Dose-dependent effects of morphine exposure on mRNA and microRNA (miR) expression in hippocampus of stressed neonatal mice

Morphine is used to sedate critically ill infants to treat painful or stressful conditions associated with intensive care. Whether neonatal morphine exposure affects microRNA (miR) expression and thereby alters mRNA regulation is unknown. We tested the hypothesis that repeated morphine treatment in...

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Bibliographic Details
Published in:PloS one 2015-04, Vol.10 (4), p.e0123047-e0123047
Main Authors: McAdams, Ryan M, McPherson, Ronald J, Beyer, Richard P, Bammler, Theo K, Farin, Frederico M, Juul, Sandra E
Format: Article
Language:English
Subjects:
Analgesics, Opioid - administration & dosage
Analgesics, Opioid - pharmacology
Analysis
Animal tissues
Animals
Animals, Newborn
Aquaporin 1
Argipressin
Calcium-binding protein
Calmodulin
Cell cycle
Cell death
Dosage and administration
Dose-Response Relationship, Drug
Exposure
Gene expression
Gene Expression Profiling - methods
Gene Expression Regulation - drug effects
Gene regulation
Gene set enrichment analysis
Genes
Hippocampus
Hippocampus - drug effects
Hippocampus - metabolism
Hypoxia
Immune response
Immune system
Infants
Messenger RNA
Metabolism
Mice
MicroRNA
MicroRNAs - genetics
miRNA
Morphine
Morphine - administration & dosage
Morphine - pharmacology
Neonates
Neurotransmission
Newborn babies
Pituitary hormones
Ribonucleic acid
RNA
RNA, Messenger - genetics
Signaling
Stress, Physiological - drug effects
Stress, Psychological - genetics
Stress, Psychological - pathology
Sulfates
Transcription
Vasopressin
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Summary:Morphine is used to sedate critically ill infants to treat painful or stressful conditions associated with intensive care. Whether neonatal morphine exposure affects microRNA (miR) expression and thereby alters mRNA regulation is unknown. We tested the hypothesis that repeated morphine treatment in stress-exposed neonatal mice alters hippocampal mRNA and miR expression. C57BL/6 male mice were treated from postnatal day (P) 5 to P9 with morphine sulfate at 2 or 5 mg/kg ip twice daily and then exposed to stress consisting of hypoxia (100% N2 1 min and 100% O2 5 min) followed by 2h maternal separation. Control mice were untreated and dam-reared. mRNA and miR expression profiling was performed on hippocampal tissues at P9. Overall, 2 and 5 mg/kg morphine treatment altered expression of a total of 150 transcripts (>1.5 fold change, P
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0123047