmacokinetic parameters in animal models of methamphetamine abuse. Synapse 2011; 39: 161–166.

    Article  Google Scholar 

  47. Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, Meirelles GV et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics 2013; 14: 128–134.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Voigt P, Tee WW, Reinberg D . A double take on bivalent promoters. Genes Dev 2013; 27: 1318–1338.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. United National Office on Drugs and Crime. World Drug Report, Analysis Vol. 1. United Nations Publication: Vienna, Austria, 2004.

  50. Substance Abuse and Mental Health Services Administration. Treatment Episode Data Set (TEDS). 1999–2009. National Admissions to Substance Abuse Treatment Services, DASIS Series, S-56, HHS Publication No. (SMA) 11-4646, 2011.

  51. LaGasse LL, Derauf C, Smith LM, Newman E, Shah R, Neal C et al. Prenatal methamphetamine exposure and childhood behavior problems at 3 and 5 years of age. Pediatrics 2012; 229: 681–688.

    Article  Google Scholar 

  52. LaGasse LL, Wouldes T, Newman E, Smith LM, Shah RZ, Derauf C et al. Prenatal methamphetamine exposure and neonatal neurobehavioral outcome in the USA and New Zealand. Neurotoxicol Teratol 2011; 33: 166–175.

    Article  CAS  PubMed  Google Scholar 

  53. Johnson BA, Roache JD, Ait-Daoud N, Wells LT, Wallace CL, Dawes MA et al. Effects of acute topiramate dosing on methamphetamine-induced subjective mood. Int J Neuropsychopharmacol 2007; 10: 85–98.

    Article  CAS  PubMed  Google Scholar 

  54. Ghahremani DG, Tabibnia G, Monterosso J, Hellemann G, Poldrack RA, London ED . Effect of modafinil on learning and task-related brain activity in methamphetamine-dependent and healthy individuals. Neuropsychopharmacology 2011; 36: 950–959.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Alicata D, Chang L, Cloak C, Abe K, Ernst T . Higher diffusion in striatum and lower fractional anisotrophy in white matter of methamphetamine users. Psychiatry Res 2009; 174: 1–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Achat-Mendes C, Ali SF, Itzhak Y . Differential effects of amphetamines-induced neurotoxicity on appetitive and aversive Pavlovian conditioning in mice. Neuropsychopharmacology 2005; 30: 1128–1137.

    Article  CAS  PubMed  Google Scholar 

  57. Stephans S, Yamamoto B . Methamphetamines pretreatment and the vulnerability of the striatum to methamphetamine neurotoxicity. Neuroscience 1996; 72: 593–600.

    Article  CAS  PubMed  Google Scholar 

  58. Van der Veen R, Abrous DN, De Kloet ER, Piazza PV, Koehl M . Impact of intra- and interstrain cross-fostering on mouse maternal care. Genes Brain Behav 2008; 7: 184–192.

    Article  CAS  PubMed  Google Scholar 

  59. Curley JP, Rock V, Moynihan AM, Bateson P, Keverne EB, Champagne FA . Developmental shifts in the behavioral phenotypes of inbred mice: the role of postnatal and juvenile social experiences. Behav Genet 2010; 40: 220–232.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. LaPlant Q, Vialou V, Covington HE 3rd, Dumitriu D, Feng J, Warren BL et al. Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens. Nat Neurosci 2010; 13: 1137–1143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Torregrossa MM, Taylor JR . Learning to forget: manipulating extinction and reconsolidation processes to treat addiction. Psychopharmacology 2013; 226: 659–672.

    Article  CAS  PubMed  Google Scholar 

  62. Fanselow MS, Dong HW . Are the dorsal and ventral hippocampus functionally distinct structures? Neuron 2010; 65: 7–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Swatt JD . Hippocampal function in cognition. Psychopharmacology 2004; 174: 99–110.

    Google Scholar 

  64. Meyers RA, Zavala AR, Neisewander JL . Dorsal, but not ventral, hippocampal lesions disrupt cocaine place conditioning. Neuroreport 2003; 14: 2127–2131.

    Article  PubMed  Google Scholar 

  65. Meyers RA, Zavala AR, Speer CM, Neisewander JL . Dorsal hippocampus inhibition disrupts acquisition and expression, but not consolidation, of cocaine conditioned place preference. Behav Neurosci 2006; 120: 401–412.

