title: Buprenorphine, methadone, and morphine treatment during pregnancy: behavioral effects on the offspring in rats.
abstract: Methadone and buprenorphine are widely used for treating people with opioid dependence, including pregnant women. Prenatal exposure to opioids has devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. This study aimed at comparing the behavioral outcomes of young rats prenatally exposed to buprenorphine, methadone, and morphine. Pregnant Sprague-Dawley rats were administered saline, morphine, methadone, and buprenorphine during embryonic days 3-20. The cognitive function, social interaction, anxiety-like behaviors, and locomotor activity of offsprings were examined by novel object recognition test, social interaction test, light-dark transition test, elevated plus-maze, and open-field test between 6 weeks and 10 weeks of age. Prenatal exposure to methadone and buprenorphine did not affect locomotor activity, but significantly impaired novel object recognition and social interaction in both male and female offsprings in the same manner as morphine. Although prenatal exposure to methadone or buprenorphine increased anxiety-like behaviors in the light-dark transition in both male and female offsprings, the effects were less pronounced as compared to that of morphine. Methadone affected elevated plus-maze in both sex, but buprenorphine only affected the female offsprings. These findings suggest that buprenorphine and methadone maintenance therapy for pregnant women, like morphine, produced detrimental effects on cognitive function and social behaviors, whereas the offsprings of such women might have a lower risk of developing anxiety disorders.
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan ; Master and PhD Program in Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan.
authors.forename: Hwei-Hsien
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Center for Drug Abuse and Addiction, China Medical University Hospital, Taichung, Taiwan ; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chiang
authors.affiliation: Master Program in Physiological and Anatomical Medicine, School of Medicine, Tzu Chi University, Hualien, Taiwan ; Department of Physiology, School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Zung Fan
authors.initials: ZF
authors.lastname: Yuan
authors.affiliation: Master Program in Physiological and Anatomical Medicine, School of Medicine, Tzu Chi University, Hualien, Taiwan ; Department of Physiology, School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Chung-Chih
authors.initials: CC
authors.lastname: Kuo
authors.affiliation: Master and PhD Program in Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan.
authors.forename: Mei-Dan
authors.initials: MD
authors.lastname: Lai
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan.
authors.forename: Tsai-Wei
authors.initials: TW
authors.lastname: Hung
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan ; Center for Drug Abuse and Addiction, China Medical University Hospital, Taichung, Taiwan ; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Ing-Kang
authors.initials: IK
authors.lastname: Ho
authors.affiliation: Master and PhD Program in Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan ; Department of Psychiatry, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
authors.forename: Shao-Tsu
authors.initials: ST
authors.lastname: Chen
keywords: anxiety; buprenorphine; cognitive function; methadone; prenatal; social behavior
references.citation: Percept Mot Skills. 1980 Jun;50(3 Pt 2):1119-24
references.pmid: 7413386
references.citation: Mt Sinai J Med. 2000 Oct-Nov;67(5-6):347-64
references.pmid: 11064485
references.citation: Br J Pharmacol. 2006 Apr;147(8):864-72
references.pmid: 16491101
references.citation: Toxicol Lett. 2003 Apr 11;140-141:171-81
references.pmid: 12676464
references.citation: Neurobehav Toxicol Teratol. 1982 Jul-Aug;4(4):429-34
references.pmid: 7121694
references.citation: Genes Brain Behav. 2003 Apr;2(2):80-92
references.pmid: 12884965
references.citation: J Neurochem. 1978 Jul;31(1):49-54
references.pmid: 671039
references.citation: N Engl J Med. 2010 Dec 9;363(24):2320-31
references.pmid: 21142534
references.citation: Pediatrics. 1979 Jan;63(1):135-41
references.pmid: 86983
references.citation: J Pharmacol Exp Ther. 2001 Aug;298(2):797-804
references.pmid: 11454944
