A Novel Strategy for Attenuating Opioid Withdrawal in Neonates
Giovanni C Santoro1, Samarth Shukla1,2, Krishna Patel1, Jakub Kaczmarzyk1, Stergiani Agorastos1, Sandy Scherrer1, Yoon Young Choi1, Christina Veith1, Joseph Carrion1,3, Rebecca Silverman1, Danielle Mullin1, Mohamed Ahmed2, Wynne K Schiffer4, Jonathan D Brodie5 and Stephen L Dewey1,3,5*
- *Corresponding Author:
- Stephen L Dewey
Investigator and Director, Center for Neurosciences
Laboratory for Behavioural and Molecular Neuroimaging
Feinstein Institute for Medical Research, Manhasset, USA
E-mail: [email protected]
Received date: July 06, 2016; Accepted date: Aug 04, 2016; Published date: Aug 11, 2016
Citation: Santoro GC, Shukla S, Patel K, Kaczmarzyk J, Agorastos S, et al. (2016) A Novel Strategy for Attenuating Opioid Withdrawal in Neonates. J Addict Res Ther 7:291. doi:10.4172/2155-6105.1000291
Copyright: © 2016 Santoro GC, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.