title: NeuroD modulates opioid agonist-selective regulation of adult neurogenesis and contextual memory extinction.
abstract: Addictive drugs, including opioids, modulate adult neurogenesis. In order to delineate the probable implications of neurogenesis on contextual memory associated with addiction, we investigated opioid agonist-selective regulation of neurogenic differentiation 1 (NeuroD) activities under the conditioned place preference (CPP) paradigm. Training mice with equivalent doses of morphine and fentanyl produced different CPP extinction rates without measurable differences in the CPP acquisition rate or magnitude. Fentanyl-induced CPP required much longer time for extinction than morphine-induced CPP. We observed a parallel decrease in NeuroD activities and neurogenesis after morphine-induced CPP, but not after fentanyl-induced CPP. Increasing NeuroD activities with NeuroD-lentivirus (nd-vir) injection at the dentate gyrus before CPP training reversed morphine-induced decreases in NeuroD activities and neurogenesis, and prolonged the time required for extinction of morphine-induced CPP. On the other hand, decreasing NeuroD activities via injection of miRNA-190-virus (190-vir) reversed the fentanyl effect on NeuroD and neurogenesis and shortened the time required for extinction of fentanyl-induced CPP. Another contextual memory task, the Morris Water Maze (MWM), was affected similarly by alteration of NeuroD activities. The reduction in NeuroD activities either by morphine treatment or 190-vir injection decreased MWM task retention, while the increase in NeuroD activities by nd-vir prolonged MWM task retention. Thus, by controlling NeuroD activities, opioid agonists differentially regulate adult neurogenesis and subsequent contextual memory retention. Such drug-related memory regulation could have implications in eventual context-associated relapse.
authors.affiliation: Key Laboratory of Regenerative Biology of CAS, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Guangzhou, China. zheng_hui@gibh.ac.cn
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Horace H
authors.initials: HH
authors.lastname: Loh
authors.forename: Ping-Yee
authors.initials: PY
authors.lastname: Law
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D000089622:Doublecortin Domain Proteins; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005283:Fentanyl / Q000494:pharmacology; D016086:Lentivirus / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009020:Morphine / Q000008:administration & dosage*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: D000701:Analgesics, Opioid; D051792:Basic Helix-Loop-Helix Proteins; D000089622:Doublecortin Domain Proteins; D005283:Fentanyl; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; D009020:Morphine; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C546705:MIRN190 microRNA, mouse; C093564:Neurogenic differentiation factor 1