references.citation: Aust N Z J Obstet Gynaecol. 2004 Aug;44(4):302-6
references.pmid: 15282000
references.citation: Acta Paediatr Suppl. 1994 Nov;404:40-6
references.pmid: 7531042
references.citation: Brain Res. 2001 Mar 9;894(1):154-6
references.pmid: 11245827
references.citation: Eur J Pharmacol. 1995 Apr 4;276(3):257-66
references.pmid: 7601211
references.citation: Pharmacol Biochem Behav. 1979 Jun;10(6):889-94
references.pmid: 482309
references.citation: Pharmacol Biochem Behav. 2006 Mar;83(3):465-79
references.pmid: 16626794
references.citation: J Addict Dis. 2010 Apr;29(2):245-58
references.pmid: 20407980
references.citation: Curr Neuropharmacol. 2008 Jun;6(2):125-50
references.pmid: 19305793
references.citation: Nurs Womens Health. 2007 Dec;11(6):558-67
references.pmid: 18088293
references.citation: Pharmacol Biochem Behav. 2003 Feb;74(3):649-56
references.pmid: 12543231
references.citation: Peptides. 2000 Jul;21(7):1141-6
references.pmid: 10998549
references.citation: Ann N Y Acad Sci. 1989;562:195-207
references.pmid: 2742277
references.citation: J Pharmacol Toxicol Methods. 1999 Oct;42(2):61-6
references.pmid: 10924887
references.citation: Brain Res. 2008 Mar 10;1198:132-40
references.pmid: 18262500
references.citation: Glia. 2008 Jul;56(9):1017-27
references.pmid: 18381654
references.citation: Dev Psychobiol. 1995 Mar;28(2):71-84
references.pmid: 8529786
references.citation: Psychopharmacology (Berl). 2010 Jun;210(2):295-302
references.pmid: 20369354
references.citation: Brain Res Bull. 1981 Oct;7(4):405-10
references.pmid: 6271349
references.citation: Mayo Clin Proc. 2009 Jul;84(7):613-24
references.pmid: 19567715
references.citation: Hippocampus. 2006;16(6):521-30
references.pmid: 16598705
references.citation: Eur J Pharmacol. 2001 Mar 2;414(2-3):211-4
references.pmid: 11239921
references.citation: Neurotoxicol Teratol. 1992 Jul-Aug;14(4):265-71
references.pmid: 1326078
references.citation: Neurobehav Toxicol Teratol. 1984 Jul-Aug;6(4):271-5
references.pmid: 6392916
references.citation: Anat Cell Biol. 2012 Jun;45(2):121-7
references.pmid: 22822467
references.citation: Int J Neuropsychopharmacol. 2003 Sep;6(3):253-65
references.pmid: 12974992
references.citation: Glia. 2012 Jan;60(1):125-36
references.pmid: 22002899
references.citation: Brain Res Dev Brain Res. 1998 Nov 1;111(1):35-42
references.pmid: 9804882
references.citation: Mol Pain. 2013 Sep 08;9:45
references.pmid: 24010861
references.citation: J Addict Med. 2007 Jun;1(2):68-72
references.pmid: 21768937
references.citation: Child Care Health Dev. 2008 Jan;34(1):71-6
references.pmid: 18171447
references.citation: Brain Res Dev Brain Res. 2004 Jul 19;151(1-2):149-57
references.pmid: 15246701
references.citation: J Biomed Sci. 2010 Jun 07;17:46
references.pmid: 20529288
references.citation: Neuropharmacology. 1999 Aug;38(8):1207-23
references.pmid: 10462133
references.citation: Addict Biol. 2014 Jul;19(4):676-86
references.pmid: 23551991
references.citation: Eur J Pharmacol. 2011 Mar 5;654(2):166-72
references.pmid: 21147096
references.citation: Peptides. 2007 Jun;28(6):1229-39
references.pmid: 17499882
references.citation: Pharmacol Biochem Behav. 1996 Dec;55(4):615-8
references.pmid: 8981592
references.citation: Biull Eksp Biol Med. 1994 Aug;118(8):154-6
references.pmid: 7949036
references.citation: Eur J Obstet Gynecol Reprod Biol. 2009 Feb;142(2):119-23
references.pmid: 19058904
references.citation: Acta Paediatr Suppl. 1994 Nov;404:36-9
references.pmid: 7531041
references.citation: J Neurosci. 2004 Mar 24;24(12):2953-62
references.pmid: 15044534
references.citation: J Mol Neurosci. 2013 May;50(1):58-69
references.pmid: 22864979
references.citation: Neuroreport. 2003 Feb 10;14(2):239-42
references.pmid: 12598737
references.citation: Peptides. 2004 Aug;25(8):1355-63
references.pmid: 15350704
references.citation: NIDA Res Monogr. 1985;59:73-83
references.pmid: 3929135
references.citation: Nihon Shinkei Seishin Yakurigaku Zasshi. 2005 Oct;25(5):221-5
references.pmid: 16313098
references.citation: Pediatrics. 1997 Jul;100(1):79-83
references.pmid: 9200364
references.citation: Acta Obstet Gynecol Scand. 2007;86(2):185-90
references.pmid: 17364281
references.citation: Curr Neuropharmacol. 2004 Oct;2(4):395-402
references.pmid: 18997874
references.citation: Pain Physician. 2008 Mar;11(2 Suppl):S133-53
references.pmid: 18443637
references.citation: Hippocampus. 2009 Jul;19(7):649-57
references.pmid: 19115391