    Article  CAS  PubMed  Google Scholar 

  66. Shohamy D, Adcock RA . Dopamine and adaptive memory. Trends Cogn Sci 2010; 14: 464–472.

    Article  CAS  PubMed  Google Scholar 

  67. Britt JP, Benaliouad F, McDevitt RA, Stuber GD, Wise RA, Bonci A . Synaptic and behavioral profile of multiple glutamatergic inputs to the nucleus accumbens. Neuron 2012; 76: 790–803.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Dong HW, Swanson LW, Chen L, Fanselow MS, Toga AW . Genomic-anatomic evidence for distinct functional domains in hippocampal field CA1. Proc Natl Acad Sci USA 2009; 106: 11794–1179.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Yin H, Bardgett ME, Csernansky JG . Kainic acid lesions disrupt fear-mediated memory processing. Neurobiol Learn Mem 2002; 77: 389–401.

    Article  PubMed  Google Scholar 

  70. Bardgett ME, Boeckman R, Krochmal D, Fernando H, Ahrens R, Csernansky JG . NMDA receptor blockade and hippocampal neuronal loss impair fear conditioning and position habit reversal in C57Bl/6 mice. Brain Res Bull 2003; 60: 131–142.

    Article  CAS  PubMed  Google Scholar 

  71. Martin MV, Dong H, Bertchume A, Csernansky JG . Low dose quetiapine reverses deficits in contextual and cued fear conditioning in rats with excitotoxin-induced hippocampal neuropathy. Pharmacol Biochem Behav 2005; 82: 263–269.

    Article  CAS  PubMed  Google Scholar 

  72. Hunsaker MR, Kesner RP . Dissociations across the dorsal-ventral axis of CA3 and CA1 for encoding and retrieval of contextual and auditory-cued fear. Neurobiol Learn Mem 2008; 89: 61–69.

    Article  PubMed  Google Scholar 

  73. Day JJ, Sweatt JD . DNA methylation and memory formation. Nat Neurosci 2010; 13: 1319–1323.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Suderman M, McGowan PO, Sasaki A, Huang TC, Hallett MT, Meaney MJ et al. Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus. Proc Natl Acad Sci USA 2012; 109: 17266–17272.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Novikova SI, He F, Bai J, Cutrufello NJ, Lidow MS, Undieh AS . Maternal cocaine administration in mice alters DNA methylation and gene expression in hippocampal neurons of neonatal and prepubertal offspring. PLoS ONE 2008; 3: e1919.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Justinova Z, Ferre S, Segal PN, Antoniou K, Solinas M, Pappas LA et al. Involvement of adenosine A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of cocaine and methamphetamine in rats. J Pharmacol Exp Ther 2003; 307: 977–986.

    Article  CAS  PubMed  Google Scholar 

  77. Chen Q, Zhu X, Zhang Y, Wetsel WC, Lee TH, Zhang X . Integrin-linked kinase is involved in cocaine sensitization by regulating PSD-95 and synapsin I expression and GluR1 Ser845 phosphorylation. J Mol Neurosci 2010; 40: 284–294.

    Article  CAS  PubMed  Google Scholar 

  78. Reissner KJ, Uys JD, Schwacke JH, Comte-Walters S, Rutherford-Bethard JL, Dunn TE et al. AKAP signaling in reinstated cocaine seeking revealed by iTRAQ proteomic analysis. J Neurosci 2011; 31: 5648–5658.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Krasnova IN, Chiflikyan M, Justinova Z, McCoy MT, Ladenheim B, Jayanthi S et al. CREB phosphorylation regulates striatal transcriptional responses in the self-administration model of methamphetamine addiction in the rat. Neurobiol Dis 2013; 58: 132–1343.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Renthal W, Maze I, Krishnan V, Covington HE 3rd, Xiao G, Kumar A et al. Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli. Neuron 2007; 56: 517–529.

    Article  CAS  PubMed  Google Scholar 

  81. Niikura K, Zhou Y, Ho A, Kreek MJ . Proopiomelanocortin (POMC) expression and conditioned place aversion during protracted withdrawal from chronic intermittent escalating-dose heroin in POMC-EGFP promoter transgenic mice. Neuroscience 2013; 236: 220–232.

