title: Delayed developmental changes in neonatal vocalizations correlates with variations in ventral medial hypothalamus and central amygdala development in the rodent infant: effects of prenatal cocaine.
abstract: While variations in neonatal distress vocalizations have long been shown to reflect the integrity of nervous system development following a wide range of prenatal and perinatal insults, a paucity of research has explored the neurobiological basis of these variations. To address this, virgin Sprague-Dawley rats were bred and divided into three groups: [1] untreated, [2] chronic-cocaine treated (30 mg/kg/day, gestation days (GDs) 1-20); or [3] chronic saline treated (2 mg/kg/day, GDs 1-20). Pregnant dams were injected with Bromodeoxyuridine (10 mg/kg) on GDs 13-15 to label proliferating cells in limbic regions of interest. Ultrasonic vocalizations (USVs) were recorded on postnatal days (PNDs) 1, 14, and 21, from one male and female pup per litter. Variations in acoustic properties of USVs following cocaine-exposure were age and sex-dependent including measures of total number, total duration and amplitude of USVs, and percent of USVs with at least one harmonic. Following USV testing brains were stained with standard fluorescent immunohistochemistry protocols and examined for variations in neuronal development and if variations were associated with acoustic characteristics. Limbic region developmental differences following cocaine-exposure were sex- and age-dependent with variations in the ventral medial hypothalamus and central amygdala correlating with variations in vocalizations on PND 14 and 21. Results suggest maturation of the ventral medial hypothalamus and central amygdala may provide the basis for variations in the sound and production of USVs. As vocalizations may serve as a neurobehavioral marker for nervous system integrity, understanding the neurobiological basis of neonatal vocalizations may provide the basis for early intervention strategies in high-risk infant populations.
authors.affiliation: University of North Carolina, Curriculum in Neurobiology, USA. elizabeth.cox@utah.edu
authors.forename: E T
authors.initials: ET
authors.lastname: Cox
authors.forename: C W
authors.initials: CW
authors.lastname: Hodge
authors.forename: M J
authors.initials: MJ
authors.lastname: Sheikh
authors.forename: A C
authors.initials: AC
authors.lastname: Abramowitz
authors.forename: G F
authors.initials: GF
authors.lastname: Jones
authors.forename: A W
authors.initials: AW
authors.lastname: Jamieson-Drake
authors.forename: P R
authors.initials: PR
authors.lastname: Makam
authors.forename: P S
authors.initials: PS
authors.lastname: Zeskind
authors.forename: J M
authors.initials: JM
authors.lastname: Johns
mesh_terms: D000161:Acoustic Stimulation; D000367:Age Factors; D000679:Amygdala / Q000254:growth & development / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D003042:Cocaine / Q000009:adverse effects*; D002658:Developmental Disabilities / Q000209:etiology / Q000473:pathology*; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects*; D005260:Female; D005583:Fourier Analysis; D005865:Gestational Age; D007033:Hypothalamus, Middle / Q000254:growth & development / Q000503:physiopathology*; D008297:Male; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013997:Time Factors; D014828:Vocalization, Animal / Q000502:physiology*
chemical_list: D018765:Dopamine Uptake Inhibitors; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine; D003042:Cocaine