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Neurobehavioral effects of neonatal opioid exposure in mice: Influence of the OPRM1 SNP
Author(s) -
Robinson Shivon A.,
Jones Alonzo D.,
Brynildsen Julia K.,
Ehrlich Michelle E.,
Blendy Julie A.
Publication year - 2020
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12806
Subject(s) - opioid , morphine , in utero , medicine , sensitization , pregnancy , single nucleotide polymorphism , snp , opioid receptor , endocrinology , physiology , anesthesia , genotype , fetus , biology , receptor , genetics , gene , immunology
Opioid use among pregnant women is a growing public health concern in the United States. Infants exposed to opioids in utero are at risk of exhibiting neonatal opioid withdrawal syndrome (NOWS). The biological mechanisms underlying short and long‐term consequences of in utero opioid exposure and NOWS are unknown. A potential genetic factor is a single‐nucleotide polymorphism (SNP) in the mu‐opioid receptor gene ( OPRM1 A118G). Opioid exposed infants with the G‐allele spend less time in hospitals after birth. To determine whether this SNP modulates the neurobehavioral effects of neonatal opioid exposure and withdrawal, we used mice possessing the equivalent Oprm1 SNP (A112G). Pups were treated chronically with saline or morphine from postnatal days (PNDs) 1 to 14, a developmental period equivalent to the third trimester of a human pregnancy and a sensitive period for opioid exposure in rodents. Morphine treatment produced significant developmental delays regardless of genotype and increased total ultrasonic vocalizations in males during spontaneous withdrawal. Animals were aged and tested for anxiety and drug response during adolescence and adulthood, respectively. AA morphine‐treated animals showed reduced activity in the marble burying task compared with saline controls; however, this effect was absent in AG and GG animals. As adults, AA males exposed to morphine from PNDs 1 to 14 exhibited enhanced development of locomotor sensitization to morphine, whereas females showed reduced locomotor sensitization. These data suggest the involvement of the Oprm1 SNP for certain outcomes of neonatal opioid exposure and highlight the importance of considering sex and genetic variability for the prognosis of NOWS.