Prenatal buprenorphine exposure decreases neurogenesis in rats

Wu, Chih-Cheng; Hung, Chih-Jen; Shen, Ching-Hui; Chen, Wenying; Chang, Chieh-Ming J.; Pan, Hung-Chuan; Liao, Su‐Lan; Chen, Chun‐Jung

doi:10.1016/j.toxlet.2013.12.001

Cited by 69 publications

(74 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…25 and intrauterine opioid exposure impairs neural tract development, 26 neurogensis, 27 myelination, 28 and neuronal longevity. 29 This emphasizes the importance of extending surveillance to at least school age for children after NAS as failure to diagnose and treat these conditions in a timely manner may lead to school difficulties, poor adult productivity, and psychological function.…”

Section: Figurementioning

confidence: 99%

Reasons for Rehospitalization in Children Who Had Neonatal Abstinence Syndrome

Uebel

Wright

Burns³

et al. 2015

Pediatrics

View full text Add to dashboard Cite

show abstract

Section: Figurementioning

confidence: 99%

Reasons for Rehospitalization in Children Who Had Neonatal Abstinence Syndrome

Uebel

Wright

Burns³

et al. 2015

Pediatrics

View full text Add to dashboard Cite

show abstract

“…Few have exposed rodents to prenatal opioids other than morphine. [23][24][25][26][27][28][29] Here, we describe a novel model of perinatal fentanyl exposure by administering fentanyl in the drinking water of pregnant mouse dams until litters are weaned at postnatal day 21. This protocol resembles the entire human gestational period 30 and demonstrates its face validity to the human condition, in that it results in postnatal, adolescent and adult phenotypes reminiscent of those in exposed humans.…”

mentioning

confidence: 99%

Enduring consequences of perinatal fentanyl exposure in mice

Alipio

Brockett

Fox

et al. 2019

Preprint

View full text Add to dashboard Cite

Opioid use by pregnant women is an understudied consequence associated with the opioid epidemic, resulting in a rise in the incidence of neonatal opioid withdrawal syndrome (NOWS), and lifelong neurobehavioral deficits that result from perinatal opioid exposure. There are few preclinical models that accurately recapitulate human perinatal drug exposure, and few focus on fentanyl, a potent synthetic opioid that is a leading driver of the opioid epidemic. To investigate the consequences of perinatal opioid exposure, we administered fentanyl to mouse dams in their drinking water throughout gestation and until litters were weaned at postnatal day (PD) 21. Fentanyl-exposed dams delivered smaller litters, and had higher litter mortality rates compared to controls.Metrics of maternal care behavior were not affected by the treatment, nor were there differences in dams' weight or liquid consumption throughout gestation and 21 days postpartum. Twenty-four hours after weaning and drug cessation, perinatal fentanyl-exposed mice exhibited signs of spontaneous somatic withdrawal behavior, and sex-specific weight fluctuations that normalized in adulthood. At adolescence (PD 35) they displayed elevated anxiety-like behaviors and decreased grooming, assayed in the elevated plus maze and sucrose splash tests. Finally, by adulthood (PD 55) they displayed impaired performance in a two-tone auditory discrimination task. Collectively, our findings suggest that perinatal fentanyl exposed mice exhibit somatic withdrawal behavior and changes across the lifespan reminiscent of humans born with NOWS.Within this growing crisis, individuals between the age of 18 and 25 have exhibited the largest increase in illicit opioid use (Substance Abuse and Mental Health Services Administration, 2013). It is concerning that women of reproductive age show increased incidence of use, given that opioids -both natural and synthetic -can readily cross the placenta and the blood-brain barrier. Indeed, in utero opioid exposure is associated with deleterious effects in developing offspring, with more dramatic effects on neurological function observed in infants relative to adults. 3 There has been an exponential increase in the distribution of the synthetic opioid, fentanyl, which is routinely incorporated into frequently used narcotics, such as heroin. 4 Fentanyl is 50 to 100 times more potent than morphine and is chiefly responsible for the recent increase in synthetic opioid-related overdose deaths. 5 The effects that synthetic opioids have on the developmental trajectory of offspring have been incompletely studied, and are critically needed to develop effective treatment and prevention plans.Women who used opioids during pregnancy have an increased rate of undergoing premature birth, stillbirth, and infant death. 6 Withdrawal symptoms occur in 30-80% of neonates exposed to opioids in utero, 7 and they exhibit decreased birth weight and body size. 8 Consequences may be long lasting, as children and adolescents exposed to pre and peri-natal opioids have disr...

show abstract

“…51 Behavioral effects, such as decreased levels of serotonin and brain-derived neurotrophic factor (BDNF), resulted in depression-like behavior in pups. 52,53 In addition to lower levels, the pups in both studies exhibited a longer immobility time for a swimming test and tail suspension test, which are commonly used for a depressive measurement in rats. The authors concluded that although the cause of depression in humans is not clear, decreased BDNF and serotonin levels may play a role.…”

Section: Behavioral Developmental and Biological Effects In Animal mentioning

confidence: 97%

“…Likewise, opioid agonists given to male rats prior to conception adversely affected behavioral and survival outcomes of future pups . Behavioral effects, such as decreased levels of serotonin and brain‐derived neurotrophic factor (BDNF), resulted in depression‐like behavior in pups . In addition to lower levels, the pups in both studies exhibited a longer immobility time for a swimming test and tail suspension test, which are commonly used for a depressive measurement in rats.…”

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

View full text Add to dashboard Cite

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.

show abstract

Prenatal buprenorphine exposure decreases neurogenesis in rats

Cited by 69 publications

References 51 publications

Reasons for Rehospitalization in Children Who Had Neonatal Abstinence Syndrome

Reasons for Rehospitalization in Children Who Had Neonatal Abstinence Syndrome

Enduring consequences of perinatal fentanyl exposure in mice

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

Contact Info

Product

Resources

About