PMID- 27392631 OWN - NLM STAT- MEDLINE DCOM- 20171212 LR - 20190318 IS - 1432-2072 (Electronic) IS - 0033-3158 (Linking) VI - 233 IP - 17 DP - 2016 Sep TI - Increased cocaine-induced conditioned place preference during periadolescence in maternally separated male BALB/c mice: the role of cortical BDNF, microRNA-212, and MeCP2. PG - 3279-88 LID - 10.1007/s00213-016-4373-z [doi] AB - RATIONALE: Early life stress is a major risk factor for cocaine addiction; however, the underlying molecular mechanisms remain relatively unexplored. MicroRNA-212 (miR-212) and methyl CpG binding protein 2 (MeCP2) have recently emerged as key regulators of brain-derived neurotrophic factor (BDNF) signaling during the acquisition and maintenance of cocaine-seeking behaviors. OBJECTIVES: We therefore investigated the effect of maternal separation (MS) on cocaine-induced conditioned place preference (CPP) during periadolescence and how this influences miR-212, Mecp2, and Bdnf expressions in the prefrontal cortex. METHODS: Male BALB/c mice subjected to MS (3 h/day) from postnatal day 2 to 15 or normal animal facility rearing (AFR) were tested for CPP at postnatal day 45, or not exposed to experimental manipulations (drug-naive animals). Cultured primary cortical neurons were used to determine miR-212 expression changes following depolarization by KCL treatment. RESULTS: MS increased cocaine-induced CPP and decreased Bdnf exon IV expression, which correlated with higher CPP scores in such animals. An experience-dependent decrease in miR-212 expression was observed following CPP test. This effect was mimicked in primary cortical neurons in vitro, under activity-dependent conditions. In contrast, increased Mecp2 expression was found after CPP test, suggesting an opposing relationship between miR-212 and Mecp2 expression following cocaine place preference acquisition. However, these effects were not present in mice exposed to MS. CONCLUSIONS: Together, our results suggest that early life stress can enhance the motivational salience for cocaine-paired cues during periadolescence, and that altered expression of miR-212, Mecp2, and Bdnf in the prefrontal cortex is involved in this process. FAU - Viola, Thiago Wendt AU - Viola TW AD - Postgraduate Program in Pediatrics and Child Health, Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. AD - Developmental Cognitive Neuroscience Lab (DCNL), Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS), Avenida Ipiranga, 6681, predio 11, sala 928, Porto Alegre, 90619-900, RS, Brazil. FAU - Wearick-Silva, Luis Eduardo AU - Wearick-Silva LE AD - Postgraduate Program in Pediatrics and Child Health, Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. AD - Developmental Cognitive Neuroscience Lab (DCNL), Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS), Avenida Ipiranga, 6681, predio 11, sala 928, Porto Alegre, 90619-900, RS, Brazil. FAU - De Azeredo, Lucas Araujo AU - De Azeredo LA AD - Developmental Cognitive Neuroscience Lab (DCNL), Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS), Avenida Ipiranga, 6681, predio 11, sala 928, Porto Alegre, 90619-900, RS, Brazil. AD - Postgraduate Program in Medicine and Health Sciences, PUCRS, Porto Alegre, RS, Brazil. FAU - Centeno-Silva, Anderson AU - Centeno-Silva A AD - Developmental Cognitive Neuroscience Lab (DCNL), Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS), Avenida Ipiranga, 6681, predio 11, sala 928, Porto Alegre, 90619-900, RS, Brazil. FAU - Murphy, Conor AU - Murphy C AD - Department of Pharmacology and Toxicology, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria. FAU - Marshall, Paul AU - Marshall P AD - Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California-Irvine, Irvine, 92697, CA, USA. FAU - Li, Xiang AU - Li X AD - Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California-Irvine, Irvine, 92697, CA, USA. FAU - Singewald, Nicolas AU - Singewald N AD - Department of Pharmacology and Toxicology, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria. FAU - Garcia, Frederico AU - Garcia F AD - Department of Psychiatry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. FAU - Bredy, Timothy W AU - Bredy TW AD - Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, University of California-Irvine, Irvine, 92697, CA, USA. AD - Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia. FAU - Grassi-Oliveira, Rodrigo AU - Grassi-Oliveira R AUID- ORCID: 0000-0001-9911-5921 AD - Postgraduate Program in Pediatrics and Child Health, Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. rodrigo.grassi@pucrs.br. AD - Developmental Cognitive Neuroscience Lab (DCNL), Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS), Avenida Ipiranga, 6681, predio 11, sala 928, Porto Alegre, 90619-900, RS, Brazil. rodrigo.grassi@pucrs.br. LA - eng PT - Journal Article DEP - 20160709 PL - Germany TA - Psychopharmacology (Berl) JT - Psychopharmacology JID - 7608025 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Dopamine Uptake Inhibitors) RN - 0 (MIRN212 microRNA, mouse) RN - 0 (Mecp2 protein, mouse) RN - 0 (Methyl-CpG-Binding Protein 2) RN - 0 (MicroRNAs) RN - I5Y540LHVR (Cocaine) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/drug effects/*genetics MH - Cocaine/*pharmacology MH - Cocaine-Related Disorders MH - Conditioning, Classical/*drug effects MH - Dopamine Uptake Inhibitors/*pharmacology MH - Male MH - *Maternal Deprivation MH - Methyl-CpG-Binding Protein 2/drug effects/*genetics MH - Mice MH - Mice, Inbred BALB C MH - MicroRNAs/drug effects/*metabolism MH - Prefrontal Cortex/drug effects/*metabolism OTO - NOTNLM OT - *Adolescence OT - *Brain-derived neurotrophic factor OT - *Cocaine OT - *Conditioned place preference OT - *Maternal separation OT - *microRNAs EDAT- 2016/07/10 06:00 MHDA- 2017/12/13 06:00 CRDT- 2016/07/10 06:00 PHST- 2016/02/11 00:00 [received] PHST- 2016/06/18 00:00 [accepted] PHST- 2016/07/10 06:00 [entrez] PHST- 2016/07/10 06:00 [pubmed] PHST- 2017/12/13 06:00 [medline] AID - 10.1007/s00213-016-4373-z [pii] AID - 10.1007/s00213-016-4373-z [doi] PST - ppublish SO - Psychopharmacology (Berl). 2016 Sep;233(17):3279-88. doi: 10.1007/s00213-016-4373-z. Epub 2016 Jul 9.