A Novel Strategy for Attenuating Opioid Withdrawal in Neonates

Abstract

The rate of Neonatal Abstinence Syndrome (NAS) has drastically increased over the past decade. The average hospital expense per NAS patient has tripled, while the number of babies born to opioid-dependent mothers has increased to 5 in 1000 births. Current treatment options are limited to opioid replacement and tapering. Consequently, we examined the efficacy of prenatal, low-dose and short-term vigabatrin (γ-vinyl GABA, GVG) exposure for attenuating these symptoms as well as the metabolic changes observed in the brains of these animals upon reaching adolescence. Pregnant Sprague-Dawley rats were treated in one of four ways: 1) saline; 2) morphine alone; 3) morphine+GVG at 25 mg/kg; 4) morphine+GVG at 50 mg/kg. Morphine was administered throughout gestation, while GVG administration occurred only during the last 5 days of gestation. On post-natal day 1, naloxone-induced withdrawal behaviours were recorded in order to obtain a gross behaviour score. Approximately 28 days following birth, 18FDG microPET scans were obtained on these same animals (Groups 1, 2, and 4). Morphine-treated neonates demonstrated significantly higher withdrawal scores than saline controls. However, GVG at 50 but not 25 mg/kg/day significantly attenuated them. Upon reaching adolescence, morphine treated animals showed regionally specific changes in 18FDG uptake. Again, prenatal GVG exposure blocked them. These data demonstrate that low-dose, short-term prenatal GVG administration blocks naloxone-induced withdrawal in neonates. Taken together, these preliminary findings suggest that GVG may provide an alternative and long-lasting pharmacologic approach for the management of neonatal and adolescent symptoms associated with NAS.

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

“…Methadone exposure continued via ad libitum breast milk 13,27,28 until postnatal days (PNDs) 6-7 when methadone-and salineexposed pups underwent acute or sham withdrawal, behavioral testing, and MRS. 26,[29][30][31] Acute precipitated withdrawal In Experiment 1, to establish the model and validate the behavioral scoring, pups were randomized within litter to receive either naloxone hydrochloride (1 mg/kg, intraperitoneal (i.p. )), a dose that has been shown to precipitate acute withdrawal in rats, 26,[29][30][31] or an equal volume of saline. Treatment groups in Experiment 1 were Sham (pups with neither methadone exposure nor naloxone), SAL OD (pups with methadone exposure, opioid dependent, and saline but no naloxone), and NAL OD (methadone exposure, opioid dependent, and naloxone).…”

“…Adapted from Barr et al 29,33,34 N-acetylcysteine mitigates acute opioid withdrawal behaviors and CNS. .…”