    Article  CAS  PubMed  Google Scholar 

  82. Robison AJ, Vialou V, Mazei-Robison M, Feng J, Kourrich S, Collins M et al. Behavioral and structural responses to chronic cocaine require a feedforward loop involving ΔFosB and calcium/calmodulin-dependent protein kinase II in the nucleus accumbens shell. J Neurosci 2013; 33: 4295–4307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Miller JS, Tallarida RJ, Unterwald EM . Cocaine-induced hyperactivity and sensitization are dependent on GSK3. Neuropharmacology 2009; 56: 1116–1123.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Xu CM, Wang J, Wu P, Zhu WL, Li QQ, Xue YX et al. Glycogen synthase kinase 3beta in the nucleus accumbens core mediates cocaine-induced behavioral sensitization. J Neurochem 2009; 111: 1357–1368.

    Article  CAS  PubMed  Google Scholar 

  85. Mash DC, ffrench-Mullen J, Adi N, Qin Y, Buck A, Pablo J . Gene expression in human hippocampus from cocaine abusers identifies genes which regulate extracellular matrix remodeling. PLoS ONE 2007; 2: e1187.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Shonesy BC, Thiruchelvam K, Parameshwaran K, Rahman EA, Karuppagounder SS, Huggins KW et al. Central insulin resistance and synaptic dysfunction in intracerebroventricular-streptozotocin injected rodents. Neurobiol Aging 2012; 33: e5–18.

    Article  CAS  Google Scholar 

  87. Moita MA, Lamprecht R, Nader K, LeDoux JE . A-kinase anchoring proteins in amygdala are involved in auditory fear memory. Nat Neurosci 2002; 5: 837–838.

    Article  CAS  PubMed  Google Scholar 

  88. Govorko D, Bekdash RA, Zhang C, Sarkar DK . Male germline transmits fetal alcohol adverse effect on hypothalamic proopiomelanocortin gene across generations. Biol Psychiatry 2012; 72: 378–388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. West NA, Kechris K, Dabelea D . Exposure to maternal diabetes in utero and DNA methylation patterns in the offspring. Immunometabolism 2013; 1: 1–9.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Dowling AL, Iannacone EA, Zoeller RT . Maternal hypothyroidism selectively affects the expression of neuroendocrine-specific protein A messenger ribonucleic acid in the proliferative zone of the fetal rat brain cortex. Endocrinology 2001; 142: 390–399.

    Article  CAS  PubMed  Google Scholar 

  91. Bohuslavova R, Skvorova L, Sedmera D, Semenza GL, Pavlinkova G . Increased susceptibility of HIF-1α heterozygous-null mice to cardiovascular malformations associated with maternal diabetes. J Mol Cell Cardiol 2013; 60: 129–141.

    Article  CAS  PubMed  Google Scholar 

  92. Grisel JE, Bartels JL, Allen SA, Turgeon VL . Influence of beta-Endorphin on anxious behavior in mice: interaction with EtOH. Psychopharmacology 2008; 200: 105–115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Nguyen AT, Marquez P, Hamid A, Kieffer B, Friedman TC, Lutfy K . The rewarding action of acute cocaine is reduced in β-endorphin deficient but not in μ opioid receptor knockout mice. Eur J Pharmacol 2012; 686: 50–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported in part by grant RO1DA026878 and R21DA029404 from the National Institute on Drug Abuse, National Institutes of Health (to YI) and award from the University of Miami Specialized Center of Research on Addiction and Health in Women, Children and Adolescence (to YI & JIY). We are thankful for the excellent technical support of Karen L Anderson, Michael W Kaplan and Shervin Liddie.

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  1. Department of Psychiatry and Behavioral Sciences, Cellular and Molecular Pharmacology and Neuroscience Division, University of Miami Miller School of Medicine, Miami, FL, USA,

    Y Itzhak

  2. John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA,

    I Ergui & J I Young

  3. Dr John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA

    J I Young

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Itzhak, Y., Ergui, I. & Young, J. Long-term parental methamphetamine exposure of mice influences behavior and hippocampal DNA methylation of the offspring. Mol Psychiatry 20, 232–239 (2015). https://doi.org/10.1038/mp.2014.7

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