Buprenorphine, methadone, and morphine treatment during pregnancy: behavioral effects on the offspring in rats

Chen, Hwei-Hsien; Chiang, Yang‐Jen; Yuan, Zung Fan; Kuo, Chung-Chih; Lai, Mei-Dan; Hung, Tsai-Wei; Ho, Ing-Kang; Chen, Shao-Tsu

doi:10.2147/ndt.s70585

Cited by 80 publications

(84 citation statements)

References 54 publications

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“…Thus, it seems that anxiety‐like behavior is increased in the male offspring of morphine‐exposed parents. In support of our data, previous studies have demonstrated that prenatal morphine exposure increases anxiety in EPM test in the F1 offspring (Chen et al, 2015).…”

Section: Discussionsupporting

confidence: 92%

“…In almost all the researches that have investigated the effect of parental morphine addiction on their offspring, the female rat was exposed to morphine either during the adolescent period (Byrnes et al, 2011, 2013) or in pregnancy (Riley and Vathy, 2006; Szutorisz et al, 2014; Chen et al, 2015; Shen et al, 2016). Adolescent period could affect the development of neural and endocrine systems, and pregnancy studies make the researcher unable to exclude the direct effects of morphine on the fetus.…”

Section: Introductionmentioning

confidence: 99%

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Adult rat morphine exposure changes morphine preference, anxiety, and the brain expression of dopamine receptors in male offspring

Vousooghi

Sadat‐Shirazi

Safavi

et al. 2018

Intl J of Devlp Neuroscience

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Addiction to drugs, including opioids is the result of an interplay between environmental and genetic factors. It has been shown that the progeny of addict people is at higher risk for drug addiction. However, the mechanisms of such trans-generational effects of drugs are not so clear. Here we have evaluated the effects of parental morphine consumption on anxiety, morphine preference, and mRNA expression of dopamine receptors in F1 and F2 male offspring. Morphine was chronically administered to adult male and female Wistar rats followed by 14-day abstinence before mating. Morphine preference and anxiety-like behavior in the offspring were measured by two-bottle-choice paradigm and elevated-plus maze, respectively. Real-time PCR was used to measure the mRNA expression level of dopamine receptors in the striatum, nucleus accumbens, prefrontal cortex, and hippocampus of F1 animals. The results indicated that F1 but not the F2 male progeny of morphine-exposed parents had a greater preference for morphine, and more anxiety-like behavior compared to the offspring of saline-treated parents. In F1 male progeny of morphine-treated parents, D1 and D5 dopamine receptors were significantly increased in the prefrontal cortex and nucleus accumbens. D5 and D2 receptors were decreased in the hippocampus. D4 dopamine receptor was augmented in striatum and hippocampus and decreased in the prefrontal cortex. Adulthood exposure to chronic morphine in male and female rats before conception leads to higher morphine preference and increased anxiety in F1 but not F2 male progeny. Alterations of dopamine receptor expression in the reward system may be one mechanism responsible for observed changes in F1 offspring.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Adult rat morphine exposure changes morphine preference, anxiety, and the brain expression of dopamine receptors in male offspring

Vousooghi

Sadat‐Shirazi

Safavi

et al. 2018

Intl J of Devlp Neuroscience

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“…Anxiety‐like behaviors have also been demonstrated with opioid agonists in animal studies. Prenatal exposure to opioids may alter learning and/or memory via the opioid receptor system . Reduced social behaviors may be associated with changes in μ‐opioid receptor function .…”

Section: Behavioral Developmental and Biological Effects In Animal mentioning

confidence: 99%

Methadone, Buprenorphine, and Naltrexone for the Treatment of Opioid Use Disorder in Pregnant Women

et al. 2017

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Pregnant women with opioid use disorder can be treated with methadone, buprenorphine, or naltrexone to reduce opioid use and improve retention to treatment. In this review, we compare the pregnancy outcomes of methadone, buprenorphine, and naltrexone in clinical trials and discuss the potential behavioral and developmental effects of these agents seen in offspring in animal studies. Important clinical considerations in the management of opioid use disorder in pregnant women and their infants are also discussed. Outside of pregnancy, buprenorphine is used in combination with naloxone to reduce opioid abuse and diversion. During pregnancy, however, the use of buprenorphine as a single agent is preferred to prevent prenatal naloxone exposure. Both methadone and buprenorphine are widely used to treat opioid use disorder; however, compared with methadone, buprenorphine is associated with shorter treatment duration, less medication needed to treat neonatal abstinence syndrome (NAS) symptoms, and shorter hospitalizations for neonates. Despite being the standard of care, medication-assisted treatment with methadone or buprenorphine is still underused, making it apparent that more options are necessary. Naltrexone is not a first-line treatment primarily because both detoxification and an opioid-free period are required. More research is needed to determine naltrexone safety and benefits in pregnant women. Animal studies suggest that changes in pain sensitivity, developmental processes, and behavioral responses may occur in children born to mothers receiving methadone, buprenorphine, or naltrexone and is an area that warrants future studies.

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“…194 In animal models both cognitive and behavioral effects of prenatal opioid exposure have been demonstrated. 195,196 The endogenous opioid system has been shown to be crucial in the control of oligodendrocyte function and myelination. 197 Interference with this system by maternal opioid use could thus alter the normal myelination process.…”

Section: Paper IIImentioning

confidence: 99%

Cerebral Magnetic Resonance Imaging in Children With Prenatal Drug Exposure

Sirnes

Elgen

Chong

et al. 2016

Clin Pediatr (Phila)

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This study aimed to evaluate cerebral magnetic resonance imaging (MRI) scans of children with prenatal drug exposure in a clinical context. A hospital-based cohort of 10- to 14-year-old children, prenatally exposed to alcohol, opioids, and polysubstances, and a group of sex- and age-matched controls were examined with cerebral MRI. Scans obtained from 34 exposed children and 40 controls were scored based on the presence and degree of pathology by an experienced pediatric neuroradiologist blinded to the participants’ background. Overall visual detectable MRI pathology was found in 35% of the exposed children and 33% of the controls (odds ratio = 1.08; 95% confidence interval = 0.36-3.25). No specific imaging pattern following prenatal drug exposure was seen by the means of simple visual analysis of cerebral MRI scans. Although cerebral MRI is feasible, it is probably of limited value in the clinical assessment of children with prenatal drug exposure.

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Buprenorphine, methadone, and morphine treatment during pregnancy: behavioral effects on the offspring in rats

Cited by 80 publications

References 54 publications

Adult rat morphine exposure changes morphine preference, anxiety, and the brain expression of dopamine receptors in male offspring

Adult rat morphine exposure changes morphine preference, anxiety, and the brain expression of dopamine receptors in male offspring

Methadone, Buprenorphine, and Naltrexone for the Treatment of Opioid Use Disorder in Pregnant Women

Cerebral Magnetic Resonance Imaging in Children With Prenatal Drug Exposure

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