Dataset Information

N-acetylcysteine mitigates acute opioid withdrawal behaviors and CNS oxidative stress in neonatal rats.

ABSTRACT:

Background

Neonatal abstinence syndrome (NAS) is a significant problem. Opioid withdrawal induces oxidative stress and disrupts glutamate and glutathione homeostasis. We hypothesized that N-acetylcysteine (NAC) administered during acute opioid withdrawal in neonatal rats would decrease withdrawal behaviors and normalize CNS glutathione and glutamate.

Methods

Osmotic minipumps with methadone (opioid dependent, OD) and saline (Sham) were implanted into Sprague Dawley dams 7 days prior to delivery. Pups were randomized to receive either naloxone plus saline or NAC (50-100?mg/kg), administered on postnatal day (PND) 7. We performed MR spectroscopy on PND6-7 before, 30?min, and 120?min after withdrawal. On PND7, we assessed withdrawal behaviors for 90?min after naloxone administration and summed scores during peak withdrawal period.

Results

Mean summed behavioral scores were significantly different between groups (?² (2)?=?10.49, p?=?0.005) but not different between NAC/NAL/OD and Sham (p?=?0.14): SAL/NAL/OD?=?17.2?±?4.2 (n?=?10); NAC/NAL/OD?=?11.3?±?5.6 (n?=?9); Sham?=?6.5?±?0.6 (n?=?4). SAL/NAL/OD pups had decreased glutathione at 120?min (p?=?0.01), while NAC/NAL/OD pups maintained pre-withdrawal glutathione (p?=?0.26).

Conclusion

In antenatal OD, NAC maintains CNS glutathione and mitigates acute opioid withdrawal in neonatal rats. This is the first study to demonstrate acute opioid withdrawal neurochemical changes in vivo in neonatal OD. NAC is a potential novel treatment for NAS.

SUBMITTER: Ward P

PROVIDER: S-EPMC7326708 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

N-acetylcysteine mitigates acute opioid withdrawal behaviors and CNS oxidative stress in neonatal rats.

Ward Price P Moss Hunter G HG Brown Truman R TR Kalivas Peter P Jenkins Dorothea D DD

Pediatric research 20200114 1

<h4>Background</h4>Neonatal abstinence syndrome (NAS) is a significant problem. Opioid withdrawal induces oxidative stress and disrupts glutamate and glutathione homeostasis. We hypothesized that N-acetylcysteine (NAC) administered during acute opioid withdrawal in neonatal rats would decrease withdrawal behaviors and normalize CNS glutathione and glutamate.<h4>Methods</h4>Osmotic minipumps with methadone (opioid dependent, OD) and saline (Sham) were implanted into Sprague Dawley dams 7 days pri ...[more]

PMID: 31935745

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Project description:The opioid epidemic in the United States has led to a significant increase in the incidence of neonatal opioid withdrawal syndrome (NOWS); however, the understanding of long-term consequences of NOWS is limited. The objective of this study was to evaluate post-discharge healthcare utilization in infants with NOWS and examine the association between NOWS severity and healthcare utilization. A retrospective cohort design was used to ascertain healthcare utilization in the first year after birth-related discharge using the CERNER Health Facts® database. ICD-9/ICD-10 diagnostic codes were used to identify live births and to classify infants into two study groups: NOWS and uncomplicated births (a 25% random sample). Evaluated outcomes included rehospitalization, emergency department (ED) visits within 30-days and one-year after discharge, and a composite one-year utilization event (either hospitalization or emergency department visit during that year). NOWS severity was operationalized as pharmacologic treatment, length of hospitalization, and medical conditions often associated with NOWS. In 3,526 infants with NOWS (restricted to gestational age ≥ 33 weeks), NOWS severity was associated with an increase in composite one-year utilization (OR: 1.1; 95% CI: 1.04-1.2) after adjusting for prematurity, sepsis, jaundice, use of antibiotics, infant sex, insurance status, race, hospital bed size, year of birth, and census division. In a subset of full-term infants (3008 with NOWS and 88,452 uncomplicated births), having a NOWS diagnosis was associated with higher odds of a 30-day (OR: 1.6; 95% CI: 1.03-2.4) and one-year rehospitalization (OR: 1.6; 95% CI: 1.1-2.4) after adjusting for infant sex, race, type of medical insurance, hospital location, census division, year of primary encounter, hospital bed size, and medical conditions. This study found higher healthcare utilization during the first year of life in infants diagnosed with NOWS, especially those with severe NOWS. Findings suggest a need for closer post-discharge follow-up and management of infants with NOWS.

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Dataset Information

N-acetylcysteine mitigates acute opioid withdrawal behaviors and CNS oxidative stress in neonatal rats.

Background

Methods

Results

Conclusion

Publications

N-acetylcysteine mitigates acute opioid withdrawal behaviors and CNS oxidative stress in neonatal rats.

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