title: Impaired contextual fear extinction and hippocampal synaptic plasticity in adult rats induced by prenatal morphine exposure.
abstract: Prenatal opiate exposure causes a series of neurobehavioral disturbances by affecting brain development. However, the question of whether prenatal opiate exposure increases vulnerability to memory-related neuropsychiatric disorders in adult offspring remains largely unknown. Here, we found that rats prenatally exposed to morphine (PM) showed impaired acquisition but enhanced maintenance of contextual fear memory compared with control animals that were prenatally exposed to saline (PS). The impairment of acquisition was rescued by increasing the intensity of footshocks (1.2 mA rather than 0.8 mA). Meanwhile, we also found that PM rats exhibited impaired extinction of contextual fear, which is associated with enhanced maintenance of fear memory. The impaired extinction lasted for 1 week following extinction training. Furthermore, PM rats exhibited reduced anxiety-like behavior in the elevated plus-maze and light/dark box test without differences in locomotor activity. These alterations in PM rats were mirrored by abnormalities in synaptic plasticity in the Schaffer collateral-CA1 synapses of the hippocampus in vivo. PS rats showed blocked long-term potentiation and enabled long-term depression in CA1 synapses following contextual fear conditioning, while prenatal morphine exposure restricted synaptic plasticity in CA1 synapses. The smaller long-term potentiation in PM rats was not further blocked by contextual fear conditioning, and the long-term depression enabled by contextual fear conditioning was abolished. Taken together, our results provide the first evidence suggesting that prenatal morphine exposure may increase vulnerability to fear memory-related neuropsychiatric disorders in adulthood.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, Laboratory of Learning and Memory, Kunming Institute of Zoology, The Chinese Academy of Sciences, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, China.
authors.forename: Ji-Wei
authors.initials: JW
authors.lastname: Tan
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, Laboratory of Learning and Memory, Kunming Institute of Zoology, The Chinese Academy of Sciences, China.|School of Life Sciences, University of Science and Technology of China, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Duan
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, Laboratory of Learning and Memory, Kunming Institute of Zoology, The Chinese Academy of Sciences, China.
authors.forename: Qi-Xin
authors.initials: QX
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, Laboratory of Learning and Memory, Kunming Institute of Zoology, The Chinese Academy of Sciences, China.|School of Life Sciences, Anhui University, China.
authors.forename: Ze-Yang
authors.initials: ZY
authors.lastname: Ding
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, Laboratory of Learning and Memory, Kunming Institute of Zoology, The Chinese Academy of Sciences, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Jing
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, Laboratory of Learning and Memory, Kunming Institute of Zoology, The Chinese Academy of Sciences, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, Laboratory of Learning and Memory, Kunming Institute of Zoology, The Chinese Academy of Sciences, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, Laboratory of Learning and Memory, Kunming Institute of Zoology, The Chinese Academy of Sciences, China.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Mao
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, Laboratory of Learning and Memory, Kunming Institute of Zoology, The Chinese Academy of Sciences, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000517:prevention & control; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear / Q000187:drug effects* / Q000523:psychology; D005260:Female; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009473:Neuronal Plasticity / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000523:psychology
chemical_list: D009294:Narcotics; D009020:Morphine
keywords: Contextual fear conditioning; extinction; long-term depression; long-term potentiation; prenatal morphine exposure