title: Delayed extinction and stronger drug-primed reinstatement of methamphetamine seeking in rats prenatally exposed to morphine.
abstract: Prenatal morphine (PM) affects the development of brain reward system and cognitive function. The present study aimed to determine whether PM exposure increases the vulnerability to MA addiction. Pregnant Sprague-Dawley rats were administered saline or morphine during embryonic days 3-20. The acquisition, extinction and reinstatement of methamphetamine (MA) conditioned place preference (CPP) and intravenous self-administration (SA) paradigms were assessed in the male adult offspring. There was no difference in the acquisition and expression of MA CPP between saline- and PM-exposed rats, whereas PM-exposed rats exhibited slower extinction and greater MA priming-induced reinstatement of drug-seeking behavior than controls. Similarly, MA SA under progressive ratio and fixed ratio schedules was not affected by PM exposure, but PM-exposed rats required more extinction sessions to reach the extinction criteria and displayed more severe MA priming-, but not cue-induced, reinstatement. Such alterations in extinction and reinstatement were not present when PM-exposed rats were tested in an equivalent paradigm assessing operant responding for food pellets. Our results demonstrate that PM exposure did not affect the association memory formation during acquisition of MA CPP or SA, but impaired extinction learning and increased MA-primed reinstatement in both tasks. These findings suggest that the offspring of women using morphine or heroin during pregnancy might predict persistent MA seeking during extinction and enhanced propensity to MA relapse although they might not be more susceptible to the reinforcing effect of MA during initiation of drug use.
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan.
authors.forename: Ying-Ling
authors.initials: YL
authors.lastname: Shen
authors.affiliation: Master Program/PhD Program in Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien 97004, Taiwan; Department of Psychiatry, Tzu Chi General Hospital, 707, Section 3, Chung-Yang Road, Hualien 97004, Taiwan.
authors.forename: Shao-Tsu
authors.initials: ST
authors.lastname: Chen
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan.
authors.forename: Tzu-Yi
authors.initials: TY
authors.lastname: Chan
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan.
authors.forename: Tsai-Wei
authors.initials: TW
authors.lastname: Hung
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan.
authors.forename: Pao-Luh
authors.initials: PL
authors.lastname: Tao
authors.affiliation: Institute of Neuroscience, National Cheng-Chi University, 64, Sec. 2, ZhiNan Road, Wenshan District, Taipei City 11605, Taiwan; Department of Psychology, National Cheng-Chi University, 64, Sec. 2, ZhiNan Road, Wenshan District, Taipei City 11605, Taiwan; Research Center for Mind, Brain and Learning, National Cheng-Chi University, 64, Sec. 2, ZhiNan Road, Wenshan District, Taipei City 11605, Taiwan.
authors.forename: Ruey-Ming
authors.initials: RM
authors.lastname: Liao
authors.affiliation: Institute of Neuroscience, National Cheng-Chi University, 64, Sec. 2, ZhiNan Road, Wenshan District, Taipei City 11605, Taiwan; Research Center for Mind, Brain and Learning, National Cheng-Chi University, 64, Sec. 2, ZhiNan Road, Wenshan District, Taipei City 11605, Taiwan.
authors.forename: Ming-Huan
authors.initials: MH
authors.lastname: Chan
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan; Master Program/PhD Program in Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien 97004, Taiwan; Institute of Neuroscience, National Cheng-Chi University, 64, Sec. 2, ZhiNan Road, Wenshan District, Taipei City 11605, Taiwan. Electronic address: hwei@nhri.org.tw.
authors.forename: Hwei-Hsien
authors.initials: HH
authors.lastname: Chen
mesh_terms: D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects*; D005260:Female; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D009020:Morphine / Q000008:administration & dosage*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000523:psychology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008694:Methamphetamine; D009020:Morphine
keywords: Conditioned place preference; Extinction; Methamphetamine; Progressive ratio; Reinstatement; Self-administration