title: 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 in18FDG 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.
authors.affiliation: Center for Neurosciences, Laboratory for Molecular and Behavioural Neuroimaging, Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Giovanni C
authors.initials: GC
authors.lastname: Santoro
authors.affiliation: Center for Neurosciences, Laboratory for Molecular and Behavioural Neuroimaging, Feinstein Institute for Medical Research, Manhasset, NY, USA; Division of Neonatal-Perinatal Medicine, Cohen Children's Medical Center of NY, New Hyde Park, NY, USA.
authors.forename: Samarth
authors.initials: S
authors.lastname: Shukla
authors.affiliation: Center for Neurosciences, Laboratory for Molecular and Behavioural Neuroimaging, Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Patel
authors.affiliation: Center for Neurosciences, Laboratory for Molecular and Behavioural Neuroimaging, Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Jakub
authors.initials: J
authors.lastname: Kaczmarzyk
authors.affiliation: Center for Neurosciences, Laboratory for Molecular and Behavioural Neuroimaging, Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Stergiani
authors.initials: S
authors.lastname: Agorastos
authors.affiliation: Center for Neurosciences, Laboratory for Molecular and Behavioural Neuroimaging, Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Scherrer
authors.affiliation: Center for Neurosciences, Laboratory for Molecular and Behavioural Neuroimaging, Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Yoon Young
authors.initials: YY
authors.lastname: Choi
authors.affiliation: Center for Neurosciences, Laboratory for Molecular and Behavioural Neuroimaging, Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Veith
authors.affiliation: Center for Neurosciences, Laboratory for Molecular and Behavioural Neuroimaging, Feinstein Institute for Medical Research, Manhasset, NY, USA; Department of Molecular Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Carrion
authors.affiliation: Center for Neurosciences, Laboratory for Molecular and Behavioural Neuroimaging, Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Silverman
authors.affiliation: Center for Neurosciences, Laboratory for Molecular and Behavioural Neuroimaging, Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Mullin
authors.affiliation: Division of Neonatal-Perinatal Medicine, Cohen Children's Medical Center of NY, New Hyde Park, NY, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ahmed
authors.affiliation: Department of Neurology, N. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Wynne K
authors.initials: WK
authors.lastname: Schiffer
authors.affiliation: Psychiatry Department, New York University School of Medicine, NY, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Brodie
authors.affiliation: Center for Neurosciences, Laboratory for Molecular and Behavioural Neuroimaging, Feinstein Institute for Medical Research, Manhasset, NY, USA; Department of Molecular Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, USA; Psychiatry Department, New York University School of Medicine, NY, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Dewey
keywords: GABA; GVG; Neonatal abstinence syndrome; PET imaging; Prenatal intervention; Vigabatrin; Withdrawal behaviour