Prenatal exposure to methadone or buprenorphine alters µ‐opioid receptor binding and downstream signaling in the rat brain

Kongstorp, Mette; Bogen, Inger Lise; Steinsland, Synne; Nerem, Elisabeth; Salih, Triske Woshyar; Stiris, Tom; Andersen, Jannike Mørch

doi:10.1002/jdn.10043

Cited by 16 publications

(12 citation statements)

References 66 publications

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“…As such, the endogenous opioid system is implicated in both the acute and chronic effects of many rewarding substances. Using ligand binding and autoradiographic experiments, many studies indicate MOR densities and binding affinities are reduced across the whole brain and in the cortex, striatum, thalamus, hypothalamus, and amygdala of fetal and neonatal rodents with POE ( Wang et al, 1986 ; Tempel et al, 1988 , 1995 ; Darmani et al, 1992 ; Tempel and Espinoza, 1992 ; Belcheva et al, 1998 ; Chiou et al, 2003 ); however, this may recover during the first few weeks of life suggesting this may be an acute effect of POE or withdrawal from opioids ( Tempel et al, 1988 ; Kongstorp et al, 2020b ). In fact, studies in adult rodents indicate striatal MOR densities are actually upregulated in adulthood providing further support for the possibility that downregulation of MORs is a transient effect of POE ( Handelmann and Quirion, 1983 ; Vathy et al, 2003 ).…”

Section: Potential Molecular Mechanisms Underlying Altered Reward Behmentioning

confidence: 99%

Prenatal Opioid Exposure Enhances Responsiveness to Future Drug Reward and Alters Sensitivity to Pain: A Review of Preclinical Models and Contributing Mechanisms

Grecco

Atwood

2020

eNeuro

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The opioid crisis has resulted in an unprecedented number of neonates born with prenatal opioid exposure (POE); however, the long-term effects of POE on offspring behavior and neurodevelopment remain relatively unknown. The advantages and disadvantages of the various preclinical POE models developed over the last several decades are discussed in the context of clinical and translational relevance. Although considerable and important variability exists among preclinical models of POE, the examination of these preclinical models has revealed that opioid exposure during the prenatal period contributes to maladaptive behavioral development as offspring mature including an altered responsiveness to rewarding drugs and increased pain response. The present review summarizes key findings demonstrating the impact of POE on offspring drug selfadministration, drug consumption, the reinforcing properties of drugs, drug tolerance, and other reward-related behaviors such as hypersensitivity to pain. Potential underlying molecular mechanisms which may contribute this enhanced addictive phenotype in POE offspring are further discussed with special attention given to key brain regions associated with reward including the striatum, prefrontal cortex, ventral tegmental area, hippocampus, and amygdala. Improvements in preclinical models and further areas of study are also identified which may advance the translational value of findings and help address the growing problem of POE in clinical populations. Significance Statement As the number of the infants born following prenatal opioid exposure continues to increase, there is a greater need to employ preclinical models to study the potential consequences of POE and brain and behavioral development. A large body of evidence indicates POE is associated with alterations in reward-related behavior and molecular adaptations in reward neurocircuitry. This review seeks to: (1) provide an overview of the various types of preclinical models developed over the last few decades; (2) review the numerous behavioral studies examining drug-reward related behavior in offspring with POE; and (3) discuss potential contributing molecular mechanisms to this enhanced reward phenotype observed in POE offspring.

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Section: Potential Molecular Mechanisms Underlying Altered Reward Behmentioning

confidence: 99%

Prenatal Opioid Exposure Enhances Responsiveness to Future Drug Reward and Alters Sensitivity to Pain: A Review of Preclinical Models and Contributing Mechanisms

Grecco

Atwood

2020

eNeuro

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“…Experimental studies also confirmed that BUP and methadone caused cognitive impairment in rat offspring prenatally exposed to these drugs [7] , [8] , [9] . Several studies have also indicated that opioids may affect neurogenesis, cell proliferation, and myelination during brain development [10] , [11] , [12] .…”

Section: Introductionmentioning

confidence: 59%

Effects of exposure in utero to buprenorphine on oxidative stress and apoptosis in the hippocampus of rat pups

et al. 2022

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“…Opioid maintenance treatment (OMT) with buprenorphine has been sugested for women during pregnancy and lactation [1] , [2] . However, the developmental brain of neonates may be vulnerable to exogenous opioids [3] . OMT for pregnant women may be no threat for neonates, as opioids may exert through milk [4] .…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress and apoptotic index modifications in the hippocampus of rat pups born to mothers exposed to buprenorphine during lactation

et al. 2022

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Prenatal exposure to methadone or buprenorphine alters µ‐opioid receptor binding and downstream signaling in the rat brain

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 16 publications

References 66 publications

Prenatal Opioid Exposure Enhances Responsiveness to Future Drug Reward and Alters Sensitivity to Pain: A Review of Preclinical Models and Contributing Mechanisms

Prenatal Opioid Exposure Enhances Responsiveness to Future Drug Reward and Alters Sensitivity to Pain: A Review of Preclinical Models and Contributing Mechanisms

Effects of exposure in utero to buprenorphine on oxidative stress and apoptosis in the hippocampus of rat pups

Oxidative stress and apoptotic index modifications in the hippocampus of rat pups born to mothers exposed to buprenorphine during lactation

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